The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ 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 Shacklett, Sarah Palmer, Michael M. Lederman, Steven G. Deeks

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86 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 mm(3) 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 % CD38+HLA-DR+ peripheral blood CD8+ T cells at week 24 (+2.2% vs -0.7%, P = .014), and less of a decline in activated CD4+ T cells (P < .001). The % CD38+HLA-DR+ CD4+ and CD8+ 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)
Pages (from-to)4635-4646
Number of pages12
JournalBlood
Volume121
Issue number23
DOIs
StatePublished - Jun 6 2013

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ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Hunt, P. W., Shulman, N. S., Hayes, T. L., Dahl, V., Somsouk, M., Funderburg, N. T., McLaughlin, B., Landay, A. L., Adeyemi, O., Gilman, L. E., Clagett, B., Rodriguez, B., Martin, J. N., Schacker, T. W., Shacklett, B., Palmer, S., Lederman, M. M., & Deeks, S. G. (2013). The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial. Blood, 121(23), 4635-4646. https://doi.org/10.1182/blood-2012-06-436345