The goal of the active U01 is to examine the interactive effects of heavy alcohol use and HIV-1 infection at the level of gut dysbiosis and permeability, ensuing local and systemic inflammation and its pathogenic role in driving HIV infection and aging-associated neuroinflammation and cognitive dysfunction. This is being accomplished through longitudinal studies that systematically examine the role of alcohol use and HIV-1 infection altered microbiome on HIV pathogenesis and development of neurocognitive dysfunction using 16S rRNA gene sequencing and Whole Genome Shotgun (WGS) metagenomic sequencing analysis. The supplement is within the scope of the active award and extends the parent study by including an additional category of participants relevant to Alzheimer?s disease related dementia (ADRD). Specifically, the proposed work is focused on amnestic mild cognitive impairment (aMCI), an early stage of ADRD. Accordingly, the study will include HIV-infected adults with heavy alcohol use and aMCI. There is supporting evidence from pre-clinical rodent studies and few human studies for the role of gut microbiota and peripheral inflammation in the development or progression of Alzheimer?s disease (AD). Notably, there is a complete lack of comprehensive analysis and characterization of the gut microbial dysbiosis in heavy alcohol using HIV+ individuals with ADRD. By contrasting neurocognitive, neuroimaging, and biospecimen indices between heavy alcohol using HIV+ individuals with aMCI and heavy alcohol using HIV+ individuals without aMCI, we will determine whether microbiome abnormalities contribute to the more severe cognitive disturbances and possible development of ADRD. This will enable us to examine the effects of HIV and heavy alcohol use in individuals with and without aMCI/ADRD. Based on the one-year scope and budgetary limits, this supplemental study will differ from the parent project with respect to the inclusion of aMCI and only a single baseline assessment. These supplemental studies will leverage participant recruitment, validated clinical and demographic data, biospecimen/biomarker collection, and clinical expertise utilize from our ongoing NIH sponsored longitudinal studies at the Universities of Louisville (UofL) and Florida (UF) with the following specific aim: Determine HIV-1 infection- and heavy alcohol use-associated qualitative and quantitative changes in the gut microbiome (dysbiosis) and attendant intestinal permeability, microbial translocation (MT) and peripheral inflammation in adults with Alzheimer?s disease related dementias (ADRD).
The proposed supplemental work is focused on amnestic mild cognitive impairment (aMCI), an early stage of ADRD. Accordingly, the study will include HIV-infected adults with heavy alcohol use and aMCI.
