Format

Send to

Choose Destination
AIDS. 2016 Feb 20;30(4):591-600. doi: 10.1097/QAD.0000000000000951.

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

Author information

1
aDepartments of Neurology and HIV Medicine, St Vincent's Hospital and Peter Duncan Neurosciences Unit, St Vincent's Centre for Applied Medical Research bFaculty of Medicine, The University of New South Wales cNeuroscience Research Australia dDepartment of Medical Imaging, St Vincent's Hospital eSchool of Medicine, The University of Notre Dame, Sydney, Australia.

Abstract

OBJECTIVE:

To investigate whether intensification of combined antiretroviral therapy (cART) with the CC chemokine receptor type 5 (CCR5) entry inhibitor maraviroc leads to improvement in global neurocognitive functioning in virally suppressed men with HIV-associated neurocognitive disorder (HAND).

DESIGN:

Prospective, double observer-blinded, open-label pilot randomized-controlled trial. Participants were randomized to remain on their existing cART regimen (control arm; n = 8) or receive maraviroc-intensification (maraviroc arm; n = 9).

METHODS:

Participants completed a five-domain neuropsychological battery at baseline, 6- and 12-month visits. Raw scores were transformed into age-corrected z-scores and averaged into a global z-score. Single voxel (H)-magnetic resonance spectroscopy (MRS) major cerebral metabolite concentrations were collected at baseline and 12 months in the basal ganglia and frontal white matter and quantified using jMRUI. Neuroinflammatory biomarkers cerebrospinal fluid neopterin and β2-microglobulin were also measured.

RESULTS:

Fourteen of the 17 participants completed the study: nine maraviroc arm and five control. We found medium to large effect sizes in favour of improved global neurocognitive performance in the maraviroc arm over time {arm*time interaction: P < 0.05; 6 month: [β=-0.10, standard error (SE)= 0.04, 90% confidence interval (90%CI)= -0.18,.03; P < 0.03] yielding a large effect-size d = 0.77 (90%CI = -0.19,1.71); 12 month: [β=-0.01; SE = 0.05; 90%CI = -0.09, 0.06; P < 0.77] yielding a moderate effect-size d = 0.55 (90%CI = -0.47,1.55)}. No treatment-related changes were detected for H-MRS metabolites or cerebrospinal fluid biomarkers.

CONCLUSION:

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.

PMID:
26825032
DOI:
10.1097/QAD.0000000000000951
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wolters Kluwer
Loading ...
Support Center