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

Abstract

Background Maintaining 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. Methods We 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. Results Among 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. Conclusion Among 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.