The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD41 T-cell recovery: A randomized trial

Peter W. Hunt, Nancy S. Shulman, Timothy L. Hayes, Viktor Dahl, M. Somsouk, Nicholas T. Funderburg, Bridget McLaughlin, Alan L. Landay, Oluwatoyin Adeyemi, Lee E. Gilman, Brian Clagett, Benigno Rodriguez, Jeffrey N. Martin, Timothy W. Schacker, Barbara L. Shacklett, Sarah Palmer, Michael M. Lederman, Steven G. Deeks

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

The CCR5 inhibitor maraviroc has been hypothesized to decrease T-cell activation in HIV-infected individuals, but its independent immunologic effects have not been established in a placebo-controlled trial. We randomized 45 HIV-infected subjects with CD4 counts <350 cells per mm3 and plasma HIV RNA levels <48 copies per mL on antiretroviral therapy (ART) to add maraviroc vs placebo to their regimen for 24 weeks followed by 12 weeks on ART alone. Compared with placebo-treated subjects, maraviroc-treated subjects unexpectedly experienced a greater median increase in % CD381HLA-DR1 peripheral blood CD81 T cells at week 24 (12.2% vs 20.7%, P =.014), and less of a decline in activated CD41 T cells (P <.001). The % CD381HLA-DR1 CD41 and CD81 T cells increased nearly twofold in rectal tissue (both P <.001), and plasma CC chemokine receptor type 5 (CCR5) ligand (macrophage-inflammatory protein 1β) levels increased 2.4-fold during maraviroc intensification (P <.001). During maraviroc intensification, plasma lipopolysaccharide declined, whereas sCD14 levels and neutrophils tended to increase in blood and rectal tissue. Although the mechanisms explaining these findings remain unclear, CCR5 ligand-mediated activation of T cells, macrophages, and neutrophils Via alternative chemokine receptors should be explored. These results may have relevance for trials of maraviroc for HIV preexposure prophylaxis and graft-versus-host disease. This trial was registered at www.clinicaltrials.gov as #NCT00735072.

Original languageEnglish (US)
Article number4635
JournalBlood
Volume121
Issue number23
DOIs
StatePublished - Jun 6 2013

Bibliographical note

Publisher Copyright:
© 2013 by The American Society of Hematology.

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