Impact of antiretroviral therapy intensification with C-C motif chemokine receptor 5 antagonist maraviroc on HIV-associated neurocognitive impairment.

AIDS (London, England) 2023 Nov 01

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Chemokine receptor CCR5 is the principal co-receptor for entry of M-tropic HIV virus into immune cells. It is expressed in the central nervous system and may contribute to neuro-inflammation. The CCR5 antagonist maraviroc (MVC) has been suggested to improve HIV-associated neurocognitive impairment (NCI). A double-blind, placebo-controlled, 48-week, randomized study of MVC vs. placebo in people with HIV (PWH) on stable antiretroviral therapy (ART) for more than one year in Hawaii and Puerto Rico with plasma HIV RNA less than 50 copies/ml and at least mild NCI defined as an overall or domain-specific neuropsychological z (NPZ) score less than -0.5. Study participants were randomized 2 : 1 to intensification of ART with MVC vs. placebo. The primary endpoint was change in global and domain-specific NPZ modeled from study entry to week 48. Covariate adjusted treatment comparisons of average changes in cognitive outcome were performed using winsorized NPZ data. Monocyte subset frequencies and chemokine expression as well as plasma biomarker levels were assessed. Forty-nine participants were enrolled with 32 individuals randomized to MVC intensification and 17 to placebo. At baseline, worse NPZ scores were seen in the MVC arm. Comparison of 48-week NPZ change by arm revealed no differences except for a modest improvement in the Learning and Memory domain in the MVC arm, which did not survive multiplicity correction. No significant changes between arms were seen in immunologic parameters. This randomized controlled study found no definitive evidence in favor of MVC intensification among PWH with mild cognitive difficulties. Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

Citation

Cecilia M Shikuma, Valerie Wojna, Victor De Gruttola, Chathura Siriwardhana, Scott A Souza, Rosa J Rodriguez-Benitez, Emilee H Turner, Kalpana Kallianpur, Jacob Bolzenius, Dominic Chow, Miriam Matos, Bruce Shiramizu, Danielle M Clements, Thomas A Premeaux, Lishomwa C Ndhlovu, Robert Paul. Impact of antiretroviral therapy intensification with C-C motif chemokine receptor 5 antagonist maraviroc on HIV-associated neurocognitive impairment. AIDS (London, England). 2023 Nov 01;37(13):1987-1995