Effect of maraviroc intensification on HIV-1-specific T cell immunity in recently HIV-1-infected individuals

PLoS One. 2014 Jan 27;9(1):e87334. doi: 10.1371/journal.pone.0087334. eCollection 2014.

Abstract

Background: The effect of maraviroc on the maintenance and the function of HIV-1-specific T cell responses remains unknown.

Methods: Subjects recently infected with HIV-1 were randomized to receive anti-retroviral treatment with or without maraviroc intensification for 48 weeks, and were monitored up to week 60. PBMC and in vitro-expanded T cells were tested for responses to the entire HIV proteome by ELISpot analyses. Intracellular cytokine staining assays were conducted to monitor the (poly)-functionality of HIV-1-specific T cells. Analyses were performed at baseline and week 24 after treatment start, and at week 60 (3 months after maraviroc discontinuation).

Results: Maraviroc intensification was associated with a slower decay of virus-specific T cell responses over time compared to the non-intensified regimen in both direct ex-vivo as well as in in-vitro expanded cells. The effector function profiles of virus-specific CD8⁺ T cells were indistinguishable between the two arms and did not change over time between the groups.

Conclusions: Maraviroc did not negatively impact any of the measured parameters, but was rather associated with a prolonged maintenance of HIV-1-specific T cell responses. Maraviroc, in addition to its original effect as viral entry inhibitor, may provide an additional benefit on the maintenance of virus-specific T cells which may be especially important for future viral eradication strategies.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Retroviral Agents / pharmacology*
  • Cyclohexanes / pharmacology*
  • Cytokines / analysis
  • Enzyme-Linked Immunospot Assay
  • Flow Cytometry
  • HIV Infections / immunology*
  • HIV-1*
  • Humans
  • Immunity, Cellular / drug effects*
  • Maraviroc
  • Receptors, CCR5 / metabolism
  • Statistics, Nonparametric
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Triazoles / pharmacology*
  • Virus Internalization / drug effects

Substances

  • Anti-Retroviral Agents
  • Cyclohexanes
  • Cytokines
  • Receptors, CCR5
  • Triazoles
  • Maraviroc

Grants and funding

This work was funded by HIVACAT, the Catalan program for the development of therapeutic and preventive HIV vaccines, the European AIDS Treatment Network (NEAT – FP6, contract LSHP-CT- 2006-037570) and Pfizer Inc, and an unrestricted grant from ViiV to support the sub-study to the original Maraviboost clinical phase III trial, which was also sponsored by ViiV. The Hospital Clinic-IDIBAPS cohort was supported in part by the “Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Madrid (Spain),” Spanish Network for AIDS Research (RIS; ISCIII-RETIC RD06/006). A.K-T was funded by the Japan Society for the Promotion of Science for the “Institutional Program for Young Researcher Overseas Visits.” The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.