Changes in cerebral function parameters with maraviroc-intensified antiretroviral therapy in treatment naive HIV-positive individuals.

Borja Mora-Peris, George Bouliotis, Kulasegaram Ranjababu, Amanda Clarke, Frank A Post, Mark Nelson, Laura Burgess, Juan Tiraboschi, Saye Khoo, Steve Taylor, Deborah Ashby, Alan Winston

Journal: AIDS (London, England) 2019;32(8):1007-1015

PMID: 29438199

Abstract

BACKGROUND

Maraviroc-intensified antiretroviral therapy (ART) may be associated with cognitive benefits.

METHODS

Therapy-naive, cognitively asymptomatic, HIV-positive individuals were randomly allocated on a 1 : 1 basis to standard ART (Arm1: tenofovir-emtricitabine and atazanavir/ritonavir) or maraviroc intensified ART (Arm2: abacavir-lamivudine and darunavir/ritonavir/maraviroc). Over 48 weeks, detailed assessments of cognitive function tests were undertaken and cerebral metabolites measured using proton magnetic resonance spectroscopy. Our primary endpoint was mean change in cognitive function across treatment arms with factors associated with cognitive function changes also assessed.

RESULTS

Of 60 individuals randomized (30 Arm1 and 30 Arm2), 58 were men and 44 of white ethnicity. Treatment groups had similar disease characteristics including overall mean (SD) baseline CD4 cell count 428 (209) and 414 (229) cells/μl, Arms1 and 2, respectively. At week 48, plasma HIV RNA was less than 50 copies/ml in 55 of 56 of those completing study procedures. Cognitive function improved over 48 weeks [mean change z-score (SD) 0.16 (0.09) Arm1 and 0.25 (0.08) Arm2, P = 0.96 for differences between study arms]. A greater increase in frontal grey matter N-acetyl aspartate/creatine ratio was observed in Arm1 [ratio change of 0.071 (SD 0.16)] versus Arm2 [change -0.097 (SD 0.18), P = 0.009], although this was not associated with changes in cognitive function (P = 0.17).

CONCLUSION

Maraviroc-intensified ART had no demonstrable benefit on cognitive function in individuals initiating ART. Greater improvement in neuronal metabolites (N-acetyl aspartate/creatine) was observed with standard ART. Future work should focus on maraviroc-intensified ART in individuals with cognitive impairment.

Address: Division of Infectious Diseases, Department of Medicine.; Imperial Clinical Trials Unit, School of Public Health, Imperial College London.; St. Thomas' Hospital, London.; Brighton and Sussex University Hospital, Brighton.; King's College Hospital.; Chelsea and Westminster Hospital, London.; Department of Pharmacology, University of Liverpool, Liverpool.; Birmingham Heartlands Hospital, Birmingham, UK.
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