Maraviroc Intensification of cART in Patients with Suboptimal Immunological Recovery: A 48-Week, Placebo-Controlled Randomized Trial
Authorvan Lelyveld, SFL; Drylewicz, J; Krikke, M; Veel, EM; Otto, SA; Richter, C; Soetekouw, R; Prins, JM; Brinkman, K; Mulder, JW; ...
Source TitlePLoS One
PublisherPUBLIC LIBRARY SCIENCE
University of Melbourne Author/sSymons, Jori
Document TypeJournal Article
Citationsvan Lelyveld, S. F. L., Drylewicz, J., Krikke, M., Veel, E. M., Otto, S. A., Richter, C., Soetekouw, R., Prins, J. M., Brinkman, K., Mulder, J. W., Kroon, F., Middel, A., Symons, J., Wensing, A. M. J., Nijhuis, M., Borghans, J. A. M., Tesselaar, K. & Hoepelman, A. I. M. (2015). Maraviroc Intensification of cART in Patients with Suboptimal Immunological Recovery: A 48-Week, Placebo-Controlled Randomized Trial. PLOS ONE, 10 (7), https://doi.org/10.1371/journal.pone.0132430.
Access StatusOpen Access
OBJECTIVE: The immunomodulatory effects of the CCR5-antagonist maraviroc might be beneficial in patients with a suboptimal immunological response, but results of different cART (combination antiretroviral therapy) intensification studies are conflicting. Therefore, we performed a 48-week placebo-controlled trial to determine the effect of maraviroc intensification on CD4+ T-cell counts and immune activation in these patients. DESIGN: Double-blind, placebo-controlled, randomized trial. METHODS: Major inclusion criteria were 1. CD4+ T-cell count <350 cells/μL while at least two years on cART or CD4+ T-cell count <200 cells/μL while at least one year on cART, and 2. viral suppression for at least the previous 6 months. HIV-infected patients were randomized to add maraviroc (41 patients) or placebo (44 patients) to their cART regimen for 48 weeks. Changes in CD4+ T-cell counts (primary endpoint) and other immunological parameters were modeled using linear mixed effects models. RESULTS: No significant differences for the modelled increase in CD4+ T-cell count (placebo 15.3 CD4+ T cells/μL (95% confidence interval (CI) [1.0, 29.5] versus maraviroc arm 22.9 CD4+ T cells/μL (95% CI [7.4, 38.5] p = 0.51) or alterations in the expression of markers for T-cell activation, proliferation and microbial translocation were found between the arms. However, maraviroc intensification did increase the percentage of CCR5 expressing CD4+ and CD8+ T-cells, and the plasma levels of the CCR5 ligand MIP-1β. In contrast, the percentage of ex-vivo apoptotic CD8+ and CD4+ T-cells decreased in the maraviroc arm. CONCLUSIONS: Maraviroc intensification of cART did not increase CD4+ T-cell restoration or decrease immune activation as compared to placebo. However, ex-vivo T-cell apoptosis was decreased in the maraviroc arm. TRIAL REGISTRATION: ClinicalTrials.gov NCT00875368.
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