Prevalence of Drug Resistance Mutations and their Association with Time to Virological Failure in People Living with HIV in Uganda

Introduction: Despite advancements in antiretroviral therapy (ART), virological failure and drug resistance mutations (DRMs) continue to pose major challenges, especially in resource-limited settings. This study examined DRM prevalence and their association with time to virological failure, informing strategies to optimize HIV treatment outcomes. Methods This cohort study retrospectively reviewed medical records of 235 People living with HIV (PLHIV) who underwent HIV drug resistance testing at the Mildmay-Uganda Hospital from 2018–2023. Data on demographics, ART, and DRMs were analyzed. Kaplan-Meier and log-rank tests were used to compare median survival times (virological failure). Cox proportional hazards models assessed associations factors associated with time to virological failure, with significance set at p  < 0.05. Results Participants had a mean age of 28.0 years, 11.2 years on ART, and DRMs detected in 59.6%. Mutation prevalence was NNRTIs (52.8%), NRTIs (50.2%), PI major (25.5%), and INSTI (≤ 0.9%). Key drug class mutations included, NNRTIs (K103KN 25.1%, G190AS 14.0%, Y181CF/V/F 12.3%), NRTIs (M184V 45.0%, T215FY 30.2%, M41L 18.3%), PIs (M46I 15.7%, V82VA 12.3%, I54LV 9.4%), and INSTIs (E138K, T66A, G118R, E92EV all at 0.4%). DRMs were significantly associated with longer time (months) to virological failure: NRTIs (129.3 vs. 88.2, p  = 0.008), NNRTIs (127.4 vs. 84.2, p  = 0.003), and PIs (170.9 vs. 88.7, p  = 0.000). In cox regression analysis, time to virological failure was significantly associated with age (HR: 0.987; CI: 0.976–0.998; p = 0.019, aHR: 0.976; CI: 0.959–0.993; p = 0.007), ART duration (HR: 0.828; CI: 0.800–0.856; p = 0.000, aHR: 0.827; CI: 0.792–0.863; p = 0.000), drug mutations; NRTI (HR: 0.659; CI: 0.484–0.898; p = 0.008), NNRTI (HR: 0.628; CI: 0.463–0.851; p = 0.003), and PI (HR: 0.257; CI: 0.146–0.453; p = 0.000, aHR: 0.337; CI: 0.137–0.831; p = 0.018). Conclusion Drug resistance is common among PLHIV failing ART, dominated by NNRTI and NRTI mutations. DRMs were present among PLHIV who took a longer time to virological failure. Delayed failure was independently associated with older age, longer ART duration, and PI mutations. Findings support early DRM testing and individualized ART, especially as newer ART options emerge.