Maraviroc-intensified combined antiretroviral therapy improves cognition in virally suppressed HIV-associated neurocognitive disorder

Abstract

This pilot study provides feasibility, tolerability, proof-of-concept and preliminary evidence for clinically relevant neurocognitive improvement in cART enhancement with maraviroc in virally suppressed HAND patients. Lack of concomitant brain metabolite and biomarker change may be related to complex dynamics of brain repair.

A pilot study on the effects of probiotic supplementation on neuropsychological performance and microRNA‐29a‐c levels in antiretroviral‐treated HIV‐1‐infected patients

“…The discovery that differential microbial composition is associated with alterations in behavior and cognition has significantly contributed to establish the "microbiota-gut-brain-axis" as an extension of the well-accepted "gut-brain-axis" concept. This concept is used to describe the bidirectional communication between the CNS and intestinal organs (Gates et al, 2016).…”

“…Such results, seem to be aligned with what has emerged from a previously study, in which it has been highlighted that a crucial role in the bidirectional communication of the gut-brain-axis, is covered by the hypothalamic-pituitary adrenal (HPA) axis. As well known, the HPA axis is considered the core stress efferent axis that coordinates the adaptive responses of the organism to stressors of any kind, and also it is a part of the limbic system, a crucial zone of the brain predominantly involved in memory and emotional responses (Carabotti et al, 2015;Gates et al, 2016).…”

Central nervous system-penetrating antiretrovirals impair energetic reserve in striatal nerve terminals

“…7). Interestingly, maraviroc has shown preliminary beneficial effects on cognition in HAND (Gates et al , 2016; Ndhlovu et al , 2014), and clinical trials using maraviroc for HAND are underway (ClinicalTrials.gov Identifiers NCT02159027 and NCT02519777), under the hypothesis that such treatment will be beneficial to neuropsychological/neurocognitive performance. Such studies will help ascertain the true effects of maraviroc on the CNS in HAND.…”

Cognitive Impairment and Persistent CNS Injury in Treated HIV

“…In a recent, small, randomized control trial targeting HIV infected participants with cognitive symptoms despite suppressive cART in both plasma and CSF (n=9; HIV RNA < 50 copies/ml), CCR5 inhibitor (maraviroc) intensification to a backbone cART regimen was associated with medium to large effect sizes, favoring improved global cognitive performance at 6 and 12 months [68]. In another single arm, open-labeled study with maraviroc, cognitive improvement was noted, as was a reduction in intracellular HIV DNA, and decreased CD38+ T-lymphocytes, providing mechanistic links to this improvement [69].…”