Virologic and immunologic effects of adding maraviroc to suppressive antiretroviral therapy in individuals with suboptimal CD4+ T-cell recovery.

TitleVirologic and immunologic effects of adding maraviroc to suppressive antiretroviral therapy in individuals with suboptimal CD4+ T-cell recovery.
Publication TypeJournal Article
Year of Publication2015
AuthorsCillo AR, Hilldorfer BB, Lalama CM, McKinnon JE, Coombs RW, Tenorio AR, Fox L, Gandhi RT, Ribaudo H, Currier JS, Gulick RM, Wilkin TJ, Mellors JW
JournalAIDS
Volume29
Issue16
Pagination2121-9
Date Published2015 Oct 23
ISSN1473-5571
Abstract

BACKGROUND: Combination antiretroviral therapy (ART) suppresses HIV-1 replication, but does not restore CD4 T-cell counts in all individuals. To investigate the effects of maraviroc on HIV-1 persistence and the relations between virologic and immunologic parameters in individuals with incomplete CD4 T-cell recovery, we performed a prospective, open-label pilot trial in which maraviroc was added to a suppressive ART regimen for 24 weeks.

DESIGN: A5256 was a single-arm trial in which individuals on suppressive ART with incomplete CD4 T-cell recovery added maraviroc for 24 weeks.

METHODS: We quantified low-level, residual viremia in plasma and total HIV-1 DNA and 2-long terminal repeat (2-LTR) circles in peripheral blood mononuclear cells before and after maraviroc intensification. We also evaluated markers of CD4 and CD8 T-cell immune activation (%CD38HLA-DR) and apoptosis (%caspase3/Bcl-2).

RESULTS: No effect of maraviroc was found on the probability of detectable plasma viremia (≥1 copy/ml; n = 31, exact McNemar P = 1.0) or detectable 2-LTR circles (n = 28, P = 0.25) or on total HIV-1 DNA (n = 28, 90% confidence interval -0.1, +0.3 log10 copies/10 CD4 T-cells). Premaraviroc HIV-1 DNA levels were inversely related to premaraviroc %CD38HLA-DR CD4 T-cells (Spearman = -0.52, P = 0.004), and lower premaraviroc HIV-1 DNA levels were associated with larger decreases in %CD38HLA-DR CD4 T-cells during maraviroc intensification (Spearman = 0.44, P = 0.018).

CONCLUSION: In individuals on suppressive ART with incomplete CD4 T-cell recovery, maraviroc intensification did not affect measures of HIV-1 persistence but did decrease persistent CD4 T-cell immune activation especially in individuals with low preintensification levels of HIV-1 DNA.

DOI10.1097/QAD.0000000000000810
Alternate JournalAIDS
PubMed ID26544577
PubMed Central IDPMC4638139
Grant ListAI068634 / AI / NIAID NIH HHS / United States
AI068636 / AI / NIAID NIH HHS / United States
AI069412-08 / AI / NIAID NIH HHS / United States
AI069419 / AI / NIAID NIH HHS / United States
AI069424 / AI / NIAID NIH HHS / United States
AI069432 / AI / NIAID NIH HHS / United States
AI069439-08 / AI / NIAID NIH HHS / United States
AI069447 / AI / NIAID NIH HHS / United States
AI069452-08 / AI / NIAID NIH HHS / United States
AI069465 / AI / NIAID NIH HHS / United States
AI069471 / AI / NIAID NIH HHS / United States
AI069472 / AI / NIAID NIH HHS / United States
AI069477 / AI / NIAID NIH HHS / United States
AI069484-07 / AI / NIAID NIH HHS / United States
AI069494 / AI / NIAID NIH HHS / United States
AI069496 / AI / NIAID NIH HHS / United States
AI069503-08 / AI / NIAID NIH HHS / United States
AI069511 / AI / NIAID NIH HHS / United States
AI069513 / AI / NIAID NIH HHS / United States
AI069532 / AI / NIAID NIH HHS / United States
AI069534-08 / AI / NIAID NIH HHS / United States
AI069556 / AI / NIAID NIH HHS / United States
AI69418-02 / AI / NIAID NIH HHS / United States
P30AI027757 / AI / NIAID NIH HHS / United States
P30AI045008-15 / AI / NIAID NIH HHS / United States
P30AI050409 / AI / NIAID NIH HHS / United States
P30AI50410 / AI / NIAID NIH HHS / United States
T32 AI007333 / AI / NIAID NIH HHS / United States
T32 AI065380-08 / AI / NIAID NIH HHS / United States
TR000457 / TR / NCATS NIH HHS / United States
U01 AI069494 / AI / NIAID NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1AI068636 / AI / NIAID NIH HHS / United States