Alcohol Use Is Associated with Intestinal Dysbiosis and Dysfunctional CD8+T-Cell Phenotypes in Persons with Human Immunodeficiency Virus

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Journal of Infectious Diseases


Background: Inflammation persists among persons with human immunodeficiency virus (PWH) despite effective antiretroviral therapy and may contribute to T-cell dysfunction. Alcohol use is prevalent among PWH and promotes intestinal leak, dysbiosis, and a proinflammatory milieu. Whether alcohol use is associated with T-cell late differentiation remains to be investigated. Methods: Data and samples from PWH (Nâ...=â...359 of 365) enrolled in the New Orleans Alcohol Use in HIV Study were used. Alcohol use was assessed by self-report (Alcohol Use Disorders Identification Test; lifetime alcohol exposure; 30-day Alcohol Timeline Followback) and phosphatidylethanol (PEth) quantitation. In a subset of participants, fecal bacterial content was assessed by ribosomal 16S marker gene deep sequencing and quantitative polymerase chain reaction. Intestinal leak was assessed by fecal-to-plasma α-1-antitrypsin (A1AT) enzyme-linked immunosorbent assay ratio. Peripheral T-cell populations were quantified by flow cytometry. Results: Alcohol Use Disorder Identification Test scores were positively associated with activated-senescent, exhausted, and terminal effector memory CD45RA+CD8+ but not CD4+ T cells (cells/μL) after confounder adjustment (Pâ...<â....050). Phosphatidylethanol was positively associated with A1AT (Pâ...<â....050). The PEth and activated-senescent CD8+ were associated with bacterial β-diversity (Pâ...<â....050) and positively associated with the relative abundance of coabundant Prevotellaceae members (qâ...<â....100). Conclusions: Alcohol use among PWH is associated with CD8+ T-cell late differentiation, intestinal leak, and dysbiosis. Alcohol-associated dysbiosis is implicated in CD8+ T-cell senescence.

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