Antiretroviral Drug Resistance in HIV Sequences From People Who Inject Drugs and Men Who Have Sex With Men Across 21 Cities in India

Abstract

Background: Drug resistance testing is limited in public-sector human immunodeficiency virus (HIV) care in India, and there are few systematic samplings for prevalent drug resistance mutations (DRMs), particularly among men who have sex with men (MSM) and people who inject drugs (PWID).

Methods: We conducted genotypic resistance testing on 915 HIV sequences sampled from viremic self-reported antiretroviral therapy (ART) experienced and naive PWID and MSM recruited from 21 cities across India in 2016-2017. We analyzed factors associated with resistance using logistic regression and evaluated evidence for transmitted resistance using phylogenetic analyses.

Results: Of the 915 participants sequenced, median age was 31, 436 were MSM, and 191 were ART experienced. Overall, 62.8% of ART-experienced participants and 14.4% of ART-naive participants were found to have low-level resistance or higher to 1 or more classes of drugs. Prevalence of tenofovir disoproxil fumarate resistance was 25.7% in ART-experienced participants and 1.11% in ART-naive participants. The highest proportion of drug resistance was seen across nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, and resistance was significantly more common among MSM participants than PWID. Phylogenetic analyses revealed that 54.6% of ART-naive participants with resistance who clustered had shared DRMs, suggesting transmitted resistance may have occurred.

Conclusions: Patients experiencing virologic failure on first-line therapy switched blindly to tenofovir/lamivudine/dolutegravir may effectively be receiving dolutegravir monotherapy due to resistance to tenofovir and lamivudine. While dolutegravir is expected to have full activity in the majority of patients in India, follow-up is needed to understand how resistance may affect long-term outcomes.

Keywords: DRM; India; LMIC; MSM; PWID; phylogenetics.

Figure 1.

Prevalence of drug resistance mutations among self-reported antiretroviral therapy (ART)–experienced people who inject drugs (PWID) (n = 48) and men who have sex with men (MSM) (n = 143) (A) and self-reported ART-naive PWID (n = 431) and MSM (n = 293) (B) across 21 cities in India, 2016–2017. Only major protease inhibitor mutations and mutations present in >2 samples are shown.

Figure 2.

Human immunodeficiency virus antiretroviral (ARV) drug resistance among 120 ART-experienced (A) and 104 ART-naive (B) men who have sex with men and people who inject drugs with low-level drug resistance or higher across 21 cities in India, 2016–2017. Each row represents an individual participant sample. Columns represent ARV drugs, and colors denote drug resistance levels. The figure is oriented from top to bottom, depicting descending overall resistance. Abbreviations: /r, ritonavir; 3TC, lamivudine; ABC, abacavir; ATV, atazanavir; d4T, stavudine; DDI, didanosine; DOR, doravirine; DRV, darunavir; EFV, efavirenz; ETR, etravirine; FPV, fosamprenavir; FTC, emtricitabine; IDV, indinavir; LPV, lopinavir; NFV, nelfinavir; NNRTI, nonnucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; NVP, nevirapine; PI, protease inhibitor; RPV, rilpivirine; SQV, saquinavir; TDF, tenofovir disoproxil fumarate; TPV, tipranavir; ZDV, zidovudine.

Figure 3.

Prevalence and level of antiretroviral drug resistance among 915 representative human immunodeficiency virus (HIV) type 1 sequences from men who have sex with men and people who inject drugs sampled in 2016–2017 across 21 cities in India (A), as well as among 191 participants aware of their HIV status with self-report of ever taking antiretroviral therapy (ART) (B), among 210 participants aware of their HIV status and no self-reported history of ever taking ART (C) and among 514 participants unaware of their HIV status (and ART-naive) (D). Abbreviations: /r, ritonavir; 3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; ATV, atazanavir; d4T, stavudine; DDI, didanosine; DOR, doravirine; DRV, darunavir; EFV, efavirenz; ETR, etravirine; FPV, fosamprenavir; FTC, emtricitabine; HIV, human immunodeficiency virus; IDV, indinavir; LPV, lopinavir; NFV, nelfinavir; NNRTI, nonnucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; NVP, nevirapine; PI, protease inhibitor; RPV, rilpivirine; SQV, saquinavir; TDF, tenofovir disoproxil fumarate; TPV, tipranavir; ZDV, zidovudine.

Figure 4.

Maximum likelihood phylogenetic tree of 915 human immunodeficiency virus type 1 partial pol sequences isolated from men who have sex with men and people who inject drugs across 21 cities in India inferred under a general time-reversible + Γ4 + I evolutionary model. Branches with like-colored tip shapes denote transmission clusters at a 1.5% genetic distance threshold. Branches without tip shapes denote sequences that did not cluster.