Clinical utility of maraviroc

Jorge Parra, Joaqun Portilla, Federico Pulido*, Rainel Sãnchez-De La Rosa, Carlos Alonso-Villaverde, Juan Berenguer, Jos L. Blanco, Pere Domingo, Fernando Dronda, Carlos Galera, Flix Gutirrez, Jos M. Kindeln, Hernando Knobel, Manuel Leal, Jose Lpez-Aldeguer, Ana Mario, Celia Miralles, Jos Molt, Enrique Ortega, Jos A. Oteo

*Corresponding author for this work

Research output: Contribution to journalReview articleResearchpeer-review

26 Citations (Scopus)

Abstract

Maraviroc belongs to the family of chemokine (C-C motif) receptor 5 (CCR5) antagonists that prevent the entry of human immunodeficiency virus (HIV) into host CD4 T cells by blocking the CCR5 co-receptor R5. Maraviroc is currently the only CC5R co-receptor inhibitor that has been approved for clinical use in HIV-1-infected patients carrying the CCR5 tropism who are antiretroviral-nave or have experienced therapeutic failure following traditional antiretroviral therapies. This article is a review of the main characteristics of maraviroc and the latest data regarding its clinical application.Maraviroc is effective and well tolerated in pre-treated and antiretroviral-nave patients with HIV-1 infections carrying the CCR5 tropism. Data from the phase III programme of maraviroc, which includes the MOTIVATE 1 and 2 studies and the MERIT study, indicate that maraviroc significantly (p<0.001) increases CD4 cell counts compared with placebo in pre-treated patients and to a similar extent as efavirenz in antiretroviral-nave patients. Even in cases where viral load is not completely suppressed, maraviroc improves immunological response compared with placebo. In addition, promising research suggests that maraviroc has favourable pharmacokinetic and safety profiles in patients with high cardiovascular risk or those co-infected with tuberculosis or hepatitis and could be considered an option for treatment of HIV-infected patients with these co-morbidities. Resistance to maraviroc is low and mainly related to the presence of chemokine (C-X-C motif) receptor 4 (CXCR4) tropism HIV-1-infections or to mutations in the V3 region of glycoprotein (gp) 120; however, the exact mechanisms by which resistance is acquired and their genotypic and phenotypic pattern have not yet been established. It is recommended that a tropism test should be performed when considering maraviroc as an alternate drug in HIV-1-infected patients. Current tropism assays have increased sensitivity to reliably detect CXCR4 HIV with rapid turn-around and at a low cost. Improved detection together with positive data on the drugs efficacy and safety profiles should help physicians to identify more accurately the appropriate candidates for commencement of treatment with maraviroc.In summary, maraviroc improves immunological response and has shown favourable pharmacokinetic and safety profiles in patients with high cardiovascular risk or in those co-infected with tuberculosis or hepatitis. Long-term studies are needed to confirm whether therapeutic expectations resulting from clinical trials with maraviroc translate into a real benefit for HIV-1-infected patients for whom traditional antiretroviral therapies have failed or are not suitable.

Original languageAmerican English
Pages (from-to)527-542
Number of pages16
JournalClinical Drug Investigation
Volume31
Issue number8
DOIs
Publication statusPublished - 2011

Keywords

  • Acquired-immunodeficiency-syndrome
  • Antiretrovirals
  • CCR5-receptor- antagonists
  • Maraviroc.

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