PLoS ONE (Jan 2011)

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

  • Geoffrey S Gottlieb,
  • Robert A Smith,
  • Ndeye Mery Dia Badiane,
  • Selly Ba,
  • Stephen E Hawes,
  • Macoumba Toure,
  • Alison K Starling,
  • Fatou Traore,
  • Fatima Sall,
  • Stephen L Cherne,
  • Joshua Stern,
  • Kim G Wong,
  • Paul Lu,
  • Moon Kim,
  • Dana N Raugi,
  • Airin Lam,
  • James I Mullins,
  • Nancy B Kiviat,
  • Papa Salif Sow for the UW-Dakar HIV-2 Study Group

DOI
https://doi.org/10.1371/journal.pone.0022204
Journal volume & issue
Vol. 6, no. 7
p. e22204

Abstract

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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.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.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.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.