Characterization of Nef expression in different brain regions of SIV-infected macaques
PLOS ONE
Authors: Yarandi, Shadan S.; Robinson, Jake A.; Vakili, Sarah; Donadoni, Martina; Burdo, Tricia H.; Sariyer, Ilker K.
Abstract
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.
Characteristics of women who use hormonal contraceptives and their population-level impacts on HIV infection in a cohort of South African women (2002-2016)
EUROPEAN JOURNAL OF CONTRACEPTION AND REPRODUCTIVE HEALTH CARE
Authors: Wand, Handan; Morris, Natashia; Reddy, Tarylee
Abstract
Purpose Women's choice of contraceptive can have broader implications and may play a significant role in shaping their sexual practices. We aim to identify the characteristics of women who use hormonal injectables and those at high-risk of HIV infection. We also quantify the population-level impact of their shared characteristics on HIV incidence rates. Materials and methods Data from 9948 women who enrolled in six-HIV prevention trials conducted in South Africa (2002-2016) were included. We used logistic and Cox regression models and estimated the population-level impact of the use of injectables on HIV incidence in the multifactorial-model setting. Results Using hormonal injectables were associated with increased risk of HIV infection (adjusted Hazard ratio (aHR):1.51, 95% CI:1.22, 1.86). At the population level less than 20% of the infections were associated with injectable contraceptives among younger women (i.e., less than 35 years of age). Factors including being single/not-cohabiting, using condoms at last sex, partner-related factors, and STI diagnosis were all identified as shared characteristics of women who preferred using hormonal injectables and those at high-risk of HIV infection. At the population level, these factors were associated with more than 50% of the infections among women younger than 35 years of age. Conclusions Our analysis presented evidence for the overlapping characteristics of the women who used hormonal injectables and those at high-risk of HIV infection. These findings reinforce the importance of comprehensive contraceptive counselling to women about the importance of dual protection, such as male condoms and hormonal contraceptives use.