Background
African countries have shifted to dolutegravir (DTG)-based first-line HIV treatment. However, population-based studies of resistance trends through DTG roll-out in sub-Saharan Africa are extremely limited.
Methods
We analyzed data from the Rakai Community Cohort Study, an open population-based cohort, during five survey rounds between 2012 and 2022. Consenting people aged 15-49 years were interviewed and provided samples for HIV testing, viral load quantification, and virus deep-sequencing. Sequence data from viremic samples (≥1000 copies/mL) were used to predict intermediate/high-level resistance and identify resistance mutations. The prevalence of resistance was estimated using robust Poisson regression with general estimated equations to account for repeated visits by some participants.
Results
109,328 participant visits were contributed, including 20,383 (26.9%) from PLHIV. Using deep-sequencing data from 4,253 visits, we estimated that the prevalence of NNRTI resistance among pre-treatment viremic participants increased 3.51 (95% CI 2.1–5.9)-fold between the 2012 and 2022 surveys, reaching 16.9 (11.8%–24.2%, Figure 1A). INSTI, NRTI, and PI resistance among pre-treatment viremic participants remained stable and below 2.5% throughout the study. We observe a 3.6 (2.2–6.0)-fold and 7.1 (3.2–15.5)-fold decrease in the prevalence of NNRTI and NRTI resistance among treatment-experienced viremic PLHIV, falling to below 25% in the 2022 survey (Figure 1B). The majority (80.2%, 69.3%–87.3%) of treatment-experienced viremic PLHIV were not resistant to any drug classes in the 2022 survey. INSTI resistance among treatment-experienced viremic PLHIV was minimal throughout, including the 2022 survey (2.9%, 1.0%–8.9%). We observe the inS153Y mutation, which confers 2-fold resistance to DTG, in 5.8% (n=8/139) and 7.4% (n=6/81) of pre-treatment and treatment-experienced viremic participants in the 2022 survey. This mutation was not observed previously.
Conclusions
The roll-out of DTG has not yet reduced the prevalence of NNRTI resistance among pre-treatment PLHIV. However, NNRTI and NRTI resistance among treatment-experienced viremic PLHIV has decreased significantly, potentially due to DTG initiation. Most viremia among treatment-experienced PLHIV is not due to resistance, owing to the importance of engaging PLHIV in care. The sudden recent emergence of inS153Y is concerning and warrants continued monitoring to ensure sustained efficacy of DTG-based therapy.