Berta Pernas1, Andrés Tabernilla1, Marta Grandal1, Angelina Cañizares2, Sofía Ortún1, Ángeles Castro-Iglesias1, Álvaro Mena1, Iria Rodríguez-Osorio1, Héctor Meijide1, Eva Poveda1.

1Grupo de Virología Clínica. Instituto de Investigación Biomédica de A Coruña (INIBIC)-Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade deA Coruña (UDC). A Coruña, España.2Servicio de Microbiología. Instituto de Investigación Biomédica de A Coruña (INIBIC)-Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS. A Coruña,España.

Prevalence of Transmitted Drug ResistanceMutations among Naive HIV-infected patients

(2014-2016) in Northwest Spain

BACKGROUND• Antiretroviral Treatment (ART) has dramatically changed the natural

history of HIV infection, reducing viral burden and HIV-relatedmorbidity and mortality.1

• The transmission of drug resistance among adults recently infected isa consequence of the widespread use of antiviral agents.2,3

• Transmitted Drug Resistance (TDR) in naïve HIV-infected patients hasbeen associated with suboptimal response to antiretroviral drugs.4

• Active surveillance of TDR provides important information about thefactors involved in the transmission of resistant HIV strains and in theselection of ART components.5,6

1Palella et al. N Engl J Med 1998. 2Johnson et al. Top HIV Med 2008. 3Yebra et al. Med Clin (Barc.) 2010. 4Monge et al. PLoS One 2014. 5Hecht et al. J Infect Dis 2006.6Ambrosioni et al. PLoS One 2015.

Integrase inhibitors (INI)-based regimens are recommended as first line therapies

ABC/3TC/DTGTFV/FTC+DTGTFV/FTC+RALTAF/FTC/EVG/COBI

ABC/3TC/TDGTAF/FTC or TDF/FTC+DTGTAF/FTC/EVG/c or TDF/FTC/EVG/cTAF/FTC or TDF/TFC + RAL

ABC/3TC/DTGTAF/FTC or TDF/FTC+DTGTAF/FTC/EVG/c or TDF/FTC/EVG/cTAF/FTC or TDF/TFC + RAL

TAF/FTC or TDF/FTC + DRV/c or DRV/r TAF/FTC or TDF/FTC + DRV/r

TAF/FTC/RPV or TDF/FTC/RPV

Drug-Resistance Testing

• Se recomienda realizar un estudio genotípico deresistencias del VIH-1 a la transcriptasa inversa yproteasa en todos los pacientes antes de iniciar el TAR(A-II).

• Se debe conocer el resultado del estudio genotípico si seva a iniciar TAR con ITINN (A-II).

• Solo se recomienda estudiar resistencias basales en laintegrasa si existe alta sospecha de transmisión deresistencias a esta familia (C-III).

• Genotypic resistance testing is recommended prior toinitiation of ART, ideally at the time of HIV diagnosis;otherwise before initiation of ART.

• HIV drug-resistance testing is recommended for persons with HIVinfection at entry into care to guide selection of the initiation ofART regimen (AII). If therapy is deferred, repeat testing may beconsidered at the time of ART initiation (CIII).

• In special circumstances (e.g. in patients with acute or recent HIVinfection and in pregnant HIV-infected women), ART initiationshould not be delayed while awaiting resistance testing results;the regimen can be modified once results are reported (AIII).

• Standard genotypic drug-resistance testing in ARV-naive personsinvolves testing for mutations in the reverse transcriptase (RT)and protease (PR) genes. If transmistted integrase strand transferinhibitor (INSTI) resistance is a concern, providers should ensurethat genotypic resistance testing also includes INSTI genotypetesting.

OBJECTIVE

The goal of the study was to evaluate the prevalence of TDR to reversetranscriptase, protease and integrase inhibitors among naïve HIV-infected patients in the medical area of A Coruña.

MATERIAL and METHODS • All naïve HIV-infected patients in clinical follow-up during 2014-2016 were

identified.• Epidemiological and immune-virological characteristics were recorded.• HIV reverse transcriptase, protease and integrase regions were amplified

and sequenced from plasma samples and FASTA format sequences wereobtained.

• The presence of TDR was evaluated following the last HIV drug resistanceupdate of WHO and International AIDS Society (2017).

• HIV-1 subtypes were assigned using the Stanford University DrugResistance Database algorithm.

n = 92

Gender (male) 84 (91.3)

Age (years) 37 ± 11

Spanish nationality 76 (86.4)

Route of TransmissionMSMHeterosexualIDU

57 (66.3)24 (27.9)

5 (5.8)

AIDS-defining Disease 3 (3.3)

Late Diagnosis (CD4 ≤ 350 cells/µL and/or AIDS-defining disease) 24 (27.9)

Mean CD4+ cell count at diagnosis time (cells/µL) 503 ± 287

Mean Viral Load (HIV-RNA) at diagnosis time (log copies/mL) 4.75 ± 0.74

Viral Hepatitis Co-InfectionHBsAg positiveHCV antibodies

2 (2.2)8 (8.7)

Baseline Characteristics of the Study Population

Data are presented as n (%)

Major TDR mutations for INI were not identified

7.6%

3.3%

5.4%

1.1%

0%

2.2%

0

1

2

3

4

5

6

7

8

9

10

Total NRTI NNRTI PI INI T97A*

Prev

alen

ce o

f TDR

(%)

* The accessory INI T97A mutation was recognized in naive HIV-infected patients diagnosed before 2014.

No significant differences in TDR prevalence wereobserved between subtypes B and F

64.1%

23.9%

3.3%2.2%

2.2% 2.2% 1.1%1.1%

B

F

A

G

CRF01_AE

CRF02_AG

C

K

5.1%

3.4%1.7% 1.7%

13.6%

4.5%

13.6%

0%0

2

4

6

8

10

12

14

16

TDR NRTI NNRTI PIPr

eval

ence

of T

DR (%

)

Subtype B Subtype F

p = 0.337

p = 0.999

p = 0.059

p = 0.999

All TDR mutations for RT and Protease were identified in HIV-infectedpatients diagnosed during 2014-2016

TDRReverse Transcriptase

NRTI NNRTI

Major

M41L 2 (2.2) K103N 2 (2.2)

T69D 1 (1.1) E138A 1 (1.1)

T219R 1 (1.1) Y181V 1 (1.1)

G190A 1 (1.1)

MinorV106I 19 (20.7)

V179D 1 (1.1)

Data are presented as n (%)

Subtype F

Protease polymorphisms werecommon (57.6%)

TDR at HIV Protease

Major Minor and/or Polymorphisms

D30N 1 (1.1) L10I 9 (9.8)

N88D 1 (1.1) L10V 20 (21.7)

K20R 3 (3.3)

K20M 1 (1.1)

K20I 4 (4.3)

M36I 41 (44.6)

M36L 2 (2.2)

M36V 1 (1.1)

L63P 29 (31.5)

A71T 9 (9.8)

A71V 4 (4.3)

V77I 23 (25)

V82I 3 (3.3)

L89M 33 (35.9)

I93L 24 (26.1)

35.6%

1.7%

18.6%

100%

86.4%90.9%

0

10

20

30

40

50

60

70

80

90

100

Polymorphism L10V M36I

HIV-

infe

cted

patie

ntsw

ithTD

R (%

)

Protease Polymorphisms

Subtype B Subtype F

p < 0.001

Data are presented as n (%)

CONCLUSIONS• TDR prevalence in naïve HIV-infected patients was 3.3%, 5.4% and

1.1% for NRTI, NNRTI and PI, respectively, similar to those previouslyreported.

• Although no major TDR for INI were identified, mutation T97A wasidentified in 2.2% of patients.

• These results suggest that testing resistance to INI is not necessaryyet before initiating treatment among HIV-infected naïve patients.

ACKNOWLEDGEMENTS

Grupo de Virología Clínica