Virological response after short-term CCR5 antagonist exposure in HIV-infected patients: frequency of subjects with virological response and associated factors

Antimicrob Agents Chemother. 2011 Oct;55(10):4664-9. doi: 10.1128/AAC.00753-11. Epub 2011 Aug 1.

Abstract

The virological response after an 8-day maraviroc monotherapy has been proposed to be an alternative method to determine whether an CCR5 antagonist should be prescribed to HIV-infected patients. The frequency of patients eligible for a combined antiretroviral therapy which includes maraviroc on the basis of the result of this clinical test is not well-known at the moment. In the same way, clinical and immunovirological factors associated with the virological response after antagonist exposure need to be determined. Ninety consecutive HIV-infected patients were exposed to an 8-day maraviroc monotherapy. The virological response was considered positive if either a reduction of ≥1-log(10) HIV RNA copies/ml or an undetectable viral load (<40 HIV RNA copies/ml) was achieved. CXCR4- and CCR5-tropic virus levels were determined by using patients' viral isolates and multiple rounds of infection of indicator cell lines (U87-CXCR4 and U87-CCR5). The frequency of patients with a positive virological response was 72.2% (94.7% and 66.2% for treatment-naïve and pretreated patients, respectively). The positive response rates dramatically decreased in patients with lower CD4(+) T-cell counts. The CXCR4-tropic virus level was the only variable independently associated with the virological response after short-term maraviroc exposure. Lower CD4(+) T-cell strata were associated with higher CXCR4-tropic virus levels. These results support the suggestion that CCR5 antagonists should be an early treatment option before the expansion of CXCR4-tropic strains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • CCR5 Receptor Antagonists*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects
  • Cell Line
  • Cyclohexanes / administration & dosage
  • Cyclohexanes / pharmacology
  • Cyclohexanes / therapeutic use*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • Humans
  • Male
  • Maraviroc
  • Middle Aged
  • RNA, Viral / blood
  • Receptors, CXCR4 / blood
  • Triazoles / administration & dosage
  • Triazoles / pharmacology
  • Triazoles / therapeutic use*
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents
  • CCR5 Receptor Antagonists
  • CXCR4 protein, human
  • Cyclohexanes
  • RNA, Viral
  • Receptors, CXCR4
  • Triazoles
  • Maraviroc