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BackgroundPersons who inject drugs (PWID) have high HIV incidence and prevalence, and may have limited access to antiretroviral therapy (ART) in some settings. We evaluated HIV drug resistance in PWID in a randomized clinical trial (HPTN 074). The study intervention included ART at any CD4 cell count with enhanced support for ART and substance use treatment.MethodsHPTN 074 enrolled HIV-infected PWID (index participants) with viral loads ≥1,000 copies/mL and their HIV-uninfected injection-network partners in Indonesia, Ukraine, and Vietnam; the study limited enrollment of people who reported being on ART. HIV drug resistance testing and antiretroviral (ARV) drug testing were performed using samples collected from index participants at study enrollment.ResultsFifty-four (12.0%) of 449 participants had HIV drug resistance; 29 (53.7%) of the 54 participants had multi-class resistance. Prevalence of resistance varied by study site and was associated with self-report of prior or current ART, detection of ARV drugs, and a history of incarceration. Resistance was detected in 10 (5.6%) of 177 newly diagnosed participants. Participants with resistance at enrollment were less likely to be virally suppressed after 52 weeks of follow-up, independent of study arm.ConclusionsIn HPTN 074, many of the enrolled index participants had HIV drug resistance and more than half of those had multi-class resistance. Some newly-diagnosed participants had resistance, suggesting that they may have been infected with drug-resistant HIV strains. Behavioral and geographic factors were associated with baseline resistance. Baseline resistance was associated with reduced viral suppression during study follow-up. These findings indicate the need for enhanced HIV care in this high-risk population to achieve sustained viral suppression on ART.

Background The HIV Prevention Trials Network (HPTN) 075 study evaluated the feasibility of enrolling and retaining men who have sex with men (MSM) and transgender women (TWG) from Kenya, Malawi, and South Africa. Twenty-one participants acquired HIV during study follow-up (seroconverters). We analyzed HIV subtype diversity, drug resistance, transmission dynamics, and HIV superinfection among MSM and TGW enrolled in HPTN 075. Methods HIV genotyping and drug resistance testing was performed for HIV-positive participants who had viral loads >400 copies/mL at screening (prevalent cases, N=124) and seroconverters (N=21). HIV pol clusters were identified using Cluster Picker. Superinfection was assessed by longitudinal analysis of env and pol sequences generated by next-generation sequencing. Results HIV genotyping was successful for 123/124 prevalent cases and all 21 seroconverters. The major HIV subtypes were A1 (Kenya) and C (Malawi and South Africa). Major drug resistance mutations were detected in samples from 21 (14.6%) of 144 participants; the most frequent mutations were K103N and M184V/I. Phylogenetic analysis identified 11 clusters (2-6 individuals). Clusters included seroconverters only (n=1), prevalent cases and seroconverters (n=4), and prevalent cases only (n=6). Superinfection was identified in one prevalent case and two seroconverters. The annual incidence of superinfection was higher among seroconverters than prevalent cases and was higher than the rate of primary HIV infection in the cohort. Conclusions This report provides important insights into HIV genetic diversity, drug resistance, and superinfection among MSM and TWG in sub-Saharan Africa. These findings may help to inform future HIV prevention interventions in these high-risk groups.