Low rates of NRTI and NNRTI drug resistance among participants in the Botswana combination prevention program (BCPP) trial

BACKGROUND:Scale-up of antiretroviral therapy (ART) and introduction of treat-all strategy necessitates population-level monitoring of acquired HIV drug resistance (ADR) and pre-treatment drug resistance (PDR) mutations. METHODS:Blood samples were collected from 4,973 HIV-positive individuals residing in 30 communities across Botswana who participated in the Botswana Combination Prevention Project (BCPP) in 2013–2018. HIV sequences were obtained by long-range HIV genotyping. Major drug-resistance mutations (DRMs) and surveillance drug resistance mutations (SDRMs) associated with nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) were analyzed according to the Stanford University HIV Drug Resistance Database. Viral sequences were screened for G-to-A hypermutations (HM). A threshold of 2% was used for HM adjustment. Viral suppression was considered at HIV-1 RNA load ≤400 copies/mL. RESULTS:Among 4,973 participants with HIV-1C sequences, ART data were available for 4,927 (99%) including 3,858 (78%) on ART. Among those on ART, 3,435 had viral load data and 3,297 (96%) were virologically suppressed. Among 1069 (22%) HIV-infected individuals not on ART, we found NRTI- and NNRTI-associated SDRMs were found in 1.5% (95% confidence interval (CI)1.0–2.5%) and 2.9% (95% CI2.0–4.2%), respectively. Of the 138 (4%) of individuals who had detectable HIV-1 RNA, we found NRTI- and NNRTI-associated drug resistance mutations in 16% (95% CI10–25%) and 33% (95% CI25–42%), respectively. CONCLUSIONS:We found a low prevalence of NRTI- and NNRTI-associated PDR-resistance mutations among residents of rural and peri-urban communities across Botswana. However, individuals on ART with detectable virus had ADR NRTI and NNRTI mutations above 15%.