title: HIV integrase variability and genetic barrier in antiretroviral naïve and experienced patients.
abstract: BACKGROUND
  HIV-1 integrase (IN) variability in treatment naïve patients with different HIV-1 subtypes is a major issue. In fact, the effect of previous exposure to antiretrovirals other than IN inhibitors (INI) on IN variability has not been satisfactorily defined. In addition, the genetic barrier for specific INI resistance mutations remains to be calculated.
  
  
  METHODS
  IN variability was analyzed and compared with reverse transcriptase (RT) and protease (PR) variability in 41 treatment naïve and 54 RT inhibitor (RTI) and protease inhibitor (PRI) experienced patients from subjects infected with subtype B and non-B strains. In addition, four HIV-2 strains were analyzed in parallel. Frequency and distribution of IN mutations were compared between HAART-naïve and RTI/PI-experienced patients; the genetic barrier for 27 amino acid positions related to INI susceptibility was calculated as well.
  
  
  RESULTS
  Primary mutations associated with resistance to INI were not detected in patients not previously treated with this class of drug. However, some secondary mutations which have been shown to contribute to INI resistance were found. Only limited differences in codon usage distribution between patient groups were found. HIV-2 strains from INI naïve patients showed the presence of both primary and secondary resistance mutations.
  
  
  CONCLUSIONS
  Exposure to antivirals other than INI does not seem to significantly influence the emergence of mutations implicated in INI resistance. HIV-2 strain might have reduced susceptibility to INI.
authors: Molecular Virology Unit, Virology and Microbiology Department, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.
authors: Antonio
authors: A
authors: Piralla
authors: Stefania
authors: S
authors: Paolucci
authors: Roberto
authors: R
authors: Gulminetti
authors: Giuditta
authors: G
authors: Comolli
authors: Fausto
authors: F
authors: Baldanti
mesh_terms: D024882:Drug Resistance, Viral; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000145:classification / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D019428:HIV Integrase Inhibitors; D019427:HIV Integrase