TERAPIA ANTIRRETROVIRAL EN SITUACIONES ESPECIALES
41
TERAPIA ANTIRRETROVIRAL EN SITUACIONES ESPECIALES VIGO, NOVIEMBRE 2019 Hernando Knobel Freud. Servicio de Enfermedades Infecciosas. Hospital del Mar. Barcelona.
Transcript of TERAPIA ANTIRRETROVIRAL EN SITUACIONES ESPECIALES
TERAPIA ANTIRRETROVIRAL EN SITUACIONES ESPECIALES
VIGO NOVIEMBRE 2019
Hernando Knobel Freud
Servicio de Enfermedades Infecciosas
Hospital del Mar Barcelona
PUNTOS A TRATAR
bull TAR en adolescentes
bull TAR en mujeres
bull TAR en pacientes socialmente vulnerables
bull TAR en pacientes ldquomayoresrdquo
TAR en adolescentesIntroduccioacuten
Adolescentes grupo de edad con mortalidad en ascenso Adolescentes infectados por transmisioacuten vertical (gt90)
Infeccioacuten perinatal
Infeccioacuten sintomaacutetica Pacientes ldquosupervivientesrdquo
Infeccioacuten VIH durante la adolescencia Infeccioacuten transmisioacuten sexual
Chicas relaciones heterosexuales
Chicos relaciones con hombres
Infeccioacuten transmisioacuten parenteral (drogas)
Nueva patologiacutea croacutenica
Adolescentesjoacutevenes diferencias seguacuten el tipo de transmisioacuten del VIH
bull Convivencia con el VIH desde al el nacimiento
bull Informacioacuten en pediatriacutea Mala aceptacioacuten
bull Alteraciones neurocognitivas
bull Fracaso escolar
bull TAR larga exposicioacuten Toxicidad TAR complejo
bull Comorbilidades
bull Historia de eventos sida
bull Necesidad de atencioacutensoporte psicoloacutegico
bull Consumo cannabis
bull Situacioacuten familiar compleja con frecuencia perdida de los padres
bull Dificultades para afrontar el futuro
bull Trabajo
bull Infeccioacuten VIH reciente (transmisioacuten sexual)
bull Informacioacuten en pediatriacutea o en Unidad Adultos
bull Dificultades de seguimiento
bull Reciente exposicioacuten al TAR TAR sencillo
bull Menos comorbilidades
bull No eventos sida
bull Necesidad de atencioacuten soporte psicoloacutegico
bull Tienen padres o estructura familiar no siempre
protectora
bull Dudas Planificacioacuten de futuro
Cambio fiacutesico y psicoloacutegico de la adolescencia incertidumbres
necesidad de informacioacuten en este nuevo periodo de desarrollo Miedo a la estigmatizacioacuten
Periodo de labilidad y necesidad de soporte al TAR reivindicacioacuten de sus derechos Necesidad del grupo
Infeccioacuten por transmisioacuten Vertical Infeccioacuten durante la adolescencia
Seguimiento complejo
Apoyo individualizado al cumplimiento
Informacioacuten y educacioacuten en relacioacuten a su
enfermedad
Soporte psicoloacutegico y social
Soporte de pares
Adolescentesjoacutevenes diferencias seguacuten el tipo de transmisioacuten del VIH
Paso-transferencia a la unidad de adultosGuiacuteas espantildeolas
bull La transicioacuten es un proceso individual complejo y difiacutecil en el que deben tenerse en cuenta aspectos meacutedicos psicosociales emocionales vocacionales y educacionales del paciente (AIII)
bull -La transicioacuten debe planificarse con el suficiente tiempo 2-3 antildeos no debieacutendose realizar la transicioacuten si el paciente se encuentra en una situacioacuten inestable(BIII)
bull -El equipo de pediatriacutea debe entrenar al paciente en autonomiacutea y conocimiento responsable de su infeccioacuten para que sepa asumir el cambio al sistema sanitario del adulto(AIII)
bull -El equipo de adultos debe conocer con tiempo la historia personal y meacutedica del adolescente a traveacutes de las reuniones mantenidas con el equipo pediaacutetrico asiacute como mediante un INFORMEelaborado desde pediatriacutea (CIII)
bull -La MONITORIZACION tras la transicioacuten deberiacutea realizarse al menos durante el primer antildeo para evitar peacuterdidas y fracaso de la misma (CIII)
wwwmsssigobesciudadanosenfLesionesenfTransmisiblessidapublicacionesprofSanitariosGuiaAdolescentes15Octubre2015pdf
Tratamiento ARV en adolescentes
bull Mayores problemas de adherencia
bull Cambios farmacocineacutetica Dosificacioacuten de los faacutermacos seguacuten desarrollo puberal
bull Estadio I y II Tanner dosificacioacuten pediaacutetrica
bull Estadio V dosificacioacuten ldquoadultosrdquo
bull Estadios III y IV pediaacutetricas o adultos
bull Adaptar e individualizar el tratamiento
bull Pautas de maacutes faacutecil cumplimiento
bull Preparados combinados STR
bull Tratamientos maacutes complejos bull Enfermedad avanzada acumulo de resistencias
bull Interacciones con otros faacutermacosbull Anticonceptivos Psicotropos Drogas
Resumen
bull Los adolescentes constituyen un grupo ldquominoritario y especialrdquo dentro de la poblacioacuten de pacientes con infeccioacuten VIH
bull La atencioacuten de los adolescentesadultos joacutevenes con infeccioacuten VIH por transmisioacuten vertical supone un reto
bull Riesgo de progresioacuten alto
bull Expuestos a un gran nuacutemero de ARV con fracaso terapeacuteutico frecuente
bull Mala adherencia
bull Peacuterdida de seguimiento
bull Los pacientes con mayor riesgo de progresioacuten son los que tienen mayor probabilidad de perderse tras ser transferidos a las
Unidades de adultos
bull La gestacioacuten la hospitalizacioacuten la presentacioacuten de infecciones oportunistas el ingreso en centros penitenciarios o de acogida
constituyen las causas maacutes frecuentes de reiniciar el seguimiento
bull Mientras que la negacioacuten de la enfermedad el consumo de toacutexicos los trastornos psiquiaacutetricos y la falta de soporte socio-familiar
constituyen las principales razones de abandono del seguimiento
MUJER Y VIH
iquestEXISTEN DIFERENCIAS
REALES ENTRE HOMBRES Y
MUJERES
SIhellip MUCHIacuteSIMAS
Solo desde la perspectiva de la infeccioacuten por VIH
Patogeacutenesis
Reservorio
PK-PD
Participacioacuten en ensayoscliacutenicos
Factores sociales
DIFERENCIAS DE SEXO RELACIONADAS CON EL TRATAMIENTO DEL VIH Y LA PROGRESIOacuteN DE
LA ENFERMEDAD
Female sex is associated with
Lower HIV viral load (JAIDS 20023111-19)
Higher CD4+ count (AIDS 1997111071-3)
More pronounced immune and vaccine responses (JAIDS 2011579-15)
Higher levels of immune activation (JID 2013208830-8)
More frequent ART side effects and discontinuation (J Antimicrob Chem
2007 60 724-32)
Conclusions
Gender inequalities in the response to cART are
mainly explained by the different prevalence of
socioeconomic characteristics in women compared
with men
Conclusions
It is essential to understand sex differences in
drug response as they may affect drug safety and
effectiveness
Conclusions
Women and men potentially differ in the course of
their HIV infection their response to treatment
and drug pharmacokinetics all of which are
compounded by social and behavioral factors
CASO CLIacuteNICO
bullJosefina 26 antildeos
Diagnosticada de infeccioacuten por VIH recientemente en analiacutetica rutinaria
iquestTAR a proponer
Analiacutetica
HBsAg negativo
Total anti-HBc negativo
HCV negativo
RPR (18)
PPD negative
HIV-RNA 83000 cpsmL
CD4 385 celsmm3
Examen fiacutesico sin alteraciones
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
PUNTOS A TRATAR
bull TAR en adolescentes
bull TAR en mujeres
bull TAR en pacientes socialmente vulnerables
bull TAR en pacientes ldquomayoresrdquo
TAR en adolescentesIntroduccioacuten
Adolescentes grupo de edad con mortalidad en ascenso Adolescentes infectados por transmisioacuten vertical (gt90)
Infeccioacuten perinatal
Infeccioacuten sintomaacutetica Pacientes ldquosupervivientesrdquo
Infeccioacuten VIH durante la adolescencia Infeccioacuten transmisioacuten sexual
Chicas relaciones heterosexuales
Chicos relaciones con hombres
Infeccioacuten transmisioacuten parenteral (drogas)
Nueva patologiacutea croacutenica
Adolescentesjoacutevenes diferencias seguacuten el tipo de transmisioacuten del VIH
bull Convivencia con el VIH desde al el nacimiento
bull Informacioacuten en pediatriacutea Mala aceptacioacuten
bull Alteraciones neurocognitivas
bull Fracaso escolar
bull TAR larga exposicioacuten Toxicidad TAR complejo
bull Comorbilidades
bull Historia de eventos sida
bull Necesidad de atencioacutensoporte psicoloacutegico
bull Consumo cannabis
bull Situacioacuten familiar compleja con frecuencia perdida de los padres
bull Dificultades para afrontar el futuro
bull Trabajo
bull Infeccioacuten VIH reciente (transmisioacuten sexual)
bull Informacioacuten en pediatriacutea o en Unidad Adultos
bull Dificultades de seguimiento
bull Reciente exposicioacuten al TAR TAR sencillo
bull Menos comorbilidades
bull No eventos sida
bull Necesidad de atencioacuten soporte psicoloacutegico
bull Tienen padres o estructura familiar no siempre
protectora
bull Dudas Planificacioacuten de futuro
Cambio fiacutesico y psicoloacutegico de la adolescencia incertidumbres
necesidad de informacioacuten en este nuevo periodo de desarrollo Miedo a la estigmatizacioacuten
Periodo de labilidad y necesidad de soporte al TAR reivindicacioacuten de sus derechos Necesidad del grupo
Infeccioacuten por transmisioacuten Vertical Infeccioacuten durante la adolescencia
Seguimiento complejo
Apoyo individualizado al cumplimiento
Informacioacuten y educacioacuten en relacioacuten a su
enfermedad
Soporte psicoloacutegico y social
Soporte de pares
Adolescentesjoacutevenes diferencias seguacuten el tipo de transmisioacuten del VIH
Paso-transferencia a la unidad de adultosGuiacuteas espantildeolas
bull La transicioacuten es un proceso individual complejo y difiacutecil en el que deben tenerse en cuenta aspectos meacutedicos psicosociales emocionales vocacionales y educacionales del paciente (AIII)
bull -La transicioacuten debe planificarse con el suficiente tiempo 2-3 antildeos no debieacutendose realizar la transicioacuten si el paciente se encuentra en una situacioacuten inestable(BIII)
bull -El equipo de pediatriacutea debe entrenar al paciente en autonomiacutea y conocimiento responsable de su infeccioacuten para que sepa asumir el cambio al sistema sanitario del adulto(AIII)
bull -El equipo de adultos debe conocer con tiempo la historia personal y meacutedica del adolescente a traveacutes de las reuniones mantenidas con el equipo pediaacutetrico asiacute como mediante un INFORMEelaborado desde pediatriacutea (CIII)
bull -La MONITORIZACION tras la transicioacuten deberiacutea realizarse al menos durante el primer antildeo para evitar peacuterdidas y fracaso de la misma (CIII)
wwwmsssigobesciudadanosenfLesionesenfTransmisiblessidapublicacionesprofSanitariosGuiaAdolescentes15Octubre2015pdf
Tratamiento ARV en adolescentes
bull Mayores problemas de adherencia
bull Cambios farmacocineacutetica Dosificacioacuten de los faacutermacos seguacuten desarrollo puberal
bull Estadio I y II Tanner dosificacioacuten pediaacutetrica
bull Estadio V dosificacioacuten ldquoadultosrdquo
bull Estadios III y IV pediaacutetricas o adultos
bull Adaptar e individualizar el tratamiento
bull Pautas de maacutes faacutecil cumplimiento
bull Preparados combinados STR
bull Tratamientos maacutes complejos bull Enfermedad avanzada acumulo de resistencias
bull Interacciones con otros faacutermacosbull Anticonceptivos Psicotropos Drogas
Resumen
bull Los adolescentes constituyen un grupo ldquominoritario y especialrdquo dentro de la poblacioacuten de pacientes con infeccioacuten VIH
bull La atencioacuten de los adolescentesadultos joacutevenes con infeccioacuten VIH por transmisioacuten vertical supone un reto
bull Riesgo de progresioacuten alto
bull Expuestos a un gran nuacutemero de ARV con fracaso terapeacuteutico frecuente
bull Mala adherencia
bull Peacuterdida de seguimiento
bull Los pacientes con mayor riesgo de progresioacuten son los que tienen mayor probabilidad de perderse tras ser transferidos a las
Unidades de adultos
bull La gestacioacuten la hospitalizacioacuten la presentacioacuten de infecciones oportunistas el ingreso en centros penitenciarios o de acogida
constituyen las causas maacutes frecuentes de reiniciar el seguimiento
bull Mientras que la negacioacuten de la enfermedad el consumo de toacutexicos los trastornos psiquiaacutetricos y la falta de soporte socio-familiar
constituyen las principales razones de abandono del seguimiento
MUJER Y VIH
iquestEXISTEN DIFERENCIAS
REALES ENTRE HOMBRES Y
MUJERES
SIhellip MUCHIacuteSIMAS
Solo desde la perspectiva de la infeccioacuten por VIH
Patogeacutenesis
Reservorio
PK-PD
Participacioacuten en ensayoscliacutenicos
Factores sociales
DIFERENCIAS DE SEXO RELACIONADAS CON EL TRATAMIENTO DEL VIH Y LA PROGRESIOacuteN DE
LA ENFERMEDAD
Female sex is associated with
Lower HIV viral load (JAIDS 20023111-19)
Higher CD4+ count (AIDS 1997111071-3)
More pronounced immune and vaccine responses (JAIDS 2011579-15)
Higher levels of immune activation (JID 2013208830-8)
More frequent ART side effects and discontinuation (J Antimicrob Chem
2007 60 724-32)
Conclusions
Gender inequalities in the response to cART are
mainly explained by the different prevalence of
socioeconomic characteristics in women compared
with men
Conclusions
It is essential to understand sex differences in
drug response as they may affect drug safety and
effectiveness
Conclusions
Women and men potentially differ in the course of
their HIV infection their response to treatment
and drug pharmacokinetics all of which are
compounded by social and behavioral factors
CASO CLIacuteNICO
bullJosefina 26 antildeos
Diagnosticada de infeccioacuten por VIH recientemente en analiacutetica rutinaria
iquestTAR a proponer
Analiacutetica
HBsAg negativo
Total anti-HBc negativo
HCV negativo
RPR (18)
PPD negative
HIV-RNA 83000 cpsmL
CD4 385 celsmm3
Examen fiacutesico sin alteraciones
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
TAR en adolescentesIntroduccioacuten
Adolescentes grupo de edad con mortalidad en ascenso Adolescentes infectados por transmisioacuten vertical (gt90)
Infeccioacuten perinatal
Infeccioacuten sintomaacutetica Pacientes ldquosupervivientesrdquo
Infeccioacuten VIH durante la adolescencia Infeccioacuten transmisioacuten sexual
Chicas relaciones heterosexuales
Chicos relaciones con hombres
Infeccioacuten transmisioacuten parenteral (drogas)
Nueva patologiacutea croacutenica
Adolescentesjoacutevenes diferencias seguacuten el tipo de transmisioacuten del VIH
bull Convivencia con el VIH desde al el nacimiento
bull Informacioacuten en pediatriacutea Mala aceptacioacuten
bull Alteraciones neurocognitivas
bull Fracaso escolar
bull TAR larga exposicioacuten Toxicidad TAR complejo
bull Comorbilidades
bull Historia de eventos sida
bull Necesidad de atencioacutensoporte psicoloacutegico
bull Consumo cannabis
bull Situacioacuten familiar compleja con frecuencia perdida de los padres
bull Dificultades para afrontar el futuro
bull Trabajo
bull Infeccioacuten VIH reciente (transmisioacuten sexual)
bull Informacioacuten en pediatriacutea o en Unidad Adultos
bull Dificultades de seguimiento
bull Reciente exposicioacuten al TAR TAR sencillo
bull Menos comorbilidades
bull No eventos sida
bull Necesidad de atencioacuten soporte psicoloacutegico
bull Tienen padres o estructura familiar no siempre
protectora
bull Dudas Planificacioacuten de futuro
Cambio fiacutesico y psicoloacutegico de la adolescencia incertidumbres
necesidad de informacioacuten en este nuevo periodo de desarrollo Miedo a la estigmatizacioacuten
Periodo de labilidad y necesidad de soporte al TAR reivindicacioacuten de sus derechos Necesidad del grupo
Infeccioacuten por transmisioacuten Vertical Infeccioacuten durante la adolescencia
Seguimiento complejo
Apoyo individualizado al cumplimiento
Informacioacuten y educacioacuten en relacioacuten a su
enfermedad
Soporte psicoloacutegico y social
Soporte de pares
Adolescentesjoacutevenes diferencias seguacuten el tipo de transmisioacuten del VIH
Paso-transferencia a la unidad de adultosGuiacuteas espantildeolas
bull La transicioacuten es un proceso individual complejo y difiacutecil en el que deben tenerse en cuenta aspectos meacutedicos psicosociales emocionales vocacionales y educacionales del paciente (AIII)
bull -La transicioacuten debe planificarse con el suficiente tiempo 2-3 antildeos no debieacutendose realizar la transicioacuten si el paciente se encuentra en una situacioacuten inestable(BIII)
bull -El equipo de pediatriacutea debe entrenar al paciente en autonomiacutea y conocimiento responsable de su infeccioacuten para que sepa asumir el cambio al sistema sanitario del adulto(AIII)
bull -El equipo de adultos debe conocer con tiempo la historia personal y meacutedica del adolescente a traveacutes de las reuniones mantenidas con el equipo pediaacutetrico asiacute como mediante un INFORMEelaborado desde pediatriacutea (CIII)
bull -La MONITORIZACION tras la transicioacuten deberiacutea realizarse al menos durante el primer antildeo para evitar peacuterdidas y fracaso de la misma (CIII)
wwwmsssigobesciudadanosenfLesionesenfTransmisiblessidapublicacionesprofSanitariosGuiaAdolescentes15Octubre2015pdf
Tratamiento ARV en adolescentes
bull Mayores problemas de adherencia
bull Cambios farmacocineacutetica Dosificacioacuten de los faacutermacos seguacuten desarrollo puberal
bull Estadio I y II Tanner dosificacioacuten pediaacutetrica
bull Estadio V dosificacioacuten ldquoadultosrdquo
bull Estadios III y IV pediaacutetricas o adultos
bull Adaptar e individualizar el tratamiento
bull Pautas de maacutes faacutecil cumplimiento
bull Preparados combinados STR
bull Tratamientos maacutes complejos bull Enfermedad avanzada acumulo de resistencias
bull Interacciones con otros faacutermacosbull Anticonceptivos Psicotropos Drogas
Resumen
bull Los adolescentes constituyen un grupo ldquominoritario y especialrdquo dentro de la poblacioacuten de pacientes con infeccioacuten VIH
bull La atencioacuten de los adolescentesadultos joacutevenes con infeccioacuten VIH por transmisioacuten vertical supone un reto
bull Riesgo de progresioacuten alto
bull Expuestos a un gran nuacutemero de ARV con fracaso terapeacuteutico frecuente
bull Mala adherencia
bull Peacuterdida de seguimiento
bull Los pacientes con mayor riesgo de progresioacuten son los que tienen mayor probabilidad de perderse tras ser transferidos a las
Unidades de adultos
bull La gestacioacuten la hospitalizacioacuten la presentacioacuten de infecciones oportunistas el ingreso en centros penitenciarios o de acogida
constituyen las causas maacutes frecuentes de reiniciar el seguimiento
bull Mientras que la negacioacuten de la enfermedad el consumo de toacutexicos los trastornos psiquiaacutetricos y la falta de soporte socio-familiar
constituyen las principales razones de abandono del seguimiento
MUJER Y VIH
iquestEXISTEN DIFERENCIAS
REALES ENTRE HOMBRES Y
MUJERES
SIhellip MUCHIacuteSIMAS
Solo desde la perspectiva de la infeccioacuten por VIH
Patogeacutenesis
Reservorio
PK-PD
Participacioacuten en ensayoscliacutenicos
Factores sociales
DIFERENCIAS DE SEXO RELACIONADAS CON EL TRATAMIENTO DEL VIH Y LA PROGRESIOacuteN DE
LA ENFERMEDAD
Female sex is associated with
Lower HIV viral load (JAIDS 20023111-19)
Higher CD4+ count (AIDS 1997111071-3)
More pronounced immune and vaccine responses (JAIDS 2011579-15)
Higher levels of immune activation (JID 2013208830-8)
More frequent ART side effects and discontinuation (J Antimicrob Chem
2007 60 724-32)
Conclusions
Gender inequalities in the response to cART are
mainly explained by the different prevalence of
socioeconomic characteristics in women compared
with men
Conclusions
It is essential to understand sex differences in
drug response as they may affect drug safety and
effectiveness
Conclusions
Women and men potentially differ in the course of
their HIV infection their response to treatment
and drug pharmacokinetics all of which are
compounded by social and behavioral factors
CASO CLIacuteNICO
bullJosefina 26 antildeos
Diagnosticada de infeccioacuten por VIH recientemente en analiacutetica rutinaria
iquestTAR a proponer
Analiacutetica
HBsAg negativo
Total anti-HBc negativo
HCV negativo
RPR (18)
PPD negative
HIV-RNA 83000 cpsmL
CD4 385 celsmm3
Examen fiacutesico sin alteraciones
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
Adolescentesjoacutevenes diferencias seguacuten el tipo de transmisioacuten del VIH
bull Convivencia con el VIH desde al el nacimiento
bull Informacioacuten en pediatriacutea Mala aceptacioacuten
bull Alteraciones neurocognitivas
bull Fracaso escolar
bull TAR larga exposicioacuten Toxicidad TAR complejo
bull Comorbilidades
bull Historia de eventos sida
bull Necesidad de atencioacutensoporte psicoloacutegico
bull Consumo cannabis
bull Situacioacuten familiar compleja con frecuencia perdida de los padres
bull Dificultades para afrontar el futuro
bull Trabajo
bull Infeccioacuten VIH reciente (transmisioacuten sexual)
bull Informacioacuten en pediatriacutea o en Unidad Adultos
bull Dificultades de seguimiento
bull Reciente exposicioacuten al TAR TAR sencillo
bull Menos comorbilidades
bull No eventos sida
bull Necesidad de atencioacuten soporte psicoloacutegico
bull Tienen padres o estructura familiar no siempre
protectora
bull Dudas Planificacioacuten de futuro
Cambio fiacutesico y psicoloacutegico de la adolescencia incertidumbres
necesidad de informacioacuten en este nuevo periodo de desarrollo Miedo a la estigmatizacioacuten
Periodo de labilidad y necesidad de soporte al TAR reivindicacioacuten de sus derechos Necesidad del grupo
Infeccioacuten por transmisioacuten Vertical Infeccioacuten durante la adolescencia
Seguimiento complejo
Apoyo individualizado al cumplimiento
Informacioacuten y educacioacuten en relacioacuten a su
enfermedad
Soporte psicoloacutegico y social
Soporte de pares
Adolescentesjoacutevenes diferencias seguacuten el tipo de transmisioacuten del VIH
Paso-transferencia a la unidad de adultosGuiacuteas espantildeolas
bull La transicioacuten es un proceso individual complejo y difiacutecil en el que deben tenerse en cuenta aspectos meacutedicos psicosociales emocionales vocacionales y educacionales del paciente (AIII)
bull -La transicioacuten debe planificarse con el suficiente tiempo 2-3 antildeos no debieacutendose realizar la transicioacuten si el paciente se encuentra en una situacioacuten inestable(BIII)
bull -El equipo de pediatriacutea debe entrenar al paciente en autonomiacutea y conocimiento responsable de su infeccioacuten para que sepa asumir el cambio al sistema sanitario del adulto(AIII)
bull -El equipo de adultos debe conocer con tiempo la historia personal y meacutedica del adolescente a traveacutes de las reuniones mantenidas con el equipo pediaacutetrico asiacute como mediante un INFORMEelaborado desde pediatriacutea (CIII)
bull -La MONITORIZACION tras la transicioacuten deberiacutea realizarse al menos durante el primer antildeo para evitar peacuterdidas y fracaso de la misma (CIII)
wwwmsssigobesciudadanosenfLesionesenfTransmisiblessidapublicacionesprofSanitariosGuiaAdolescentes15Octubre2015pdf
Tratamiento ARV en adolescentes
bull Mayores problemas de adherencia
bull Cambios farmacocineacutetica Dosificacioacuten de los faacutermacos seguacuten desarrollo puberal
bull Estadio I y II Tanner dosificacioacuten pediaacutetrica
bull Estadio V dosificacioacuten ldquoadultosrdquo
bull Estadios III y IV pediaacutetricas o adultos
bull Adaptar e individualizar el tratamiento
bull Pautas de maacutes faacutecil cumplimiento
bull Preparados combinados STR
bull Tratamientos maacutes complejos bull Enfermedad avanzada acumulo de resistencias
bull Interacciones con otros faacutermacosbull Anticonceptivos Psicotropos Drogas
Resumen
bull Los adolescentes constituyen un grupo ldquominoritario y especialrdquo dentro de la poblacioacuten de pacientes con infeccioacuten VIH
bull La atencioacuten de los adolescentesadultos joacutevenes con infeccioacuten VIH por transmisioacuten vertical supone un reto
bull Riesgo de progresioacuten alto
bull Expuestos a un gran nuacutemero de ARV con fracaso terapeacuteutico frecuente
bull Mala adherencia
bull Peacuterdida de seguimiento
bull Los pacientes con mayor riesgo de progresioacuten son los que tienen mayor probabilidad de perderse tras ser transferidos a las
Unidades de adultos
bull La gestacioacuten la hospitalizacioacuten la presentacioacuten de infecciones oportunistas el ingreso en centros penitenciarios o de acogida
constituyen las causas maacutes frecuentes de reiniciar el seguimiento
bull Mientras que la negacioacuten de la enfermedad el consumo de toacutexicos los trastornos psiquiaacutetricos y la falta de soporte socio-familiar
constituyen las principales razones de abandono del seguimiento
MUJER Y VIH
iquestEXISTEN DIFERENCIAS
REALES ENTRE HOMBRES Y
MUJERES
SIhellip MUCHIacuteSIMAS
Solo desde la perspectiva de la infeccioacuten por VIH
Patogeacutenesis
Reservorio
PK-PD
Participacioacuten en ensayoscliacutenicos
Factores sociales
DIFERENCIAS DE SEXO RELACIONADAS CON EL TRATAMIENTO DEL VIH Y LA PROGRESIOacuteN DE
LA ENFERMEDAD
Female sex is associated with
Lower HIV viral load (JAIDS 20023111-19)
Higher CD4+ count (AIDS 1997111071-3)
More pronounced immune and vaccine responses (JAIDS 2011579-15)
Higher levels of immune activation (JID 2013208830-8)
More frequent ART side effects and discontinuation (J Antimicrob Chem
2007 60 724-32)
Conclusions
Gender inequalities in the response to cART are
mainly explained by the different prevalence of
socioeconomic characteristics in women compared
with men
Conclusions
It is essential to understand sex differences in
drug response as they may affect drug safety and
effectiveness
Conclusions
Women and men potentially differ in the course of
their HIV infection their response to treatment
and drug pharmacokinetics all of which are
compounded by social and behavioral factors
CASO CLIacuteNICO
bullJosefina 26 antildeos
Diagnosticada de infeccioacuten por VIH recientemente en analiacutetica rutinaria
iquestTAR a proponer
Analiacutetica
HBsAg negativo
Total anti-HBc negativo
HCV negativo
RPR (18)
PPD negative
HIV-RNA 83000 cpsmL
CD4 385 celsmm3
Examen fiacutesico sin alteraciones
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
Seguimiento complejo
Apoyo individualizado al cumplimiento
Informacioacuten y educacioacuten en relacioacuten a su
enfermedad
Soporte psicoloacutegico y social
Soporte de pares
Adolescentesjoacutevenes diferencias seguacuten el tipo de transmisioacuten del VIH
Paso-transferencia a la unidad de adultosGuiacuteas espantildeolas
bull La transicioacuten es un proceso individual complejo y difiacutecil en el que deben tenerse en cuenta aspectos meacutedicos psicosociales emocionales vocacionales y educacionales del paciente (AIII)
bull -La transicioacuten debe planificarse con el suficiente tiempo 2-3 antildeos no debieacutendose realizar la transicioacuten si el paciente se encuentra en una situacioacuten inestable(BIII)
bull -El equipo de pediatriacutea debe entrenar al paciente en autonomiacutea y conocimiento responsable de su infeccioacuten para que sepa asumir el cambio al sistema sanitario del adulto(AIII)
bull -El equipo de adultos debe conocer con tiempo la historia personal y meacutedica del adolescente a traveacutes de las reuniones mantenidas con el equipo pediaacutetrico asiacute como mediante un INFORMEelaborado desde pediatriacutea (CIII)
bull -La MONITORIZACION tras la transicioacuten deberiacutea realizarse al menos durante el primer antildeo para evitar peacuterdidas y fracaso de la misma (CIII)
wwwmsssigobesciudadanosenfLesionesenfTransmisiblessidapublicacionesprofSanitariosGuiaAdolescentes15Octubre2015pdf
Tratamiento ARV en adolescentes
bull Mayores problemas de adherencia
bull Cambios farmacocineacutetica Dosificacioacuten de los faacutermacos seguacuten desarrollo puberal
bull Estadio I y II Tanner dosificacioacuten pediaacutetrica
bull Estadio V dosificacioacuten ldquoadultosrdquo
bull Estadios III y IV pediaacutetricas o adultos
bull Adaptar e individualizar el tratamiento
bull Pautas de maacutes faacutecil cumplimiento
bull Preparados combinados STR
bull Tratamientos maacutes complejos bull Enfermedad avanzada acumulo de resistencias
bull Interacciones con otros faacutermacosbull Anticonceptivos Psicotropos Drogas
Resumen
bull Los adolescentes constituyen un grupo ldquominoritario y especialrdquo dentro de la poblacioacuten de pacientes con infeccioacuten VIH
bull La atencioacuten de los adolescentesadultos joacutevenes con infeccioacuten VIH por transmisioacuten vertical supone un reto
bull Riesgo de progresioacuten alto
bull Expuestos a un gran nuacutemero de ARV con fracaso terapeacuteutico frecuente
bull Mala adherencia
bull Peacuterdida de seguimiento
bull Los pacientes con mayor riesgo de progresioacuten son los que tienen mayor probabilidad de perderse tras ser transferidos a las
Unidades de adultos
bull La gestacioacuten la hospitalizacioacuten la presentacioacuten de infecciones oportunistas el ingreso en centros penitenciarios o de acogida
constituyen las causas maacutes frecuentes de reiniciar el seguimiento
bull Mientras que la negacioacuten de la enfermedad el consumo de toacutexicos los trastornos psiquiaacutetricos y la falta de soporte socio-familiar
constituyen las principales razones de abandono del seguimiento
MUJER Y VIH
iquestEXISTEN DIFERENCIAS
REALES ENTRE HOMBRES Y
MUJERES
SIhellip MUCHIacuteSIMAS
Solo desde la perspectiva de la infeccioacuten por VIH
Patogeacutenesis
Reservorio
PK-PD
Participacioacuten en ensayoscliacutenicos
Factores sociales
DIFERENCIAS DE SEXO RELACIONADAS CON EL TRATAMIENTO DEL VIH Y LA PROGRESIOacuteN DE
LA ENFERMEDAD
Female sex is associated with
Lower HIV viral load (JAIDS 20023111-19)
Higher CD4+ count (AIDS 1997111071-3)
More pronounced immune and vaccine responses (JAIDS 2011579-15)
Higher levels of immune activation (JID 2013208830-8)
More frequent ART side effects and discontinuation (J Antimicrob Chem
2007 60 724-32)
Conclusions
Gender inequalities in the response to cART are
mainly explained by the different prevalence of
socioeconomic characteristics in women compared
with men
Conclusions
It is essential to understand sex differences in
drug response as they may affect drug safety and
effectiveness
Conclusions
Women and men potentially differ in the course of
their HIV infection their response to treatment
and drug pharmacokinetics all of which are
compounded by social and behavioral factors
CASO CLIacuteNICO
bullJosefina 26 antildeos
Diagnosticada de infeccioacuten por VIH recientemente en analiacutetica rutinaria
iquestTAR a proponer
Analiacutetica
HBsAg negativo
Total anti-HBc negativo
HCV negativo
RPR (18)
PPD negative
HIV-RNA 83000 cpsmL
CD4 385 celsmm3
Examen fiacutesico sin alteraciones
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
Paso-transferencia a la unidad de adultosGuiacuteas espantildeolas
bull La transicioacuten es un proceso individual complejo y difiacutecil en el que deben tenerse en cuenta aspectos meacutedicos psicosociales emocionales vocacionales y educacionales del paciente (AIII)
bull -La transicioacuten debe planificarse con el suficiente tiempo 2-3 antildeos no debieacutendose realizar la transicioacuten si el paciente se encuentra en una situacioacuten inestable(BIII)
bull -El equipo de pediatriacutea debe entrenar al paciente en autonomiacutea y conocimiento responsable de su infeccioacuten para que sepa asumir el cambio al sistema sanitario del adulto(AIII)
bull -El equipo de adultos debe conocer con tiempo la historia personal y meacutedica del adolescente a traveacutes de las reuniones mantenidas con el equipo pediaacutetrico asiacute como mediante un INFORMEelaborado desde pediatriacutea (CIII)
bull -La MONITORIZACION tras la transicioacuten deberiacutea realizarse al menos durante el primer antildeo para evitar peacuterdidas y fracaso de la misma (CIII)
wwwmsssigobesciudadanosenfLesionesenfTransmisiblessidapublicacionesprofSanitariosGuiaAdolescentes15Octubre2015pdf
Tratamiento ARV en adolescentes
bull Mayores problemas de adherencia
bull Cambios farmacocineacutetica Dosificacioacuten de los faacutermacos seguacuten desarrollo puberal
bull Estadio I y II Tanner dosificacioacuten pediaacutetrica
bull Estadio V dosificacioacuten ldquoadultosrdquo
bull Estadios III y IV pediaacutetricas o adultos
bull Adaptar e individualizar el tratamiento
bull Pautas de maacutes faacutecil cumplimiento
bull Preparados combinados STR
bull Tratamientos maacutes complejos bull Enfermedad avanzada acumulo de resistencias
bull Interacciones con otros faacutermacosbull Anticonceptivos Psicotropos Drogas
Resumen
bull Los adolescentes constituyen un grupo ldquominoritario y especialrdquo dentro de la poblacioacuten de pacientes con infeccioacuten VIH
bull La atencioacuten de los adolescentesadultos joacutevenes con infeccioacuten VIH por transmisioacuten vertical supone un reto
bull Riesgo de progresioacuten alto
bull Expuestos a un gran nuacutemero de ARV con fracaso terapeacuteutico frecuente
bull Mala adherencia
bull Peacuterdida de seguimiento
bull Los pacientes con mayor riesgo de progresioacuten son los que tienen mayor probabilidad de perderse tras ser transferidos a las
Unidades de adultos
bull La gestacioacuten la hospitalizacioacuten la presentacioacuten de infecciones oportunistas el ingreso en centros penitenciarios o de acogida
constituyen las causas maacutes frecuentes de reiniciar el seguimiento
bull Mientras que la negacioacuten de la enfermedad el consumo de toacutexicos los trastornos psiquiaacutetricos y la falta de soporte socio-familiar
constituyen las principales razones de abandono del seguimiento
MUJER Y VIH
iquestEXISTEN DIFERENCIAS
REALES ENTRE HOMBRES Y
MUJERES
SIhellip MUCHIacuteSIMAS
Solo desde la perspectiva de la infeccioacuten por VIH
Patogeacutenesis
Reservorio
PK-PD
Participacioacuten en ensayoscliacutenicos
Factores sociales
DIFERENCIAS DE SEXO RELACIONADAS CON EL TRATAMIENTO DEL VIH Y LA PROGRESIOacuteN DE
LA ENFERMEDAD
Female sex is associated with
Lower HIV viral load (JAIDS 20023111-19)
Higher CD4+ count (AIDS 1997111071-3)
More pronounced immune and vaccine responses (JAIDS 2011579-15)
Higher levels of immune activation (JID 2013208830-8)
More frequent ART side effects and discontinuation (J Antimicrob Chem
2007 60 724-32)
Conclusions
Gender inequalities in the response to cART are
mainly explained by the different prevalence of
socioeconomic characteristics in women compared
with men
Conclusions
It is essential to understand sex differences in
drug response as they may affect drug safety and
effectiveness
Conclusions
Women and men potentially differ in the course of
their HIV infection their response to treatment
and drug pharmacokinetics all of which are
compounded by social and behavioral factors
CASO CLIacuteNICO
bullJosefina 26 antildeos
Diagnosticada de infeccioacuten por VIH recientemente en analiacutetica rutinaria
iquestTAR a proponer
Analiacutetica
HBsAg negativo
Total anti-HBc negativo
HCV negativo
RPR (18)
PPD negative
HIV-RNA 83000 cpsmL
CD4 385 celsmm3
Examen fiacutesico sin alteraciones
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
Tratamiento ARV en adolescentes
bull Mayores problemas de adherencia
bull Cambios farmacocineacutetica Dosificacioacuten de los faacutermacos seguacuten desarrollo puberal
bull Estadio I y II Tanner dosificacioacuten pediaacutetrica
bull Estadio V dosificacioacuten ldquoadultosrdquo
bull Estadios III y IV pediaacutetricas o adultos
bull Adaptar e individualizar el tratamiento
bull Pautas de maacutes faacutecil cumplimiento
bull Preparados combinados STR
bull Tratamientos maacutes complejos bull Enfermedad avanzada acumulo de resistencias
bull Interacciones con otros faacutermacosbull Anticonceptivos Psicotropos Drogas
Resumen
bull Los adolescentes constituyen un grupo ldquominoritario y especialrdquo dentro de la poblacioacuten de pacientes con infeccioacuten VIH
bull La atencioacuten de los adolescentesadultos joacutevenes con infeccioacuten VIH por transmisioacuten vertical supone un reto
bull Riesgo de progresioacuten alto
bull Expuestos a un gran nuacutemero de ARV con fracaso terapeacuteutico frecuente
bull Mala adherencia
bull Peacuterdida de seguimiento
bull Los pacientes con mayor riesgo de progresioacuten son los que tienen mayor probabilidad de perderse tras ser transferidos a las
Unidades de adultos
bull La gestacioacuten la hospitalizacioacuten la presentacioacuten de infecciones oportunistas el ingreso en centros penitenciarios o de acogida
constituyen las causas maacutes frecuentes de reiniciar el seguimiento
bull Mientras que la negacioacuten de la enfermedad el consumo de toacutexicos los trastornos psiquiaacutetricos y la falta de soporte socio-familiar
constituyen las principales razones de abandono del seguimiento
MUJER Y VIH
iquestEXISTEN DIFERENCIAS
REALES ENTRE HOMBRES Y
MUJERES
SIhellip MUCHIacuteSIMAS
Solo desde la perspectiva de la infeccioacuten por VIH
Patogeacutenesis
Reservorio
PK-PD
Participacioacuten en ensayoscliacutenicos
Factores sociales
DIFERENCIAS DE SEXO RELACIONADAS CON EL TRATAMIENTO DEL VIH Y LA PROGRESIOacuteN DE
LA ENFERMEDAD
Female sex is associated with
Lower HIV viral load (JAIDS 20023111-19)
Higher CD4+ count (AIDS 1997111071-3)
More pronounced immune and vaccine responses (JAIDS 2011579-15)
Higher levels of immune activation (JID 2013208830-8)
More frequent ART side effects and discontinuation (J Antimicrob Chem
2007 60 724-32)
Conclusions
Gender inequalities in the response to cART are
mainly explained by the different prevalence of
socioeconomic characteristics in women compared
with men
Conclusions
It is essential to understand sex differences in
drug response as they may affect drug safety and
effectiveness
Conclusions
Women and men potentially differ in the course of
their HIV infection their response to treatment
and drug pharmacokinetics all of which are
compounded by social and behavioral factors
CASO CLIacuteNICO
bullJosefina 26 antildeos
Diagnosticada de infeccioacuten por VIH recientemente en analiacutetica rutinaria
iquestTAR a proponer
Analiacutetica
HBsAg negativo
Total anti-HBc negativo
HCV negativo
RPR (18)
PPD negative
HIV-RNA 83000 cpsmL
CD4 385 celsmm3
Examen fiacutesico sin alteraciones
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
Resumen
bull Los adolescentes constituyen un grupo ldquominoritario y especialrdquo dentro de la poblacioacuten de pacientes con infeccioacuten VIH
bull La atencioacuten de los adolescentesadultos joacutevenes con infeccioacuten VIH por transmisioacuten vertical supone un reto
bull Riesgo de progresioacuten alto
bull Expuestos a un gran nuacutemero de ARV con fracaso terapeacuteutico frecuente
bull Mala adherencia
bull Peacuterdida de seguimiento
bull Los pacientes con mayor riesgo de progresioacuten son los que tienen mayor probabilidad de perderse tras ser transferidos a las
Unidades de adultos
bull La gestacioacuten la hospitalizacioacuten la presentacioacuten de infecciones oportunistas el ingreso en centros penitenciarios o de acogida
constituyen las causas maacutes frecuentes de reiniciar el seguimiento
bull Mientras que la negacioacuten de la enfermedad el consumo de toacutexicos los trastornos psiquiaacutetricos y la falta de soporte socio-familiar
constituyen las principales razones de abandono del seguimiento
MUJER Y VIH
iquestEXISTEN DIFERENCIAS
REALES ENTRE HOMBRES Y
MUJERES
SIhellip MUCHIacuteSIMAS
Solo desde la perspectiva de la infeccioacuten por VIH
Patogeacutenesis
Reservorio
PK-PD
Participacioacuten en ensayoscliacutenicos
Factores sociales
DIFERENCIAS DE SEXO RELACIONADAS CON EL TRATAMIENTO DEL VIH Y LA PROGRESIOacuteN DE
LA ENFERMEDAD
Female sex is associated with
Lower HIV viral load (JAIDS 20023111-19)
Higher CD4+ count (AIDS 1997111071-3)
More pronounced immune and vaccine responses (JAIDS 2011579-15)
Higher levels of immune activation (JID 2013208830-8)
More frequent ART side effects and discontinuation (J Antimicrob Chem
2007 60 724-32)
Conclusions
Gender inequalities in the response to cART are
mainly explained by the different prevalence of
socioeconomic characteristics in women compared
with men
Conclusions
It is essential to understand sex differences in
drug response as they may affect drug safety and
effectiveness
Conclusions
Women and men potentially differ in the course of
their HIV infection their response to treatment
and drug pharmacokinetics all of which are
compounded by social and behavioral factors
CASO CLIacuteNICO
bullJosefina 26 antildeos
Diagnosticada de infeccioacuten por VIH recientemente en analiacutetica rutinaria
iquestTAR a proponer
Analiacutetica
HBsAg negativo
Total anti-HBc negativo
HCV negativo
RPR (18)
PPD negative
HIV-RNA 83000 cpsmL
CD4 385 celsmm3
Examen fiacutesico sin alteraciones
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
MUJER Y VIH
iquestEXISTEN DIFERENCIAS
REALES ENTRE HOMBRES Y
MUJERES
SIhellip MUCHIacuteSIMAS
Solo desde la perspectiva de la infeccioacuten por VIH
Patogeacutenesis
Reservorio
PK-PD
Participacioacuten en ensayoscliacutenicos
Factores sociales
DIFERENCIAS DE SEXO RELACIONADAS CON EL TRATAMIENTO DEL VIH Y LA PROGRESIOacuteN DE
LA ENFERMEDAD
Female sex is associated with
Lower HIV viral load (JAIDS 20023111-19)
Higher CD4+ count (AIDS 1997111071-3)
More pronounced immune and vaccine responses (JAIDS 2011579-15)
Higher levels of immune activation (JID 2013208830-8)
More frequent ART side effects and discontinuation (J Antimicrob Chem
2007 60 724-32)
Conclusions
Gender inequalities in the response to cART are
mainly explained by the different prevalence of
socioeconomic characteristics in women compared
with men
Conclusions
It is essential to understand sex differences in
drug response as they may affect drug safety and
effectiveness
Conclusions
Women and men potentially differ in the course of
their HIV infection their response to treatment
and drug pharmacokinetics all of which are
compounded by social and behavioral factors
CASO CLIacuteNICO
bullJosefina 26 antildeos
Diagnosticada de infeccioacuten por VIH recientemente en analiacutetica rutinaria
iquestTAR a proponer
Analiacutetica
HBsAg negativo
Total anti-HBc negativo
HCV negativo
RPR (18)
PPD negative
HIV-RNA 83000 cpsmL
CD4 385 celsmm3
Examen fiacutesico sin alteraciones
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
iquestEXISTEN DIFERENCIAS
REALES ENTRE HOMBRES Y
MUJERES
SIhellip MUCHIacuteSIMAS
Solo desde la perspectiva de la infeccioacuten por VIH
Patogeacutenesis
Reservorio
PK-PD
Participacioacuten en ensayoscliacutenicos
Factores sociales
DIFERENCIAS DE SEXO RELACIONADAS CON EL TRATAMIENTO DEL VIH Y LA PROGRESIOacuteN DE
LA ENFERMEDAD
Female sex is associated with
Lower HIV viral load (JAIDS 20023111-19)
Higher CD4+ count (AIDS 1997111071-3)
More pronounced immune and vaccine responses (JAIDS 2011579-15)
Higher levels of immune activation (JID 2013208830-8)
More frequent ART side effects and discontinuation (J Antimicrob Chem
2007 60 724-32)
Conclusions
Gender inequalities in the response to cART are
mainly explained by the different prevalence of
socioeconomic characteristics in women compared
with men
Conclusions
It is essential to understand sex differences in
drug response as they may affect drug safety and
effectiveness
Conclusions
Women and men potentially differ in the course of
their HIV infection their response to treatment
and drug pharmacokinetics all of which are
compounded by social and behavioral factors
CASO CLIacuteNICO
bullJosefina 26 antildeos
Diagnosticada de infeccioacuten por VIH recientemente en analiacutetica rutinaria
iquestTAR a proponer
Analiacutetica
HBsAg negativo
Total anti-HBc negativo
HCV negativo
RPR (18)
PPD negative
HIV-RNA 83000 cpsmL
CD4 385 celsmm3
Examen fiacutesico sin alteraciones
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
SIhellip MUCHIacuteSIMAS
Solo desde la perspectiva de la infeccioacuten por VIH
Patogeacutenesis
Reservorio
PK-PD
Participacioacuten en ensayoscliacutenicos
Factores sociales
DIFERENCIAS DE SEXO RELACIONADAS CON EL TRATAMIENTO DEL VIH Y LA PROGRESIOacuteN DE
LA ENFERMEDAD
Female sex is associated with
Lower HIV viral load (JAIDS 20023111-19)
Higher CD4+ count (AIDS 1997111071-3)
More pronounced immune and vaccine responses (JAIDS 2011579-15)
Higher levels of immune activation (JID 2013208830-8)
More frequent ART side effects and discontinuation (J Antimicrob Chem
2007 60 724-32)
Conclusions
Gender inequalities in the response to cART are
mainly explained by the different prevalence of
socioeconomic characteristics in women compared
with men
Conclusions
It is essential to understand sex differences in
drug response as they may affect drug safety and
effectiveness
Conclusions
Women and men potentially differ in the course of
their HIV infection their response to treatment
and drug pharmacokinetics all of which are
compounded by social and behavioral factors
CASO CLIacuteNICO
bullJosefina 26 antildeos
Diagnosticada de infeccioacuten por VIH recientemente en analiacutetica rutinaria
iquestTAR a proponer
Analiacutetica
HBsAg negativo
Total anti-HBc negativo
HCV negativo
RPR (18)
PPD negative
HIV-RNA 83000 cpsmL
CD4 385 celsmm3
Examen fiacutesico sin alteraciones
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
DIFERENCIAS DE SEXO RELACIONADAS CON EL TRATAMIENTO DEL VIH Y LA PROGRESIOacuteN DE
LA ENFERMEDAD
Female sex is associated with
Lower HIV viral load (JAIDS 20023111-19)
Higher CD4+ count (AIDS 1997111071-3)
More pronounced immune and vaccine responses (JAIDS 2011579-15)
Higher levels of immune activation (JID 2013208830-8)
More frequent ART side effects and discontinuation (J Antimicrob Chem
2007 60 724-32)
Conclusions
Gender inequalities in the response to cART are
mainly explained by the different prevalence of
socioeconomic characteristics in women compared
with men
Conclusions
It is essential to understand sex differences in
drug response as they may affect drug safety and
effectiveness
Conclusions
Women and men potentially differ in the course of
their HIV infection their response to treatment
and drug pharmacokinetics all of which are
compounded by social and behavioral factors
CASO CLIacuteNICO
bullJosefina 26 antildeos
Diagnosticada de infeccioacuten por VIH recientemente en analiacutetica rutinaria
iquestTAR a proponer
Analiacutetica
HBsAg negativo
Total anti-HBc negativo
HCV negativo
RPR (18)
PPD negative
HIV-RNA 83000 cpsmL
CD4 385 celsmm3
Examen fiacutesico sin alteraciones
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
Conclusions
Gender inequalities in the response to cART are
mainly explained by the different prevalence of
socioeconomic characteristics in women compared
with men
Conclusions
It is essential to understand sex differences in
drug response as they may affect drug safety and
effectiveness
Conclusions
Women and men potentially differ in the course of
their HIV infection their response to treatment
and drug pharmacokinetics all of which are
compounded by social and behavioral factors
CASO CLIacuteNICO
bullJosefina 26 antildeos
Diagnosticada de infeccioacuten por VIH recientemente en analiacutetica rutinaria
iquestTAR a proponer
Analiacutetica
HBsAg negativo
Total anti-HBc negativo
HCV negativo
RPR (18)
PPD negative
HIV-RNA 83000 cpsmL
CD4 385 celsmm3
Examen fiacutesico sin alteraciones
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
CASO CLIacuteNICO
bullJosefina 26 antildeos
Diagnosticada de infeccioacuten por VIH recientemente en analiacutetica rutinaria
iquestTAR a proponer
Analiacutetica
HBsAg negativo
Total anti-HBc negativo
HCV negativo
RPR (18)
PPD negative
HIV-RNA 83000 cpsmL
CD4 385 celsmm3
Examen fiacutesico sin alteraciones
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
009008003004
TSEPAMO NTD PREVALENCE BY ARV EXPOSURE
bull As of March 2019 rate of NTDs with DTG at conception lower than initially signaled[12]
bull No significant difference in major external structural malformations with DTG vs non-DTG ART[12]
bull WHO released updated recommendations reconfirming use of DTG-based ART as preferred first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV
Negative
(n = 89372)
DTG
(n = 1683)
Non-DTG
(n = 14792)
EFV
(n = 7959)
NTDs per exposures nN 51683 1514792 37959 13840 7089372
Prevalence difference (95 CI) Reference020
(001-059)
026
(007-066)
027
(006-067)
022
(005-062)
NTDs per exposures since May 2018
nN11275 13492 02172 11028 923315
1 Zash IAS 2019 Abstr MOAX0105LB 2 Zash NEJM 2019[Epub] 3 WHO ARV Policy Update July 2019
Pre-May 2018Current analysis
DTG Any Non-DTG ART
EFV HIV Negative
Pregnancy
NTD
s
(9
5
CI)
DTG
Conception
030
010 005 000
05
1
0
094
012
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
UPDATED WHO GUIDANCE ON DTG USE IN TREATMENT-NAIVE WOMEN OF
CHILDBEARING POTENTIAL
WHO Guidancebull DTG can be prescribed for adult women and adolescent girls of childbearing age or potential who wish to
become pregnant or who are not otherwise using or accessing consistent and effective contraception if they have
been fully informed of the potential increase in the risk of neural tube defects (at conception and until
the end of the first trimester)
WHO ARV Policy Update July 2019
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
bull Todas las gestantes en TAR para evitarTMFbull Diferentes opciones terapeuacuteticas seguacuten la
situacioacuten en el momento de la gestacioacuten
ndashPautas preferentes en naiumlve (mayor experienciay seguridad)bullTDFFTC oABC3TC +
bullRAL (400 mg BID) DRVr o ATVr
ndashPautas desaconsejadas DTG 1T DRVc TAF
TAR EN MUJER GESTANTE O CON DESEO GESTACIONAL
GESIDA
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
TAR en pacientes vulnerables
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
The impact of unstable housing on HIV treatment outcomes in people living with HIVAIDS in an urban setting of Southern
EuropePE116Authors Knobel H1 Guelar A1 Letang E12 Aciacuten P3 Fernaacutendez -Sala X3 Mariacuten J4 Lerma E1 Arrieta I1 Gonzaacutelez A1
1Infectious Diseases Dept Hospital del Mar Barcelona Spain 2 ISGlobal Barcelona Spain 3Pharmacy Dept Hospital del Mar Barcelona Spain 4 Autonommous University of Barcelona
Background People living with HIV (PLHIV) with unstable housing (UH) face several
barriers hindering access to care adherence to antiretroviral therapy (ART) retention in
care and treatment success Despite being on the rise this phenomenon has been scarcely
characterized in Southern Europe
Methods A prospective cohort study was conducted with patients who started or resumed
(more than one year without treatment) antiretroviral treatment (ART) between January
2012 and June 2018 in a university hospital in Barcelona Spain
The following data was collected demographics baseline viral load CD4 cell count alcohol
use current substance use language and cultural barrier unstable housing concerns and
negative beliefs about treatment loss of previous appointments psychiatric disorder
(depression psychosis)
Adherence was evaluated every 2 months by pharmacy refills and by self-reports A patient
with lt90 of prescribed dose and or ART interruption for more than one week was
considered non-adherent
Treatment failure (TF) was considered when patient not achieved and maintained viral load
lt500 copiesml or was lost of follow-up or death Adequate CD4+ T-cell count
(CD4gt350 cellsml) at the last follow-up
The statistical analysis included descriptive statistics chi-square test and Cox regression
analysis
Results We included 570 patients contributing 1014 person-years of follow-up with a
median time of 2135 months Among them 115 (2017) had UH The baseline
characteristics of people with UH included are shown in the table
The table shows non-adherence virologic failure TF and adequate CD4 cell count in
patients with and without unstable housing
OutcomesNon-Unstable housing
N 455
Unstable housing
N 115
P
Non-adherence N () 94 (207) 97 (757) 0000
Viral load lt 50 copiesml N () 409 (899) 73 (635) 0000
Treatment failure N () 83 (182) 56 (487) 0000
Adequate CD4+ cell response N() 359 (79) 61 (53) 0001
Conclusions
bull The proportion of unstable housing was common in this Southern European
urban cohort of People living with HIV
bull PLHIV with UH had a high comorbidity burden and suboptimal ART outcomes
including poorer adherence retention in care adequate immune recovery and
treatment success
bull Specific interventions are needed for this neglected population
UH independently predicted TF (HR 187 122-285) after adjusting for HIV-RNA (HR 127 per
log10 increase 95 CI 100-161) current recreational drug use (HR 209 95 CI 140-312)
and patient prejudgment (HR 216 95 CI 123-380)
Baseline characteristicsAge Mean (SD) 4181 (884) Alcoholism N () 34 (296)
HIV-RNA log10ml Median (IQR) 476 (423-
512)
Drug User N () 74 (643)
CD4 cell count Cellsml Median
(IQR)
257 (117-446) Psychiatric disorder N () 42 (365)
Male N () 89 (774) Idiomaticcultural barrier N( ) 28 (243)
HIV acquisition IDU N() 77 (67) Patient prejudgment N () 6 (52)
STR N () 55 (478) Previous appointments failure N 53 (461)
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
HIV IN THE NEW MILLENNIUM A SOCIAL MEDICAL NEXUS
Mental
Illness
Poverty Drugs
Infectious
Diseases
HIV
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
LA ATENCIOacuteN CULTURALMENTE COMPETENTE PUEDE MEJORAR LA
COMUNICACIOacuteN Y LA CONFIANZA
bull Adaptacioacuten cultural
bull Servicios de inteacuterprete y mediadores culturales
bull Reclutar retener al personal representante de la comunidad de pacientes
bull Proporcionar folletos culturalmente apropiados actividades en idiomas
relevantes
bull Incluir a la familia y a la comunidad en la atencioacuten
bull Preguntar a los pacientes queacute necesitan y aborden esas necesidades
bull Hacer de la cliacutenica un lugar deseable para ir
Stone V et al HIVAIDS in US Communities of Color Springer 2009
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
Puede haber una serie de razones por las cuales alguien
termina sin hogar incluida la peacuterdida repentina de
trabajo o el colapso familiar el abuso grave de
sustancias o los problemas de salud mental Pero la
mayoriacutea de las poliacuteticas de personas sin hogar funcionan
bajo la premisa de que la persona sin hogar tiene que
resolver esos problemas primero antes de poder obtener
un alojamiento permanente
Finlandia hace lo contrario primero les da un hogar
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
EVOLUCIOacuteN DE LA INFECCIOacuteN POR VIH DE FATAL A CROacuteNICA
bull Prospective observational study of persons with HIV in the Cohort of the Spanish AIDS Research Network (CoRIS) from 2004 to 2014 (N = 9569)
Increasing Proportion of Older HIV+ Persons in Spain
Alejos AIDS 2016 Abstr WEPDB0105
Age Yrs
Pro
po
rtio
n o
f To
tal P
ers
on
-Yrs
(
)
20040
20
40
60
80
100
2005 2006 2007 2008 2009 2010 2011 2012 20142013
gt 64 60-6455-5950-54lt 50
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
ENVEJECIMIENTO POLIFARMACIA E INTERACCIONES EN PACIENTES CON VIH
En pacientesVIH gt 50 antildeos Prescripcioacuten
potencialmente inapropiada en 54 y 63 de
pacientes empleando los criterios STOPP y
Beers respectivamente
McNicholl IR1 Gandhi M2 Hare CB3 Greene M4 Pierluissi E5 Pharmacotherapy 2017 Oct 10
En 265 pacientes gt 65 antildeos 65 de
interacciones potenciales 66 interacciones
severas
Bastida C1 Grau A2 Maacuterquez M3 Tuset M4 De Lazzari E5 Martiacutenez E6 Gatell JM7 Farm Hosp
2017 Sep 141(5)618-624
Cohorte Francia En pacientes gt 50 antildeos es muy
frecuente la comorbilidad (62) y la
comedicacioacuten (71)
Cuzin l et al HIV Med 2017 Jul18(6)395-401
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
HIV drug
Co-med
Perpetrator
Victim
AEs AEs
Loss of efficacy
Loss of efficacy
LAS TERAPIAS PARA LAS COMORBILIDADES AUMENTAN EL RIESGO DE IF
Graphic courtesy of Dr David Back Hughes CMAJ 201518736
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
Back D CROI 2019 Abstract 120Perpetrator Victim
Top Global Co-medication Searches 2018
PPI proton pump inhibitor
helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip50helliphelliphelliphelliphelliphelliphellip100helliphelliphelliphelliphelliphelliphelliphellip200helliphellip1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
-
10000
20000
30000
40000
50000
60000
No o
f Q
ueri
es
Statins
PPIsH2 blockers
Antidiabetics
Analgesics
Antihypertensives
Anti-infectives
Psychotropic drugs
Erectile dysfunction agents
Mineral supplements
Corticosteroids
AntiplateletsAnticoagulants
HIV DDIs searched 2018
Website
308M76
App
955K
24
Top 25 Co-medications Generating the Most DDI Queries in wwwhiv-druginteractionsorg (MixPanel Analytics)
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
MAJOR CO-MORBIDITIES IN THE STUDYPOPULATION (N10897 )
33
48
20
47
59
28
Cardiovascular disease Renal impairment Fracture
2010
2014
Events in 2010 (n) 356 520 215
Events in 2014 (n) 512 648 306
p lt0001
p lt0001
p lt0001
Knobel H et al Enferm Infecc Microbiol Clin 2019
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
Cardiovascular disease
Age distribution in the rate of co-morbidities and
their risk factors in the two periods 2010
2014
0505
1919
4244
74
95
134
149
Renal impairment
18
08
32 32
58 57
83
97
185
197
Fracture
07 07
1822 23
30 29
36 37
45
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
EACS Guidelines October 2018 Slide credit clinicaloptionscom
EL PERFIL DE TOXICIDAD DE CIERTOS ARV PUEDE AFECTAR NEGATIVAMENTE LAS
COMORBILIDADES
Class Agent Select AEs
NRTIABC Ischemic heart disease
TDF darr BMD osteomalacia uarr fracture risk darr eGFR Fanconi syndrome
NNRTI EFV Depression sleep disturbance headache suicidal ideation
PI
ATV darr eGFR nephrolithiasis
DRV Ischemic heart disease nephrolithiasis
LPV Ischemic heart disease darr eGFR
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
TOXICIDAD RENAL CON TENOFOVIR FACTORES DE RIESGO PATOGEacuteNESIS
bull Most tenofovir eliminated through glomerular filtration with 20 to 30 excreted though tubular secretion[1]
RTV RTV
uarr Tenofoviruarr Tenofovir
Results in kidney injury progressive
darr eGFR
OAT3
MRP2
MRP4
Blood Urine
1 Venter South Afr J HIV Med 201819817 2 Baxi AIDS 20142859 3 Yombi AIDS 201428621
Renal Tubular Cell[3]
OAT1uarr Age darr BMI or
Concomitant RTV[2]
Estimated Fold-Effect[2] TDF
AUCP Value
Concomitant RTV use uarr 133 0020
Per decade of age uarr 121 0007
Black vs nonblack uarr 104 68
Per 10 increase in BMI darr 096 019
eGFR lt 70 mLmin173 m2 uarr 131 094
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
Medicine (2016) 9541(e5146)
Metaanaacutelisis TAF Vs TDF- Mejoriacutea en Hueso lt descenso de DMO gt 3
- Menos efectos adversos renales
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
LAS PVVIH TIENEN FACTORES DE RIESGO CV ADICIONALES NO CONTABILIZADOS CON
LAS ESCALAS TRADICIONALES
T-Cell Activation Monocyte Activation
uarr High-Risk (Noncalcified) Plaque
Residual Viral Replication Microbial Translocation Immune Deficiency
uarr Arterial Wall Inflammation
Coronary computedtomography angiography
18F-FDG-PET
Slide courtesy of Dr Steven Grinspoon Hsue Can J Cardiol 201935238
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
EL TRATAMIENTO DE LA COMORBILIDAD PUEDE SER MAacuteS EFECTIVO QUE EL CAMBIO DEL TAR
bull Open-label randomized study of virologically-suppressed adults receiving RTV-boosted PI therapy with fasting TC ge 55 mmolL and elevated CV risk (Framingham score ge 8 at 10 yrs or diabetes or first-degree relative with premature CAD)
Lee HIV Med 201617605
Switch RTV-boosted PIRosuvastatin (10 mgday)
Me
an Δ
Fro
m B
L at
Wk
12
TriglyceridesLDLTC TCHDLHDL VLDL-40
-30
-20
-10
0
10
-87 -214 +03 +24 -10 -299 -370 -150 -76 -227 -341 -98
P = 003 P lt 001 P = 006 P = 002 P = 005P = 574
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
CONCLUSIONES
bull Las comorbilidades son cada vez maacutes frecuentes en el envejecimiento de las PVVIH
bull Necesidad de prevencioacuten y manejo
bull Considerar las comorbilidades como criterio durante la seleccioacuten de TAR de primera liacutenea y en el cambio de TAR
bull Considerar las IF como un criterio para cambiar el TAR eleccioacuten de faacutermacos adaptados a la comorbilidad preferencia de TAR con pocas interacciones
bull A veces tratar una comorbilidad es maacutes efectivo que sustituir un faacutermaco antirretroviral
