Impact of ART intensification with CCR5 antagonist maraviroc on HIV-associated neurocognitive impairment.

OBJECTIVES: 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).

DESIGN: A double-blind, placebo-controlled, 48-week, randomized study of MVC vs placebo in people living with HIV (PLWH) on stable antiretroviral therapy (ART) > 1 year in Hawaii and Puerto Rico with plasma HIV RNA <50 copies/mL and at least mild NCI defined as an overall or domain-specific neuropsychological (NP) Z score < -0.5.

METHODS: Study participants were randomized 2:1 to intensification of ART with MVC vs placebo. The primary endpoint was change in global and domain-specific NP Z scores (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.

RESULTS: 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.

CONCLUSIONS: This randomized controlled study found no definitive evidence in favor of MCV intensification among PLWH with mild cognitive difficulties.