HIV-1 Subtype–Specific Distribution of Genotypic Drug Resistance Mutations Among Patients with Advanced HIV Disease Failing First-Line ART in Homa Bay, Kenya

HIV-1 genetic diversity may influence the selection of antiretroviral drug resistance mutations (DRMs); however, subtype-specific resistance patterns remain incompletely characterized in East Africa, where subtype A1 predominates. We examined the distribution of genotypic DRMs across HIV-1 subtypes among patients with advanced HIV disease failing NNRTI-based first-line therapy in western Kenya. In this cross-sectional molecular sub-analysis, 65 hospitalized individuals (≥15 years) with virological failure (HIV-1 RNA ≥1000 copies/mL) had a 1,084-bp pol gene fragment sequenced. Subtypes were assigned using REGA. DRMs were identified using the Stanford HIV Drug Resistance Database. Associations between subtype and specific mutations were evaluated using Fisher’s exact test. Subtype A1 dominated (70.8%), followed by D (13.8%), recombinants (9.2%), and A2 (6.2%). We detected dual-class resistance in 73.8% of participants. The most frequent mutations were M184V (64.6%) and K103N/S (60.0%). Subtype A1 sequences were less frequently observed to have K101E/H (8.7%, p=0.011) and Y181C/I/V (17.4%, p=0.027) than non-A1 subtypes. No significant associations were observed between subtype and NRTI mutations. These findings suggest possible subtype-associated differences in NNRTI resistance patterns that warrant validation in larger studies, underscoring the importance of continued molecular surveillance to guide resistance monitoring and optimize long-term treatment strategies in the era of integrase inhibitor–based therapy.