Comparison of the Antiviral Activity of Bictegravir against HIV-1 and HIV-2 Isolates and Integrase Inhibitor-Resistant HIV-2 Mutants

Antimicrob Agents Chemother. 2019 Apr 25;63(5):e00014-19. doi: 10.1128/AAC.00014-19. Print 2019 May.

Abstract

We compared the activity of the integrase inhibitor bictegravir against HIV-1 and HIV-2 using a culture-based, single-cycle assay. Values of 50% effective concentrations ranged from 1.2 to 2.5 nM for 9 HIV-1 isolates and 1.4 to 5.6 nM for 15 HIV-2 isolates. HIV-2 integrase mutants G140S/Q148R and G140S/Q148H were 34- and 110-fold resistant to bictegravir, respectively; other resistance-associated mutations conferred ≤5-fold changes in bictegravir susceptibility. Our findings indicate that bictegravir-based antiretroviral therapy should be evaluated in HIV-2-infected individuals.

Keywords: HIV treatment; HIV-2; West Africa; antiretroviral therapy; bictegravir; drug resistance; human immunodeficiency virus; integrase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Drug Resistance, Viral
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / drug effects*
  • HIV-2 / drug effects*
  • HeLa Cells
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Humans

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 4 or More Rings
  • bictegravir