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


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

SUBMITTER: Cillo AR 

PROVIDER: S-EPMC4638139 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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

Cillo Anthony R AR   Hilldorfer Benedict B BB   Lalama Christina M CM   McKinnon John E JE   Coombs Robert W RW   Tenorio Allan R AR   Fox Lawrence L   Gandhi Rajesh T RT   Ribaudo Heather H   Currier Judith S JS   Gulick Roy M RM   Wilkin Timothy J TJ   Mellors John W JW  

AIDS (London, England) 20151001 16


<h4>Background</h4>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.<h4>Design</h4>A5256 was a single-arm trial in which  ...[more]

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