Fostemsavir resistance-associated polymorphisms in HIV-1 subtype C in a large cohort of treatment-naive and treatment-experienced individuals in Botswana

There are limited data on the prevalence of fostemsavir (FTR) resistance-associated polymorphisms in people with HIV in Botswana. We sought to determine the prevalence of FTR resistance-associated polymorphisms in HIV-1 subtype C sequences from antiretroviral therapy (ART)-naive and ART-experienced individuals in Botswana. Previously reported FTR resistance-associated polymorphisms from literature were surveyed from HIV-1C proviral sequences generated from a large HIV-1 population-based cohort enrolled between 2013 and 2018. Sequences from ART-naive and ART-experienced individuals were included in the analysis. A total of 6,078 participants with gp120 sequences were included in this study, and 6,030 (99.2%) had known ART status; 1,282 (21.3%) were from ART-naive individuals, while 4,748 (78.7%) were from individuals on ART at study enrollment. Viral load (VL) data were available for 4,739 (99.8%) ART-experienced individuals, of whom 4,526 (95.5%) were suppressed and 213 (4.5%) had virologic failure (VF) (VL >400). Among those with VF and ART naive, the overall prevalence of FTR resistance was 13.3% (95% CI 11.6%-15.1%) and did not differ between ART-experienced with VF individuals (29/213, 13.6%) and ART-naive individuals (170/1,282, 13.3%) (P-value = 0.9). The most predominant mutations (prevalence >= 1.0%) were M434I (9.8%), M475I (5.9%), and M426L (1.1%). The overall prevalence of FTR polymorphisms was similar in both ART-naive and ART-experienced individuals with VF in a setting with no prior FTR exposure. We recommend further studies on the phenotypic impact of these polymorphisms to guide how to monitor for FTR resistance. (This study has been registered at ClinicalTrials.gov under registration no. NCT01965470.)