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Interleukin 32 (IL-32) is a potent multi-isoform proinflammatory cytokine, which is upregulated in people with HIV (PWH) and is associated with cardiovascular disease (CVD) risk. However, the impact of IL-32 isoforms on CD4 T-cell cardiotropism, a mechanism potentially contributing to heart inflammation, remains unknown. Here we show that IL-32 isoforms β and γ induce the generation of CCR4+CXCR3+ double positive (DP) memory CD4 T-cell subpopulation expressing the tyrosine kinase receptor c-Met, a phenotype associated with heart-homing of T cells. Our ex vivo studies on PWH show that the frequency of DP CD4 T cells is significantly higher in individuals with, compared to individuals without, subclinical atherosclerosis and that DP cells from antiretroviral-naive and treated individuals are highly enriched with HIV DNA. Together, these data demonstrate that IL-32 isoforms have the potential to induce heart-homing of HIV-infected CD4 T cells, which may further aggravate heart inflammation and CVD in PWH. [ABSTRACT FROM AUTHOR]

The article discusses the potential benefits of statin treatment in preventing and reducing frailty, particularly in people with HIV (PWH) who are at a higher risk of cardiovascular disease (CVD) and accelerated aging. The REPRIEVE study, which focused on PWH without pre-existing CVD, found that treatment with pitavastatin reduced the risk of major adverse cardiovascular events (MACE) compared to a placebo. The study suggests that statins may have a geroprotective effect by targeting senescence, a key factor in age-related conditions. However, it also acknowledges the potential adverse effects of statins and the need for further research on their mechanisms of action. The findings from the REPRIEVE study may lead to earlier initiation of statin therapy in PWH and have implications for geroscience-guided therapeutics. [Extracted from the article]

Background Although cell surface immune checkpoint proteins (ICPs) such as PD-1 expressed on T cells are associated with T-cell exhaustion, HIV disease progression, and AIDS events, they have shown limited utility in predicting non-AIDS morbidity. Given that ICPs also exist in soluble forms and are elevated in ART-treated HIV infection, we tested the hypothesis that soluble ICPs may be predictive of non-AIDS events in adults initiating ART. Methods Utilizing a nested case–control study from the AIDS Clinical Trials Group ALLRT cohort, we measured plasma levels of 15 soluble inhibitory and activating ICPs by Luminex. Participants (134 cases, 292 matched controls) were evaluated pre-ART, a year post-ART, and immediately preceding a non-AIDS event, which included myocardial infarction (MI)/stroke, malignancy, serious bacterial infection, and nonaccidental death. Results Conditional logistic regression analysis determined that higher levels of soluble CD27 were associated with increased risk of non-AIDS events at all time points. Higher levels of CD40 at baseline and pre-event and CD80 at pre-event were associated with increased risk of non-AIDS events. Examining specific non-AIDS events, multiple ICPs were associated with malignancy at baseline and pre-event, whereas only higher CD27 levels were associated with increased risk of MI/stroke at year 1 and pre-event. Conclusions While select soluble ICPs were associated with non-AIDS events, CD27 emerged as a consistent marker irrespective of ART. Our data may offer guidance on new targets for early clinical monitoring in people with HIV who remain at greater risk of specific non-AIDS events. [ABSTRACT FROM AUTHOR]

Our study aimed to understand the independent and combined effects of cocaine dependence and HIV status across aspects of verbal memory. Our sample consisted of a total of 102 individuals: 28 individuals living with HIV and cocaine dependence (HIV+/CD), 28 individuals who are HIV-negative with cocaine dependence (HIV-/CD), 20 individuals living with HIV without cocaine dependence (HIV+/ND), and 26 individuals who are HIV-negative without cocaine dependence (HIV-/ND). We utilized the Hopkins Verbal Learning Test-Revised Version (HVLT-R) to assess components of verbal memory, including encoding, recall, and recognition. A 2 (HIV: Yes/No) × 2 (Cocaine: Yes/No) MANCOVA on Total and Delayed Recall while controlling for premorbid intelligence was conducted. We used a Kruskal-Wallis H test to examine retrieval and recognition. The combination of HIV and cocaine dependence amplified deficits on Total Recall. We found comparably poor performance across Delayed Recall between all three clinical groups. People living with HIV without cocaine dependence demonstrated intact recognition, whereas those with cocaine dependence had poor recognition. HIV and cocaine both impacted verbal memory. However, there are potential subtle differences in the role cocaine versus HIV has on the memory process. People living with HIV without cocaine dependence recognized significantly more words than they could freely recall. In contrast, cocaine dependence impacted recognition in HIV and non-HIV groups. These performance patterns suggest HIV may be associated with retrieval deficits, whereas cocaine dependence may be associated with encoding deficits. Further research assessing these specific components of the memory process will help clarify these potential differences. [ABSTRACT FROM AUTHOR]

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]