Speaker
Description
Viral resistance to the efficacy of antiretroviral therapy (ART) has the potential to lead to a resurgence in HIV incidence and death among people living with HIV (PLHIV). To date, there have been no longitudinal, population-based studies of HIV drug resistance trends during ART program expansion in sub-Saharan Africa. We analyzed epidemiological and virological data collected from 93,659 participant visits between 2012 and 2018 collected as part of the open population-based Rakai Community Cohort Study. Consenting participants aged 15-49 years were tested for HIV and completed questionnaires. PLHIV provided samples for viral load quantification and virus deep-sequencing, which was used to predict resistance profiles. The prevalence of class-specific resistance and resistance-conferring substitutions were estimated using robust Poisson regression using inverse probability weighting to account for missing sequence data among some participants. Using deep-sequencing data from 3,709 pre-treatment participant visits, we estimated that between 2012 and 2017 the population prevalence of non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), and protease inhibitor (PI) resistance among all PLHIV decreased significantly (prevalence ratio (PR): 0.38, 95% CI 0.25 – 0.57; 0.20, 95% CI 0.09 – 0.45; 0.19, 95% CI 0.09 – 0.39, respectively). However, among viremic pre-treatment PLHIV, the prevalence of NNRTI resistance increased two-fold (PR = 1.96, 95% CI 1.31-2.94) to 9.8% (7.4% - 13.0%) over the same time period, of which 78.3% was monoresistance. Using data from 417 viremic treatment-experienced PLHIV, we estimated that the 2017 prevalence of NNRTI and NRTI resistances were 47.7% (95% CI 40.9% - 55.5%) and 36.6% (95% CI 30.1% - 44.3%, Figure 1B), respectively, of which 75.6% was NNRTI/NRTI dual-class resistance. In 2017, 10.1% (95% CI 7.7%-13.3%) and 10.2% (95% CI 6.6%-15.6%) of viremic pre-treatment and treatment-experienced PLHIV harbored the compensatory mutation inT97A. The prevalence of inT97A warrants heightened surveillance considering the recent roll-out of dolutegravir-based regimens.
