Different roles of frontal versus striatal atrophy in HIV-associated neurocognitive disorders

Gray matter (GM) atrophy is frequently detected in persons living with HIV, even in the era of combination antiretroviral therapy (cART), but the specificity of regions affected remains elusive. For instance, which regions are consistently affected in HIV? In addition, atrophy at which regions is frequently associated with neurocognitive impairment in HIV? Resolving these questions can potentially help to establish the possible neural profiles of HIV-associated neurocognitive disorders (HAND) severity, which currently is solely defined by neurobehavioral assessments. Here, we addressed these questions using a novel meta-analysis technique, the colocalization-likelihood estimation (CLE) technique, to quantitatively synthesize the findings of GM atrophy in HIV+ adults. Twenty-one of 386 studies published between 1988 and November 2017 and identified in PubMed were selected, plus four identified in other resources. In the end, 25 studies (1,370 HIV+ adults, 889 HIV- controls) were included in the meta-analysis. This technique revealed that GM atrophy in HIV+ adults was dominated by two distinct but nonexclusive profiles: frontal (including anterior cingulate cortex, [ACC]) atrophy, which was associated withHIV-disease and consistently differentiated HIV+ adults from HIV- controls; and caudate/striatum atrophy, which was associated with neurocognitive impairment. The critical role of caudate/striatum atrophy in neurocognitive impairment was further supported by a separate data analysis, which examined the findings of correlation analyses between GM and neurocognitive performance. These results suggest that the frontal lobe and the striatum play critical but differential roles in HAND. A neural model of HAND severity was proposed with several testable predictions.