Impact of the COVID-19 Pandemic on the PrEP Cascade at Two Veterans Affairs Healthcare Systems.

Overall, fewer Veterans were eligible for PrEP in 2020, compared to 2019, and 2018 (Maryland Veterans Affairs Health Care System- MVAHCS-: n = 890 (2020), n = 1533 (2019); Washington DC Veterans Affairs Medical Center -DC VAMC- n = 1119 (2020), n = 1716 (2019)). While the proportion of Veterans engaged in PrEP out of those eligible for PrEP increased in 2020 compared to 2019 at both sites (MVAHCS: 5.73% (2020) vs. 3.39% (2019) p-value = 0.006; F = 7.58, and DC VAMC: 15.91% (2020) vs. 9.38% (2019) p-value < 0.001; F = 27.64), the absolute number of Veterans engaged in PrEP remained unchanged (MVAHCS n = 51 (2020) and n = 52 (2019); DC VAMC n = 178 (2020) and n = 161 (2019)). Engagement in PrEP was significantly lower among Black Veterans compared to White Veterans at the DC VAMC across all FY with a widening gap in 2020. Cisgender women were less likely to be engaged in PrEP compared to cisgender men at both sites and throughout all FY with a wider gender gap in 2020. There were no significant differences in retention in PrEP between FY.Anticipated improvements in linkage, engagement, and retention in PrEP in 2020 at the MVAHCS and DC VAMC may not have been seen due to the COVID-19 pandemic. Furthermore, engagement rates in PrEP remained low overall, particularly among Black Veterans and cisgender women. Novel PrEP delivery models are needed to engage these populations in PrEP following the COVID-19 pandemic. Interactive dashboards and tele-PrEP may have played a big role in sustained retention in PrEP at the VHA.

Interferon-free hepatitis C treatment increases a surrogate of atherosclerotic cardiovascular disease risk in Black veterans living with HIV.

Veterans living with HIV (VLWH) and hepatitis C virus (HCV) co-infection have an exacerbated risk of cardiovascular disease (CVD). It is unknown if HCV cure reduces CVD risk in this population. We evaluated changes in low-density lipoprotein (LDL), as a surrogate of CVD risk, 18 months after HCV cure in VLWH. We found significant increases in LDL in VLWH with advanced fibrosis, potentially increasing CVD risk. Lower LDL thresholds to initiate lipid-lowering therapies in VLWH after HCV cure may be warranted.

Origins of lateral hypothalamic afferents associated with N-methyl-d-aspartic acid-elicited eating studied using reverse microdialysis of NMDA and Fluorogold.

Afferent projections to the tuberal lateral hypothalamus (tLH), where excitatory amino acid application is most effective in eliciting feeding, and to the anterior, posterior and medial regions of the hypothalamus were studied using reverse microdialysis of N-methyl-D-aspartic acid (NMDA) and Fluorogold (FG). NMDA at 660 microM delivered for 10 min was effective in stimulating food intake only when administered into the tLH, causing a mean intake of 9.3 g compared to less than 1 g in any other site. Subsequent administration of FG through the dialysis probe retrogradely in labeled neurons in brain structures associated with the feeding response including the frontal cortex, amygdala, nucleus accumbens (NA), preoptic areas, substantia nigra, ventral tegmental area (VTA), parabrachial nucleus, and the nucleus of the solitary tract (NST). Labeling after anterior and posterior LH infusion of FG was similar to that seen after tLH delivery with some apparent differences, whereas FG administration into the medial hypothalamus produced a distinctly different pattern of labeling compared to the other groups. Some of the observed labeling appeared to be almost exclusively associated with the tLH where NMDA elicits feeding. In particular, amygdala, preoptic area and shell of the accumbens labeling was noticeably denser in tLH eaters than in all other groups. These findings are consistent with the role of LH glutamate and NMDA receptors in the regulation of food intake and identify afferents to the region which possibly mediate endogenous LH glutamate's effects on feeding.

Regional differences in feeding and other behaviors elicited by N-methyl-D-aspartic acid in the rodent hypothalamus: a reverse microdialysis mapping study.

Regional differences in the feeding stimulatory actions of hypothalamically delivered N-methyl-D-aspartate (NMDA) were investigated. NMDA (660 microM intraprobe) delivered by reverse microdialysis into the tuberal lateral hypothalamus (tLH) reliably elicited feeding in satiated rats. The average food intake was 8.6 g in 50 min, and during the infusion rats spent 26% of the time eating, compared to less than 1% before NMDA treatment. In contrast, NMDA did not affect feeding when reverse dialyzed into the anterior LH (aLH), posterior LH (pLH) or the medial hypothalamus (MH). NMDA had no apparent behavioral effect in the aLH; in contrast, it significantly decreased the time spent resting/sleeping when infused into each of the other three areas tested. Additionally, in the medial hypothalamus, NMDA infusions increased time spent grooming; while in the pLH only alertness was significantly increased. These data underscore the functional and anatomical heterogeneity of the hypothalamus, and implicate glutamate and NMDA receptors in different portions of the hypothalamus in the control of eating, grooming and arousal.

Developmental expression of OAP-1/Tspan-3, a member of the tetraspanin superfamily.

OSP/claudin-11-associated protein (OAP-1/Tspan-3), originally isolated by yeast two-hybrid screening using OSP/claudin-11 (oligodendrocyte-specific protein) as bait, is a member of the tetraspanin superfamily and OAP-1/Tspan-3, OSP/claudin-11, and beta1 integrin form a protein complex that seems to be involved in oligodendrocyte proliferation and migration. This study investigated the temporal and regional expression, glycosylation status, and tissue distribution of OAP-1/Tspan-3. OAP-1/Tspan-3 mRNA was expressed as a single transcript throughout brain development, with high levels of expression in the germinal zones. OAP-1/Tspan-3 protein contains N-terminal glycosylation sites in extracellular loop 2 and deglycosylation studies indicated a decrease in apparent molecular weight of OAP-1/Tspan-3, consistent with removal of N-glycans. Similar to OSP/claudin-11, OAP-1/Tspan-3 is expressed in all stages of oligodendrocyte development and in the myelin sheath. Unlike OSP/claudin-11, however, it is expressed in all cell types tested in the central nervous system (CNS), including neurons and astrocytes. The association of OAP-1/Tspan-3 with OSP/claudin-11 and beta1 integrin, its subcellular distribution as a cell surface, membrane-spanning glycoprotein, and its widespread distribution supports its potential role in cell migration, proliferation, and interactions between cells and extracellular matrix.