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Background Neurocognitive impairment (NCI) is associated with monocyte activation in people with HIV (PWH). Activated monocytes increase glycolysis, reduce oxidative phosphorylation, and accumulate citrate and succinate, tricarboxylic acid (TCA) cycle metabolites that promote inflammation—this metabolic shift may contribute to NCI and slowed gait speed in PWH. Methods Plasma citrate and succinate were assayed by liquid chromatography–mass spectrometry from 957 participants upon entry to a multicenter, prospective cohort of older PWH. Logistic, linear, and mixed-effects linear regression models were used to examine associations between entry/baseline TCA cycle metabolites and cross-sectional and longitudinal NCI, neuropsychological test scores (NPZ-4), and gait speed. Results Median age was 51 (range 40–78) years. Each 1 standard deviation (SD) citrate increment was associated with 1.18 higher odds of prevalent NCI at baseline (P =.03), 0.07 SD lower time-updated NPZ-4 score (P =.01), and 0.02 m/s slower time-updated gait speed (P <.0001). Age accentuated these effects. In the oldest age-quartile, higher citrate was associated with 1.64 higher odds of prevalent NCI, 0.17 SD lower NPZ-4, and 0.04 m/s slower gait speed (P ≤.01 for each). Similar associations were apparent with succinate in the oldest age-quintile, but not with gait speed. In participants without NCI at entry, higher citrate predicted a faster rate of neurocognitive decline. Conclusions Higher plasma citrate and succinate are associated with worse cross-sectional and longitudinal measures of neurocognitive function and gait speed that are age-dependent, supporting the importance of altered bioenergetic metabolism in the pathogenesis of NCI in older PWH. [ABSTRACT FROM AUTHOR]

Background Food insecurity is associated with increased morbidity and mortality in people with human immunodeficiency virus (HIV) on antiretroviral therapy, but its relationship with immune dysregulation, a hallmark of HIV infection and comorbidity, is unknown. Methods In 241 women participating in the Women's Interagency HIV Study, peripheral blood mononuclear cells were characterized by flow cytometry to identify cell subsets, comprising surface markers of activation (%CD38+HLADR+), senescence (%CD57+CD28−), exhaustion (%PD-1+), and co-stimulation (%CD57− CD28+) on CD4+ and CD8+ T cells. Mixed-effects linear regression models were used to assess the relationships of food insecurity with immune outcomes, accounting for repeated measures at ≤3 study visits and adjusting for sociodemographic and clinical factors. Results At the baseline study visit, 71% of participants identified as non-Hispanic Black, 75% were virally suppressed, and 43% experienced food insecurity. Food insecurity was associated with increased activation of CD4+ and CD8+ T cells, increased senescence of CD8+ T cells, and decreased co-stimulation of CD4+ and CD8+ T cells (all P  < .05), adjusting for age, race/ethnicity, income, education, substance use, smoking, HIV viral load, and CD4 count. In stratified analyses, the association of food insecurity with CD4+ T-cell activation was more pronounced in women with uncontrolled HIV (viral load >40 copies/mL and CD4 <500 cells/mm3) but remained statistically significant in those with controlled HIV. Conclusions Food insecurity may contribute to the persistent immune activation and senescence in women with HIV on antiretroviral therapy, independently of HIV control. Reducing food insecurity may be important for decreasing non–AIDS-related disease risk in this population. [ABSTRACT FROM AUTHOR]

Background Alterations in gut microbiota (GMB) and host metabolites have been noted in individuals with HIV. However, it remains unclear whether alterations in GMB and related functional groups contribute to disrupted host metabolite profiles in these individuals. Methods This study included 185 women (128 with longstanding HIV infection, 88% under antiretroviral therapy; and 57 women without HIV from the same geographic location with comparable characteristics). Stool samples were analyzed by 16S rRNA V4 region sequencing, and GMB function was inferred by PICRUSt. Plasma metabolomic profiling was performed using liquid chromatography–tandem mass spectrometry, and 133 metabolites (amino acids, biogenic amines, acylcarnitines, and lipids) were analyzed. Results Four predominant bacterial genera were identified as associated with HIV infection, with higher abundances of Ruminococcus and Oscillospira and lower abundances of Bifidobacterium and Collinsella in women with HIV than in those without. Women with HIV showed a distinct plasma metabolite profile, which featured elevated glycerophospholipid levels compared with those without HIV. Functional analyses also indicated that GMB lipid metabolism was enriched in women with HIV. Ruminococcus and Oscillospira were among the top bacterial genera contributing to the GMB glycerophospholipid metabolism pathway and showed positive correlations with host plasma glycerophospholipid levels. One bacterial functional capacity in the acetate and propionate biosynthesis pathway was identified to be mainly contributed by Bifidobacterium ; this functional capacity was lower in women with HIV than in women without HIV. Conclusions Our integrative analyses identified altered GMB with related functional capacities that might be associated with disrupted plasma metabolite profiles in women with HIV. [ABSTRACT FROM AUTHOR]