Prevalence of R5 strains in multi-treated HIV subjects and impact of new regimens including maraviroc in a selected group of patients with CCR5-tropic HIV-1 infection

Int J Infect Dis. 2013 Oct;17(10):e875-82. doi: 10.1016/j.ijid.2013.02.020. Epub 2013 Apr 15.

Abstract

Objectives: Maraviroc currently represents an important antiretroviral drug for multi-experienced and viremic HIV patients. This study focused on two main points: (1) determining the prevalence of R5 and X4 HIV strains in antiretroviral-experienced patients using two main tests currently in use to determine viral tropism, and (2) the follow-up to 3 years of a limited number of patients who started a new antiretroviral protocol including maraviroc.

Methods: A group of 56 HIV patients, previously multi-treated, were first analyzed by genotyping assay and Trofile™ to establish their eligibility for maraviroc treatment. In addition, 25 subjects selected to follow a new therapeutic protocol including a CCR5 antagonist were monitored by HIV RNA viral load and CD4+ cell count.

Results: The determination of viral tropism showed a large percentage of patients with an R5 profile (72% by genotyping assay and 74% by Trofile). The follow-up of most (21 out 25) patients who started the new antiretroviral protocol showed an undetectable viral load throughout the observation period, accompanied by a major improvement in CD4 cell count (cells/mm(3)) (baseline: median CD4 cell count 365, interquartile range (IQR) 204-511; 12 months: median value 501, IQR 349-677, p=0.042; 24 months: median value 503, IQR 386-678, p=0.026; 36 months: median value 601, IQR 517-717, p=0.001). Among the four non-responder subjects, two showed a lack of drug compliance and two switched from R5 to X4.

Conclusion: Although our patient cohort was small, the results showed a high prevalence of R5 viral strains in multi-experienced patients. As well as showing the advantages of genotyping, which can be performed in plasma samples with low viral load replication, the follow-up of HIV patients selected for an alternative drug protocol, including a CCR5 antagonist, showed a persistent undetectable viral replication and a good recovery of CD4 cell count in most treated HIV patients.

Keywords: Genotyping test; HIV; Maraviroc; Trofile™; Tropism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CCR5 Receptor Antagonists
  • Cyclohexanes / pharmacology
  • Cyclohexanes / therapeutic use*
  • Drug Resistance, Viral
  • Drug Substitution
  • Female
  • Follow-Up Studies
  • Genotype
  • HIV Fusion Inhibitors / pharmacology
  • HIV Fusion Inhibitors / therapeutic use*
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology
  • HIV Infections / virology*
  • HIV-1 / physiology*
  • Humans
  • Male
  • Maraviroc
  • Middle Aged
  • Prevalence
  • Receptors, CCR5 / physiology*
  • Sequence Analysis, DNA
  • Treatment Outcome
  • Triazoles / pharmacology
  • Triazoles / therapeutic use*
  • Viral Load / drug effects
  • Viral Tropism
  • Virus Replication
  • Young Adult

Substances

  • CCR5 Receptor Antagonists
  • CCR5 protein, human
  • Cyclohexanes
  • HIV Fusion Inhibitors
  • Receptors, CCR5
  • Triazoles
  • Maraviroc