title: Lack of primary mutations associated with integrase inhibitors among HIV-1 subtypes B, C, and F circulating in Brazil.
abstract: BACKGROUND
  Antiretroviral drugs targeting integrase (IN) have recently been approved for use in combined and salvage therapeutic interventions.
  
  
  OBJECTIVE
  To evaluate the presence of natural polymorphisms and resistance mutations associated with IN inhibitors among HIV-1 subtypes B, C, and F samples obtained from drug-naive individuals and patients failing highly active antiretroviral therapy in Brazil.
  
  
  METHODS
  Proviral DNA was obtained from blood samples of 105 HIV-1-positive drug-naive patients infected by B, C, or F subtypes and plasma viral RNA from 30 subtype B-infected individuals failing highly active antiretroviral therapy. The IN region was amplified by nested polymerase chain reaction and automatically sequenced for subtype determination. Translated amino acid sequences were inspected for IN mutations associated with antiretroviral resistance.
  
  
  RESULTS
  Eleven mutations described as conferring in vitro resistance to IN strand transfer inhibitors were detected among the HIV-1 Brazilian samples. V72I and V201I were considered as polymorphisms. Major mutations associated with elvitegravir or raltegravir in vivo resistance (Q148K/H/R, N155H) were not detected.
  
  
  CONCLUSIONS
  Although some naturally occurring polymorphisms were observed, the absence of major resistance mutations for the current IN inhibitors provides a good rationale for the introduction of these drugs in Brazil. These results highlight the importance of the continuous surveillance of IN genetic diversity.
authors.affiliation: Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Caroline Bittencourt
authors.initials: CB
authors.lastname: Passaes
authors.forename: Monick Lindenmeyer
authors.initials: ML
authors.lastname: Guimarães
authors.forename: Saada Lima Chequer
authors.initials: SL
authors.lastname: Fernandez
authors.forename: Roberta Dos Santos
authors.initials: Rdos S
authors.lastname: Lorete
authors.forename: Sylvia Lopes Maia
authors.initials: SL
authors.lastname: Teixeira
authors.forename: José Carlos Couto
authors.initials: JC
authors.lastname: Fernandez
authors.forename: Mariza Gonçalves
authors.initials: MG
authors.lastname: Morgado
mesh_terms: D000595:Amino Acid Sequence; D001938:Brazil; D016384:Consensus Sequence; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D024882:Drug Resistance, Viral / Q000235:genetics; D005814:Genes, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D019427:HIV Integrase / Q000235:genetics*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017386:Sequence Homology, Amino Acid
chemical_list: D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase