Alterations of brain metabolites in adults with HIV: a systematic meta-analysis of MRS studies

Objective. A meta-analysis of proton magnetic resonance
spectroscopy (MRS) studies to investigate alterations in brain metabolites
in people with HIV (PWH), as well as their relationship with combination
antiretroviral therapy (cART) and cognitive impairment. 
Methods. The PubMed database was searched for studies published
from 1997 to 2020. Twenty-seven studies were identified, which included
1255 PWH and 633 controls. Four metabolites (N-acetyl aspartate (NAA),
myo-Inositol (mI), choline (Cho), and glutamatergic
metabolites (Glx) from five brain regions (basal ganglia (BG), frontal
gray and white matter (FGM, FWM), and parietal gray and white matter (PGM,
PWM)) were pooled separately using random-effects meta-analysis.
Results. During early HIV infection, metabolite alterations were
largely limited to the BG, including Cho elevation, a marker of
inflammation. cART led to global mI and Cho normalization (i.e.,
less elevations), but improvement in NAA was negligible. In chronic PWH on
cART, there were consistent NAA reductions across brain regions, along
with Cho and mI elevations in the FWM and BG, and Glx elevations in the
FWM. Cognitive impairment was associated with NAA reduction and to a
lesser degree, mI elevation.  Conclusions. The basal
ganglia is the primary region affected during early infection. cART is
successful in partially controlling neuroinflammation (global mI and
Cho normalization). However, neuronal dysfunction (NAA
reductions) and neuroinflammation (mI and Cho elevations) persist and
contribute to cognitive impairment in chronic PWH. Novel compounds
targeting NAA signal pathways, along with better neuroinflammation
control, may help to reduce cognitive impairment in PWH.