title: HIV-2 integrase variation in integrase inhibitor-naïve adults in Senegal, West Africa.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, School of Medicine, University of Washington, Seattle, Washington, United States of America. gottlieb@uw.edu
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Gottlieb
authors.forename: Robert A
authors.initials: RA
authors.lastname: Smith
authors.forename: Ndeye Mery
authors.initials: NM
authors.lastname: Dia Badiane
authors.forename: Selly
authors.initials: S
authors.lastname: Ba
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Hawes
authors.forename: Macoumba
authors.initials: M
authors.lastname: Toure
authors.forename: Alison K
authors.initials: AK
authors.lastname: Starling
authors.forename: Fatou
authors.initials: F
authors.lastname: Traore
authors.forename: Fatima
authors.initials: F
authors.lastname: Sall
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Cherne
authors.forename: Joshua
authors.initials: J
authors.lastname: Stern
authors.forename: Kim G
authors.initials: KG
authors.lastname: Wong
authors.forename: Paul
authors.initials: P
authors.lastname: Lu
authors.forename: Moon
authors.initials: M
authors.lastname: Kim
authors.forename: Dana N
authors.initials: DN
authors.lastname: Raugi
authors.forename: Airin
authors.initials: A
authors.lastname: Lam
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Kiviat
mesh_terms: D000328:Adult; D001483:Base Sequence; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000187:drug effects*; D019427:HIV Integrase / Q000235:genetics*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015498:HIV-2 / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D012675:Senegal; D055815:Young Adult
chemical_list: D019428:HIV Integrase Inhibitors; D019427:HIV Integrase