title: Impact of HIV-1 group O genetic diversity on genotypic resistance interpretation by algorithms designed for HIV-1 group M.
abstract: BACKGROUND
  HIV-1 group O (HIV-O) is characterized by a high genetic divergence from HIV-1 group M viruses. Little is known about the therapeutic impact of this diversity. The aim of this study was to assess in a large series of samples (1) the genotypic impact of natural polymorphism of the HIV-O reverse transcriptase and protease genes; and (2) the predictive value of resistance interpretation algorithms developed for HIV-1 group M when used for highly mutated HIV-O viruses.
  
  
  METHODS
  Sixty-eight antiretroviral-naive and 9 highly antiretroviral-experienced HIV-O-infected patients were included. The viruses were sequenced and resistance-associated mutations were identified using 3 different algorithms (Agence Nationale de Recherches sur le SIDA et les hépatites virales, Rega, Stanford).
  
  
  RESULTS
  All HIV-O samples naturally exhibited the A98G and V179E resistance mutations in the reverse transcriptase region; 54% of samples presented the Y181C mutation, conferring resistance to nonnucleoside reverse transcriptase inhibitors. Twelve minor resistance mutations, present in more than 75% of the protease sequences, led to the different algorithms giving discrepant results for nelfinavir and saquinavir susceptibility. A marked virological response was observed in 8 of the 9 antiretroviral-experienced patients, despite the prediction of limited activity of the combination for 5 to 8 patients according to the algorithm used.
  
  
  CONCLUSIONS
  The high level of natural polymorphism in HIV-O genes, and the important discrepancies between genotypic resistance interpretation and the virological response, emphasize the need for resistance algorithm rules better adapted to HIV-O.
authors.affiliation: Laboratoire associé au Centre National de Référence du VIH, CHU de Rouen, Rouen, France. jean-christophe.plantier@univ-rouen.fr
authors.forename: Agnès
authors.initials: A
authors.lastname: Depatureaux
authors.forename: Charlotte
authors.initials: C
authors.lastname: Charpentier
authors.forename: Marie
authors.initials: M
authors.lastname: Leoz
authors.forename: Guillemette
authors.initials: G
authors.lastname: Unal
authors.forename: Florence
authors.initials: F
authors.lastname: Damond
authors.forename: Anfunbom
authors.initials: A
authors.lastname: Kfutwah
authors.forename: Aurélia
authors.initials: A
authors.lastname: Vessière
authors.forename: François
authors.initials: F
authors.lastname: Simon
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Plantier
mesh_terms: D000465:Algorithms; D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA
chemical_list: D019380:Anti-HIV Agents; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1