Alcohol-associated intestinal dysbiosis in people living with HIV was found to be associated with higher levels of CD8+ T-cell senescence, according to study results published in The Journal of Infectious Diseases.

In post-hoc analyses, researchers analyzed alcohol use data and whole-blood samples from 359 participants in the New Orleans Alcohol Use in HIV study to explore the association between intestinal leak, dysbiosis, and T cells. The subset was composed primarily of virally suppressed, middle-aged African American men (n=251, 51% men who have sex with men) who exhibited relatively high adherence to antiretroviral therapy (ART).

The researchers tested a base and an extended set of covariates to assess the influence of confounding variables. In the base model, adjustments were made for chronological age, body mass index, self-reported sex, African American race, male-male sexual preference, ART adherence >90% of doses, detectable HIV viral load (>20 copies/mL), hepatitis C coinfection, and antibiotic use in the preceding 4 months. Extended models adjusted for the base model covariates plus current smoke-tobacco use, pack-years, days of substance use in the past month, and total years of substance use. In extended models where alcohol variables were not predictors of interest, the 30-day alcohol timeline followback and lifetime alcohol exposure variables were added as potential confounders.

Increasing risk for an alcohol use disorder, as measured by the Alcohol Use Disorders Identification Test (AUDIT), was positively associated with effect on CD8+ T cells but not CD4+ T cells. There were higher levels of activated-senescent CD8+ T cells in the extended covariate model (β=0.014; P =.015). In addition, AUDIT scores were positively associated with exhausted and terminal effector memory cells re-expressing CD45RA CD8+ T cells in the base (β=0.026; P =.001 and β=0.011; P =.014, respectively) and extended models (β=0.034; P <.001 and β=0.012; P =.013, respectively).


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Increasing lifetime alcohol exposure was associated with greater exhausted CD8+ T-cell levels in the extended model (β=0.010; P <.001) suggesting “a potential role for accumulated alcohol exposure in pathological changes to the CD8+ T-cell compartment,” noted the researchers.

Recent alcohol use as measured by the 30-day alcohol timeline followback failed to associate with any CD8+ T-cell population in contrast to phosphatidylethanol (PEth) quantitation. PEth was positively associated with activated-senescent and exhausted CD8+ T cells in the base (β=0.047; P =.010 and β=0.084; P =.005, respectively) and extended (β=0.039; P =.034 and β=0.061; P =.042, respectively) models.  In addition, PEth was positively associated with the α-1-antitrypsin fecal:plasma ratio in the base and extended models (β=0.035; P =.016 and β=0.039; P =.012, respectively), suggesting that intestinal barrier compromise may accompany recent alcohol use.

Both PEth and activated-senescent CD8+ T-cell levels were significantly associated with fecal bacterial β-diversity after covariate adjustment, including men who have sex with men status, and were positively associated with the relative abundance of co-abundant Prevotellaceae members. “Whether products of Prevotella metabolism exert a deleterious effect (i.e. senescence induction) on CD8+ T-cells remains to be tested,” stated the researchers. They added, “The exploratory mediation analyses performed herein offer some evidence in support of a model whereby alcohol-associated relative expansion in intestinal Prevotella exacerbates peripheral CD8+ T-cell senescence.”

Further research is needed to determine whether targeted reversal of alcohol-associated dysbiosis would restore CD8+ T-cell homeostasis.

Reference

Maffei VJ, Siggins RW, Luo M, et al. Alcohol use is associated with intestinal dysbiosis and dysfunctional CD8+ T-cell phenotypes in persons with HIV.  J Infect Dis. Published online July 29, 2020. doi:10.1093/infdis/jiaa461