Smaller limbic structures are associated with greater immunosuppression in over 1000 HIV-infected adults across five continents: Findings from the ENIGMA-HIV Working Group

Abstract

Research in Context:Evidence before this study HIV type-1 infection can be managed with antiretroviral therapy, however neurocognitive impairment persists even in treated HIV+ individuals. Given the challenges associated with standardized cognitive testing, there is a need to identify quantitative markers of central nervous system impairment. A number of neuroimaging studies have reported brain abnormalities in HIV-infected patients; however, prior studies investigating associations between CD4+ T-cell count or HIV viral load and subcortical brain volume report variable effect sizes and regional distributions of effects, limiting the generalizability of the conclusions drawn to date. We have conducted a literature search for reports in English language journals published until June 2019, using the following search terms: HIV AND subcortical AND neuroimaging AND brain AND viral load AND RNA AND CD4. After removing studies that were not applicable, there were 30 studies investigating CD4+ T-cell count and viral load associations with subcortical brain structure. Added value of the studyThe aim of the current study was to investigate structural brain associations with two biomarkers universally used to monitor immune function and treatment response, namely plasma RNA viral load and CD4+ T-cell counts. Prior analyses have been performed in smaller, heterogeneous cohorts, but by combining data across cohorts, we can identify consistent associations between brain volume and indicators of HIV infection across cohorts. The ENIGMA-HIV Working Group was established to identify common neurobiological signatures of the HIVinfected brain by harmonizing data analysis from HIV neuroimaging studies worldwide. The value of this dataset is that it is well-powered and representative of many HIV+ people living in the cART era. Implications of all the available evidenceOur results provide robust evidence that despite demographic and clinical heterogeneity among HIV-infected individuals, brain abnormalities are consistently linked to HIV viral load and immunosuppression. This supports the importance of achieving viral suppression and immune system restoration in maintaining brain health in people living with HIV. The vulnerability of limbic regions, found in this study, extends beyond the classically implicated regions of the basal ganglia; this suggests that these regions remain an important target of cART era HIV research, especially given their heightened vulnerability to age-associated atrophy and neurodegeneration.

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

“…The availability of combination antiretroviral therapy (cART) has now transformed HIV-infection from a possibly fatal diagnosis to a chronic condition, allowing for viral suppression and stable immune function; however, despite inconsistencies in neuroimaging studies, neurological symptoms and consequences persist. This WG has pooled data from 12 independent neuro-HIV studies from Africa, Asia, Australia, Europe, and North America; volume estimates for eight subcortical brain regions were extracted from anatomical MRI from 1044 HIV + adults (age: 22-81 years) to identify associations with plasma markers reflecting immunosuppression (CD4+ T-cell count) or viral load 124 . Across participants, lower current CD4+ count was associated with smaller hippocampal and thalamic volumes.…”