Before the antiretroviral therapy (ART) era, people living with HIV (PLWH) experienced complications due to AIDS more so than aging. With ART and the extended lifespan of PLWH, HIV comorbidities also include aging—most likely due to accelerated aging—as well as a cardiovascular, neurocognitive disorders, lung and kidney disease, and malignancies. The broad evidence suggests that HIV with ART is associated with accentuated aging, and that the age-related comorbidities occur earlier, due in part to chronic immune activation, co-infections, and possibly the effects of ART alone. Normally the immune system undergoes alterations of lymphocyte and monocyte populations with aging, that include diminished naïve T- and B-lymphocyte numbers, a reliance on memory lymphocytes, and a skewed production of myeloid cells leading to age-related inflammation, termed “inflamm-aging”. Specifically, absolute numbers and relative proportions of monocytes and monocyte subpopulations are skewed with age along with myeloid mitochondrial dysfunction, resulting in increased accumulation of reactive oxygen species (ROS). Additionally, an increase in biomarkers of myeloid activation (IL-6, sCD14, and sCD163) occurs with chronic HIV infection and with age, and may contribute to immunosenescence. Chronic HIV infection accelerates aging; meanwhile, ART treatment may slow age-related acceleration, but is not sufficient to stop aging or age-related comorbidities. Overall, a better understanding of the mechanisms behind accentuated aging with HIV and the effects of myeloid activation and turnover is needed for future therapies.

Background Persistent immune activation is thought to contribute to heightened atherosclerotic cardiovascular disease (ASCVD) risk among people with HIV (PWH). Methods Participants (≥18 years) with versus without HIV and without history of clinical ASCVD were enrolled. We hypothesized that increased macrophage-specific arterial infiltration would relate to plaque composition and systemic immune activation among PWH. We applied a novel targeted molecular imaging approach [technetium-99  m (99mTc)-tilmanocept single photon emission computed tomography (SPECT)/CT] and comprehensive immune phenotyping. Results Aortic 99mTc-tilmanocept uptake was significantly higher among PWH (N = 20) versus participants without HIV (N = 10) with similar 10-year ASCVD risk (P = 0.02). Among PWH, but not among participants without HIV, non-calcified aortic plaque volume related directly to aortic 99mTc-tilmanocept uptake at different uptake thresholds. An interaction (P = 0.001) was seen between HIV status and non-calcified plaque volume, but not calcified plaque (P = 0.83). Systemic levels of caspase-1 (P = 0.004), CD14˗CD16+ (non-classical/patrolling/homing) monocytes (P = 0.0004) and CD8+ T-cells (P = 0.005) related positively and CD4+/CD8 + T-cell ratio (P = 0.02) inversely to aortic 99mTc-tilmanocept uptake volume. Conclusions Macrophage-specific arterial infiltration was higher among PWH and related to non-calcified aortic plaque volume only among PWH. Key systemic markers of immune activation relating to macrophage-specific arterial infiltration may contribute to heightened ASCVD risk among PWH.

Xenotransplantation is considered a potential alternative to allotransplantation to relieve the current shortage of human organs. Due to their similar size and physiology, the organs of pigs are of particular interest for this purpose. Endogenous retroviruses are a result of integration of retroviral genomes into the genome of infected germ cells as DNA proviruses, which are then carried in all cells of the offspring of the organism. Porcine endogenous retroviruses (PERVs) are of special concern because they are found in pig organs and tissues that might otherwise be used for xenotransplantation. PERV proviruses can be induced to replicate and recombine in pigs, and have been shown to infect human cells in vitro. There are three subtypes of PERVs based on differences in the receptor binding domain of the env protein; PERV-A, PERV-B, and PERV-C. PERVs A and B can infect human cells in vitro and can recombine with PERV-C, resulting in a recombinant virus with a higher rate of replication in pig and human cell lines. In this study, we used a PCR-based analysis of 50 domestic and 35 feral pigs to study the distribution of PERVs A, B, and C in swine raised under domestic conditions, versus feral swine from rural areas. PERV-A and PERV-B were universal in both domestic and feral swine. Feral swine had a higher incidence of PERV-C (85.7%) compared to domestic swine (42.0%). Further studies in other feral swine herds are ongoing to verify this observation.

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