MK-8591 (4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine) Exhibits Potent Activity against HIV-2 Isolates and Drug-Resistant HIV-2 Mutants in Culture

Antimicrob Agents Chemother. 2017 Jul 25;61(8):e00744-17. doi: 10.1128/AAC.00744-17. Print 2017 Aug.

Abstract

There is a pressing need to identify more effective antiretroviral drugs for HIV-2 treatment. Here, we show that the investigational compound MK-8591 (4'-ethynyl-2-fluoro-2'-deoxyadenosine [EFdA]) is highly active against group A and B isolates of HIV-2; 50% effective concentrations [EC50] for HIV-2 were, on average, 4.8-fold lower than those observed for HIV-1. MK-8591 also retains potent activity against multinucleoside-resistant HIV-2 mutants (EC50 ≤ 11 nM). These data suggest that MK-8591 may have antiviral activity in HIV-2-infected individuals.

Keywords: 4′-ethynyl-2-fluoro-2′-deoxyadenosine; EFdA; HIV-1; HIV-2; MK-8591; NRTI; antiretroviral therapy; drug resistance.

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Deoxyadenosines / pharmacology*
  • Drug Resistance, Viral / genetics
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV-1 / drug effects*
  • HIV-1 / isolation & purification
  • HIV-2 / drug effects*
  • HIV-2 / genetics
  • HIV-2 / isolation & purification
  • Humans
  • Microbial Sensitivity Tests
  • Reverse Transcriptase Inhibitors / pharmacology*

Substances

  • Anti-HIV Agents
  • Deoxyadenosines
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • islatravir