A pilot trial of adding maraviroc to suppressive antiretroviral therapy for suboptimal CD4⁺ T-cell recovery despite sustained virologic suppression: ACTG A5256.

TitleA pilot trial of adding maraviroc to suppressive antiretroviral therapy for suboptimal CD4⁺ T-cell recovery despite sustained virologic suppression: ACTG A5256.
Publication TypeJournal Article
Year of Publication2012
AuthorsWilkin TJ, Lalama CM, McKinnon J, Gandhi RT, Lin N, Landay A, Ribaudo H, Fox L, Currier JS, Mellors JW, Gulick R, Tenorio AR
JournalJ Infect Dis
Volume206
Issue4
Pagination534-42
Date Published2012 Aug 15
ISSN1537-6613
KeywordsAdolescent, Adult, Aged, Aged, 80 and over, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Cyclohexanes, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Triazoles, Viral Load, Young Adult
Abstract

BACKGROUND: Despite viral suppression, antiretroviral therapy (ART) does not restore CD4(+) T-cell counts in many patients infected with human immunodeficiency virus type 1 (HIV-1).

METHODS: In a single-arm pilot trial involving ART recipients with suppressed plasma levels of HIV-1 RNA for at least 48 weeks and stable suboptimal CD4(+) T-cell recovery, subjects added maraviroc, a CCR5 antagonist, to their existing ART for 24 weeks. After stopping maraviroc, they were followed for an additional 24 weeks. A Wilcoxon signed-rank test was used to evaluate whether maraviroc was associated with an increase of at least 20 cells/µL in the CD4(+) T-cell count.

RESULTS: A total of 34 subjects were enrolled. The median age was 50 years, and the median baseline CD4(+) T-cell count was 153 cells/µL. The median increase in CD4(+) T-cell count from baseline to week 22/24 was 12 cells/µL (90% confidence interval, 1-22). A CD4(+) T-cell count increase of at least 20 cells/µL was not detected (P = .97). Markers of immune activation and apoptosis decreased during maraviroc intensification; this decline partially reversed after discontinuing maraviroc.

CONCLUSIONS: Adding maraviroc to suppressive ART for 24 weeks was not associated with an increase in CD4(+) T-cell counts of at least 20 cells/µL. Further studies of CCR5 antagonists in the dampening of immune activation associated with HIV infection are warranted. Clinical Trials Registration. NCT 00709111.

DOI10.1093/infdis/jis376
Alternate JournalJ. Infect. Dis.
PubMed ID22740718
PubMed Central IDPMC3491731
Grant ListAI045008 / AI / NIAID NIH HHS / United States
AI050409 / AI / NIAID NIH HHS / United States
AI050410 / AI / NIAID NIH HHS / United States
AI060354 / AI / NIAID NIH HHS / United States
AI068634 / AI / NIAID NIH HHS / United States
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KL2 RR024977 / RR / NCRR NIH HHS / United States
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