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J Acquir Immune Defic Syndr. 2018 Sep 1;79(1):108-116. doi: 10.1097/QAI.0000000000001752.

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

Author information

1
Hawai'i Center for AIDS.
2
Department of Tropical Medicine, Medical Microbiology & Pharmacology, University of Hawai'i, Honolulu, HI.
3
University of Missouri-St. Louis, St-Louis, MO.
4
Allergan, South San Francisco, CA.
5
Department of Neurology, Straub Medical Center, Honolulu, HI.
6
Department of Psychology, University of Hawai'i at Manoa, Honolulu, HI.

Abstract

OBJECTIVE:

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.

SETTING:

Single-arm, 24-week, open-label clinical trial.

METHODS:

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.

RESULTS:

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). CCR2 and CCR5 monocyte expression remained unchanged; however, CCR5 levels on CD4 and CD8 T cells and CCR2 expression on CD4 T cells increased (P's < 0.01).

CONCLUSIONS:

CVC given over 24 weeks was associated with improved NP test performance and decreased plasma markers of monocyte immune activation in virally suppressed, HIV-infected participants. These data potentially link changes in monocyte activation to cognitive performance. Further study of CVC for HIV cognitive impairment in a randomized controlled study is warranted.

PMID:
29781885
PMCID:
PMC6092236
[Available on 2019-09-01]
DOI:
10.1097/QAI.0000000000001752

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