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

• DOI: 10.1128/spectrum.01251-23
• Publication Date: 2023-10-12T13:00:42Z
• Authors: Boitumelo J. L. Zuze; Botshelo T. Radibe; Wonderful T. Choga; Ontlametse T. Bareng; Natasha O. Moraka; Dorcas Maruapula; Kedumetse Seru; Patrick Mokgethi; Baitshepi Mokaleng; Nokuthula Ndlovu; Nametso Kelentse; Molly Pretorius-H...; Roger Shapiro; Shahin Lockman; Joseph Makhema; Vlad Novitsky; Kaelo K. Seatla; Sikhulile Moyo; Simani Gaseitsiwe
• Keywords: drug-resistant mutations (DRMs); Botswana; Genotype; Anti-HIV Agents; HIV-1 C; HIV Infections; fostemsavir (FTR); Microbiology; QR1-502; 3. Good health; Anti-Retroviral Agents; Drug Resistance, Viral; Mutation; HIV-1; entry inhibitors; Humans; polymorphisms; Research Article

ABSTRACT There are limited data on the prevalence of fostemsavir (FTR) resistance-associated polymorphisms in people with HIV Botswana. We sought to determine FTR HIV-1 subtype C sequences from antiretroviral therapy (ART)-naïve and ART-experienced individuals Previously reported literature were surveyed HIV-1C proviral generated a large population-based cohort enrolled between 2013 2018. Sequences ART-naïve included analysis. A total 6,078 participants gp120 this study, 6,030 (99.2%) had known ART status; 1,282 (21.3%) individuals, while 4,748 (78.7%) at study enrollment. Viral load (VL) available for 4,739 (99.8%) whom 4,526 (95.5%) suppressed 213 (4.5%) virologic failure (VF) (VL >400). Among those VF naive, overall resistance was 13.3% (95% CI 11.6%–15.1%) did not differ (29/213, 13.6%) (170/1,282, 13.3%) ( P -value = 0.9). The most predominant mutations (prevalence ≥1.0%) M434I (9.8%), M475I (5.9%), M426L (1.1%). similar both setting no prior exposure. recommend further studies phenotypic impact these guide how monitor resistance. (This has been registered ClinicalTrials.gov under registration no. NCT01965470.) IMPORTANCE Fostemsavir is newly licensed drug that shown have activity against HIV-1. mechanism action different all currently antiretrovirals (ARVs), as such, it offers hope suppression (PWH) who harbor variants used ARVs. Using covering envelope PWH Botswana (ART) naïve well failing ART, we explored polymorphisms. found be setting, Further warranted