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

Microbiol Spectr. 2023 Dec 12;11(6):e0125123. doi: 10.1128/spectrum.01251-23. Epub 2023 Oct 12.

Abstract

Fostemsavir (FTR) is a newly licensed antiretroviral drug that has been shown to have activity against HIV-1. The mechanism of action of FTR is different from all currently available antiretrovirals (ARVs), and as such, it offers hope for HIV-1 suppression in those people with HIV (PWH) who harbor HIV-1 variants with drug resistance mutations to currently used ARVs. Using 6,030 HIV-1 sequences covering the HIV-1 envelope from PWH in Botswana who are antiretroviral therapy (ART) naïve as well as those who are failing ART, we explored the sequences for FTR resistance-associated polymorphisms. We found the prevalence of FTR polymorphisms to be similar in both ART-naïve and ART-experienced individuals with VF in this setting, with no prior FTR exposure. Further studies on the phenotypic impact of these polymorphisms are warranted to guide how to monitor for FTR resistance.

Keywords: Botswana; HIV-1 C; drug-resistant mutations (DRMs); entry inhibitors; fostemsavir (FTR); polymorphisms.

MeSH terms

  • Anti-HIV Agents* / pharmacology
  • Anti-HIV Agents* / therapeutic use
  • Anti-Retroviral Agents / therapeutic use
  • Botswana
  • Drug Resistance, Viral / genetics
  • Genotype
  • HIV Infections* / drug therapy
  • HIV-1* / genetics
  • Humans
  • Mutation

Substances

  • fostemsavir
  • Anti-HIV Agents
  • Anti-Retroviral Agents