Recombinant HIV-1 RT Fragment (M:CRF11 BA17)

Background: There are limited data on the outcomes of acute myocardial infarction-cardiogenic shock (AMI-CS) in patients with HIV infection and AIDS. Setting: Twenty percent sample of all US hospitals. Methods: A retrospective cohort of AMI-CS during 2000-2017 from the National Inpatient Sample was evaluated for concomitant HIV and AIDS. Outcomes of interest included in-hospital mortality and use of cardiac procedures. A subgroup analysis was performed for those with and without AIDS within the HIV cohort. Results: A total 557,974 AMI-CS admissions were included, with HIV and AIDS in 1321 (0.2%) and 985 (0.2%), respectively. The HIV cohort was younger (54.1 vs. 69.0 years), more often men, of non-White race, uninsured, from a lower socioeconomic status, and with higher comorbidity (all P < 0.001). The HIV cohort had comparable multiorgan failure (37.8% vs. 39.0%) and cardiac arrest (28.7% vs. 27.4%) (P > 0.05). The cohorts with and without HIV had comparable rates of coronary angiography (70.2% vs. 69.0%; P = 0.37) but less frequent early coronary angiography (hospital day zero) (39.1% vs. 42.5%; P < 0.001). The cohort with HIV had higher unadjusted but comparable adjusted in-hospital mortality compared with those without [26.9% vs. 37.4%; adjusted odds ratio 1.04 (95% confidence interval: 0.90 to 1.21); P = 0.61]. In the HIV cohort, AIDS was associated with higher in-hospital mortality [28.8% vs. 21.1%; adjusted odds ratio 4.12 (95% confidence interval: 1.89 to 9.00); P < 0.001]. Conclusions: The cohort with HIV had comparable rates of cardiac procedures and in-hospital mortality; however, those with AIDS had higher in-hospital mortality.

Objective HIV-associated CNS dysfunction is a significant problem among people with HIV (PWH), who now live longer due to viral suppression from combined anti-retroviral therapy (ART). Over the course of infection, HIV generates toxic viral proteins and induces inflammatory cytokines that have toxic effects on neurons in the CNS. Among these viral proteins, HIV Nef has been found in neurons of postmortem brain specimens from PWH. However, the source of Nef and its impact on neuronal cell homeostasis are still elusive. Methods and results Here, in using a simian immunodeficiency virus (SIV) infected rhesus macaque model of neuroHIV, we find SIV Nef reactivity in the frontal cortex, hippocampus and cerebellum of SIV-infected animals using immunohistochemistry (IHC). Interestingly, SIV-infected macaques treated with ART also showed frequent Nef positive cells in the cerebellum and hippocampus. Using dual quantitative RNAscope and IHC, we observed cells that were positive for Nef, but were not for SIV RNA, suggesting that Nef protein is present in cells that are not actively infected with SIV. Using cell specific markers, we observed Nef protein in microglia/macrophages and astrocytes. Importantly, we also identified a number of NeuN-positive neurons, which are not permissive to SIV infection, but contained Nef protein. Further characterization of Nef-positive neurons showed caspase 3 activation, indicating late stage apoptosis in the CNS neurons. Conclusions Our results suggest that regardless of ART status, Nef is expressed in the brain of SIV infected macaques and may contribute to neurological complications seen in PWH.