title: HIV-2 protease sequences of subtypes A and B harbor multiple mutations associated with protease inhibitor resistance in HIV-1.
abstract: BACKGROUND
  HIV-1 protease inhibitors (PI) have been used for treating HIV-2-infected persons but little is known about amino acid mutations associated with PI resistance in HIV-2 and whether they are similar to those seen in HIV-1.
  
  
  OBJECTIVE
  To determine the frequency of HIV-1 PI resistance-associated mutations in PI-naive HIV-2-infected individuals.
  
  
  METHODS
  Using PCR, protease genes were amplified from 76 individuals, directly sequenced, phylogenetically subtyped, and translated into amino acids to analyze PI-associated major and minor mutations.
  
  
  RESULTS
  Of the 76 HIV-2 sequences, 68% belonged to subtype A and 32% to subtype B. All sequences contained at least four codon changes giving substitutions at 10, 30, 32, 36, 46, 47, 71 or 77. The frequency of these mutations was similar in subtype A and B viruses. Two major resistance-conferring mutations, 30N and 46I, were identified in one (1%) and 68 (89%) specimens, respectively. Minor mutations 10V/I, 32I, 36I, 47V, and 71V were predominant (89%-100%), followed by the rare mutation 77I (1%). Of the 76 strains, 89% harbored multiple PI resistance-associated substitutions comprising both the major 46I and minor mutations: 10V/I, 32I, 36I, 46I, 47V, 71V (76%); 10V, 32I, 36I, 46I, 47V (9%); and 10V, 32I, 36I, 46I, 47V 71V, 77I (1.3%), 10V, 32I, 46I, 47V, 71V (1.3%), and 10V, 30N, 32I, 36I, 46I, 47V, 71V (1.3%). The remaining 11% of the sequences had patterns with only minor mutations: 10V, 32I, 36I, 47V, 71V (9%) and 10V, 32I, 36I, 47V (1.3%).
  
  
  CONCLUSIONS
  The high frequency of multiple PI-associated substitutions represent natural polymorphisms occurring in HIV-2 strains of subtypes A and B. Phenotypic and clinical studies are needed to determine the relevance of these substitutions.
authors.affiliation: HIV and Retrovirology Branch and the Office of the Director, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Atlanta, Georgia, USA.
authors.forename: Danuta
authors.initials: D
authors.lastname: Pieniazek
authors.forename: Mark
authors.initials: M
authors.lastname: Rayfield
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Hu
authors.forename: John N
authors.initials: JN
authors.lastname: Nkengasong
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Walid
authors.initials: W
authors.lastname: Heneine
authors.forename: Clement
authors.initials: C
authors.lastname: Zeh
authors.forename: Simon M
authors.initials: SM
authors.lastname: Agwale
authors.forename: Charles
authors.initials: C
authors.lastname: Wambebe
authors.forename: Liliana
authors.initials: L
authors.lastname: Odama
authors.forename: Stefan Z
authors.initials: SZ
authors.lastname: Wiktor
mesh_terms: D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D014644:Genetic Variation; D015658:HIV Infections / Q000821:virology*; D016333:HIV Protease; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D015498:HIV-2 / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny
chemical_list: D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; C065184:p16 protease, Human immunodeficiency virus 2