HIV viral non-suppression and drug resistance among persons who inject drugs on dolutegravir antiretroviral therapy in Kenya

BackgroundMaintaining viral suppression among people who inject drugs (PWID) living with HIV in sub-Saharan Africa remains critical to minimize drug resistance for dolutegravir (DTG)-based regimens. We evaluated PWID taking DTG to assess longitudinal rates of viral non-suppression and emergence of drug resistance mutations in Kenya. MethodsWe enrolled Kenyan PWID who had transitioned from an efavirenz (EFV) based regimen to tenofovir+lamivudine+DTG (TLD) [≥]6 months prior, and measured plasma HIV RNA viral load (VL) every 6 months for 2 years. We used univariable Cox proportional hazards to assess longitudinal risk for viremia (VL >200 copies/ml). Plasma specimens with viremia were genotyped for HIV drug resistance, including minority variants, using a lab-developed PacBio sequencing assay, and referenced by the Stanford HIVdb program. ResultsAmong 250 participants, 125 were receiving methadone, 199 (79.6) reported heroin use, 70% were male, and median age was 39 years. 194 (77.6%) participants completed all five study visits, 41 (16.4%) were lost to follow-up and 15 (6.0%) died. Across all study visits, 166 (66.0%) of the 250 participants were always suppressed, and 84 (33.6%) were viremic at least once during follow-up, including 8 (3.2%) who were always viremic and 76 (30.4%) who were intermittently suppressed. Living in an improvised shelter or outdoors was significantly associated with a higher risk of viremia (HR=4.35, 95% CI: 1.52-12.53). 93 specimens had drug resistance genotyping, 27 (29%) of which were from participants with incomplete follow-up. NNRTI resistance was frequent (37-41% across visits), whereas major resistance mutations were infrequent to tenofovir (4.3%), lamivudine (7.5%), and DTG (1%, minority variant S153F detected at 1% frequency). Accessory DTG mutations, which do not independently reduce susceptibility, were more common, observed in 41% (38/93) of genotyped specimens, most often T97A, E138K, and L74M. ConclusionAmong PWID living with HIV on TLD in Kenya, one-third had intermittent or sustained viral non-suppression across two years of follow-up. While NNRTI resistance was common, DTG resistance mutations were rare. Improving viral suppression among PWID living with HIV will reduce transmission risks and improve clinical outcomes.