Characteristics of HIV drug resistance mutations among antiretroviral therapy–experienced adolescents living with HIV in South Rift Valley, Kenya: A retrospective cohort study

Antiretroviral therapy (ART) has significantly improved survival of people living with HIV, yet drug resistance mutations (DRM) threaten global treatment success. In Kenya, HIV remains a leading cause of mortality among adolescents with poorer viral suppression than children or adults. Although treatment regimens shifted in 2018 with the introduction of dolutegravir, data on DRM in South Rift Valley (SRV) remains limited. We aimed to characterize patterns, proportions, and types of DRM among ART-experienced adolescents aged 10–19 years in SRV. A retrospective study was conducted among 226 ART-experienced adolescents across 82 clinics in Nandi, Kericho, Bomet, and Narok counties, selected through simple random sampling. Blood samples underwent genotypic resistance testing; plasma HIV RNA was extracted using Viral RNA/DNA Mini Kit, reverse-transcribed to cDNA, and PCR-amplified targeting pol gene protease and reverse transcriptase regions. Sequences compared with a reference HIV strain and analyzed using Stanford HIV Drug Resistance database. Overall, 145 (64%) adolescents with high viral loads exhibited resistance. Participants had a mean age of 16.3 years (SD = 2.7); 51.3% were male and 65% orphans. Dual resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) occurred in 53%, while resistance to protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were 9.3% and 7.1%, respectively. NNRTIs resistance was highest to NVP (50.4%) and EFV (49.6%), commonly driven by K103N (23.9% and 28.8%). NRTI resistance included 3TC (40%, M184V 31%), AZT (20%, M184V 5.8%), ABC (26.3%, M184V 13.3%), and TDF (2.7%, M184V 1.8%). PI resistance featured ATV/r (V82A, L33F), DRV/r (L89V), and LPV/r (V82A). INSTI resistance included DTG, CAB, and RAL with S230R, G118R, R263K, and Y143R mutations. High levels of resistance to NNRTIs and NRTIs, combined with emerging PIs and INSTIs resistance, underscore urgent need for routine resistance monitoring and updated treatment guidelines for adolescents living with HIV in Kenya.