HIV-2 integrase variation in integrase inhibitor-naïve adults in Senegal, West Africa

PLoS One. 2011;6(7):e22204. doi: 10.1371/journal.pone.0022204. Epub 2011 Jul 12.

Abstract

Background: Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance.

Methods: We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2-infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1.

Results: No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein.

Conclusion: Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at "secondary" HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2-infected patients.

Publication types

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

MeSH terms

  • Adult
  • Base Sequence
  • Drug Resistance, Viral / drug effects
  • Drug Resistance, Viral / genetics
  • Female
  • Genetic Variation / drug effects*
  • HIV Integrase / genetics*
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-2 / drug effects
  • HIV-2 / enzymology*
  • HIV-2 / genetics*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Phylogeny
  • Senegal
  • Young Adult

Substances

  • HIV Integrase Inhibitors
  • HIV Integrase

Associated data

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