Raltegravir plasma concentrations in treatment-experienced patients receiving salvage regimens based on raltegravir with and without maraviroc coadministration

Ann Pharmacother. 2010 May;44(5):838-43. doi: 10.1345/aph.1M688. Epub 2010 Apr 6.

Abstract

Background: Raltegravir and maraviroc represent new, important resources for HIV-infected patients with intolerance or resistance to other antiretroviral agents. The safety and efficacy of both drugs have been investigated, but there is no information on possible pharmacokinetic interactions between these 2 drugs in clinical practice.

Objective: To evaluate raltegravir plasma concentrations in heavily treatment-experienced patients receiving salvage regimens and explore, in a preliminary assessment, the potential influence of maraviroc coadministration and other cofactors on raltegravir trough concentrations (C(trough)).

Methods: Fifty-four HIV-infected patients with triple class (nucleoside reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitor, protease inhibitor) treatment experience starting raltegravir 400 mg twice daily, with (n = 11) or without (n = 43) concomitant maraviroc 300 mg twice daily, were evaluated. All regimens included at least 3 drugs of at least 2 different classes. Raltegravir plasma Ctrough, after at least 1 month of treatment, were analyzed to compare groups of patients taking raltegravir only and raltegravir plus maraviroc. Immunovirological (CD4, HIV-RNA) and clinical data after 6 months of treatment were also collected and described.

Results: Raltegravir plasma Ctrough showed a large variability (range <0.020-2.47 microg/mL). Median levels were similar in the 2 groups (raltegravir + maraviroc 0.104 microg/mL, range 0.025-0.826; raltegravir 0.090 microg/mL, range <0.020-2.47, p = 0.400). Detectable (>0.02 microg/mL) raltegravir concentrations were observed in all patients receiving raltegravir + maraviroc and in 74% of patients receiving raltegravir alone (p = 0.060). After 6 months of treatment, the 2 groups had similar clinical, virologic, and immunologic conditions.

Conclusions: Coadministration of maraviroc does not seem to have any relevant effects on raltegravir plasma Ctrough in heavily treatment-experienced patients receiving salvage regimens. Further studies should evaluate the potential additional benefits of maraviroc coadministration in terms of virologic and immunologic response.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / blood*
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • Cohort Studies
  • Cyclohexanes / administration & dosage
  • Cyclohexanes / adverse effects
  • Cyclohexanes / therapeutic use*
  • Drug Administration Schedule
  • Drug Interactions
  • HIV Infections / blood
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Maraviroc
  • Middle Aged
  • Pyrrolidinones / administration & dosage
  • Pyrrolidinones / adverse effects
  • Pyrrolidinones / blood*
  • Pyrrolidinones / therapeutic use
  • Raltegravir Potassium
  • Salvage Therapy*
  • Triazoles / administration & dosage
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*
  • Young Adult

Substances

  • Anti-HIV Agents
  • Cyclohexanes
  • Pyrrolidinones
  • Triazoles
  • Raltegravir Potassium
  • Maraviroc