Patterns of HIV-1 viral load suppression and drug resistance during the dolutegravir transition: a population-based longitudinal study.
Martin MA., Blenkinsop A., Moffa M., Reynolds SJ., Nalugoda F., Quinn TC., Kigozi G., Ssekubugu R., Gupta RK., Grayson NE., MacIntyre-Cockett G., Kagaayi J., Nakigozi G., Abeler-Dörner L., Fraser C., Ratmann O., Tobian AAR., Laeyendecker O., Moyo S., Kennedy CE., Bonsall D., Galiwango RM., Grabowski MK.
BACKGROUND: Data 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. METHODS: Consenting 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. RESULTS: Among 8,781 people living with HIV (PLHIV), 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 PLHIV, 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 (two-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). CONCLUSIONS: Viral suppression increased during the DTG-transition with minimal emerging intermediate/high-level resistance. Falling resistance among treatment-experienced PLHIV underscores the role of ART adherence in reducing viremia. The emergence of inS153Y justifies continued surveillance.