Improved Cognitive Performance and Reduced Monocyte Activation in Virally Suppressed Chronic HIV After Dual CCR2 and CCR5 Antagonism

Journal of Acquired Immune Deficiency Syndromes : JAIDS
Michelle L DʼAntoniCecilia M Shikuma

Abstract

To evaluate changes in neuropsychological (NP) performance and in plasma and cell surface markers of peripheral monocyte activation/migration after treatment with cenicriviroc (CVC), a dual C-C chemokine receptor type 2 (CCR2) and type 5 (CCR5) antagonist, in treatment-experienced, HIV-infected individuals. Single-arm, 24-week, open-label clinical trial. HIV-infected individuals on antiretroviral therapy ≥1 year with plasma HIV RNA ≤50 copies per milliliter and below-normal cognitive performance [defined as age-, sex-, and education-adjusted NP performance (NPZ) <-0.5 in a single cognitive domain or in global performance] were enrolled. Changes over 24 weeks were assessed for global and domain-specific NPZ scores, plasma markers of monocyte/macrophage activation [neopterin, soluble (s)CD14, and sCD163] quantified by ELISA, and CCR2 and CCR5 expression on monocytes, and T cells measured by flow cytometry. Seventeen of 20 enrolled participants completed the study. Improvements over 24 weeks were observed in global NPZ [median change (Δ) = 0.24; P = 0.008], and in cognitive domains of attention (Δ0.23; P = 0.011) and working memory (Δ0.44; P = 0.017). Plasma levels of sCD163, sCD14 and neopterin decreased significantly (P's < 0.01...Continue Reading

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Citations

Mar 6, 2019·British Journal of Clinical Pharmacology·Jasmini AlagaratnamAlan Winston
Jan 7, 2020·Expert Opinion on Drug Metabolism & Toxicology·Miao MiaoGuangdi Li
Dec 13, 2019·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Joanna KettlewellBruce Shiramizu
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May 28, 2019·Glia·P Lorenzo BozzelliKathleen A Maguire-Zeiss
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Dec 5, 2020·Brain, Behavior, and Immunity·Deanna NeculaMiou Zhou
Mar 13, 2021·AIDS·Suad KapetanovicUNKNOWN International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network

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