BackgroundData on the population-scale impact of dolutegravir (DTG)-based HIV regimens in sub-Saharan Africa are extremely limited. We used data from a surveillance cohort in southern Uganda to assess viral suppression and antiretroviral (ART) resistance over 10-years alongside DTG scale-up.MethodsConsenting participants in the population-based Rakai Community Cohort Study between August 2011 and March 2023 aged 15-49 completed questionnaires and provided samples for HIV testing, viral load quantification, and viral deep-sequencing. We collected data on DTG utilization at HIV care clinics. We estimated the prevalence of HIV suppression and ART resistance using robust Poisson regression. Bayesian logistic regression quantified associations between resistance and individual-level suppression across surveys.ResultsAmong 8781 people with HIV (PWH), suppression increased from 57.1% (2014, 95% confidence interval [CI], 55.4%-58.8%) to 90.3% (2022, 95% CI, 89.2%-91.4%). By 2020 84.4% (95% CI, 83.7%-85.2%) and 64.6% (95% CI, 63.9%-65.3%) of men and women on ART were on DTG. Among treatment-experienced viremic PWH, any intermediate/high resistance decreased from 51.1% (95% CI, 40.7%-64.2%, 2014) to 27.9% (95% CI, 21.3%-36.5%, 2022). Two of 258 (0.8%) 2022 participants harbored intermediate/high-level DTG resistance (inQ148R, inE138K, and inG140A). inS153Y (2-fold INSTI resistance) was observed in 23/306 (7.5%) of viremic individuals, with evidence of transmission. By 2022, NNRTI/NRTI resistance was not associated with a reduction in individual-level suppression (risk ratios: 1.15, 95% HPD: 0.93-1.39; 1.14, 0.86-1.42).ConclusionsViral suppression increased during the DTG transition with minimal emerging intermediate/high-level resistance. Falling resistance among treatment-experienced PWH underscores the role of ART adherence in reducing viremia. The emergence of inS153Y justifies continued surveillance.