Primary resistance to maraviroc in a large set of R5-V3 viral sequences from HIV-1-infected patients

J Antimicrob Chemother. 2010 Dec;65(12):2502-4. doi: 10.1093/jac/dkq381. Epub 2010 Oct 12.

Abstract

Objectives: Evaluation of the prevalence of V3 mutational patterns associated with maraviroc resistance in R5-using variants.

Methods: V3 sequences were obtained from 809 plasma specimens collected from maraviroc-naive HIV-1-infected individuals on regular follow-up at Hospital Carlos III. Sequences considered to harbour R5-tropic viruses were examined for the presence of primary maraviroc resistance mutational patterns, as found in both in vitro and in vivo studies.

Results: A total of 498 R5-V3 sequences were identified. They belonged to recent HIV-1 seroconverters (55.6%), chronically antiretroviral-naive subjects (20.1%) and antiretroviral-experienced patients (24.3%). Most individuals (93.8%) were infected with HIV-1 subtype B. The overall prevalence of maraviroc resistance mutational patterns was low (≤5%). Likewise, specific polymorphisms 4L, 11R or 19S, recently found to be associated with lower clinical response to maraviroc, were found in <2% of tested samples. The rate of maraviroc resistance patterns did not differ significantly according to length of HIV-1 infection, antiretroviral exposure or HIV-1 subtype.

Conclusions: The prevalence of maraviroc resistance mutations is low in maraviroc-naive HIV-1-infected individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Cyclohexanes / pharmacology*
  • Cyclohexanes / therapeutic use
  • Drug Resistance, Viral / genetics*
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / genetics*
  • HIV Envelope Protein gp120 / metabolism
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Seropositivity / drug therapy
  • HIV Seropositivity / virology
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / physiology
  • Humans
  • Maraviroc
  • Mutation
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics*
  • Peptide Fragments / metabolism
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism*
  • Sequence Analysis, DNA
  • Triazoles / pharmacology*
  • Triazoles / therapeutic use
  • Viral Tropism

Substances

  • Anti-HIV Agents
  • Cyclohexanes
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments
  • Receptors, CCR5
  • Triazoles
  • Maraviroc