No abstract

Background: The HIV associated mortality is decreasing in most countries due to the widespread use of antiretroviral therapy. However, HIV-associated neurocognitive disorder (HAND) remains a problematic issue that lowers the quality of life and increases the public health burden among people living with HIV. The prevalence of HAND varies across studies and selected samples. Therefore, we aimed to quantitatively summarize the pooled prevalence of Frascati-criteria-based HAND and to explore the potential demographic, clinical, and immunological factors.Methods: A comprehensive literature search in PubMed/Medline, Web of Science, Embase, and PsycINFO was performed. A random-effects meta-analysis was conducted using the event rate (ER) for the estimation of the incidence of HAND. Subgroup meta-analyses were used to evaluate between-group differences in categorical variables. Meta-regression with the unrestricted maximum likelihood (ML) method was used to evaluate associations of continuous variables.Results: Eighteen studies whose sample sizes ranged from 206 to 1555 were included in the final analyses. The estimated prevalence of HAND, ANI, MND and HAD were 44.9% (95% CI 37.4–52.7%), 26.2% (95% CI 20.7–32.7%), 8.5% (95% CI 5.6–12.7%), 2.1% (95% CI 1.2–3.7%), respectively. Factors associated with HAND were percent female, current CD4 count, education level and country development level (all ps < 0.05).Conclusion: Longitudinal cohort and multimodal neuroimaging studies are needed to verify the clinical prognosis and the underlying neurocognitive mechanism of HAND. In addition, it is urgently necessary to establish a standardized HAND diagnostic process.

Altered gut microbiota has been identified during psychological stress, which causes severe health issues worldwide. The integrity of the intestinal barrier and blood-brain barrier regulates the process of bacterial translocation and can supply the nervous system with real-time information about the environment. However, the association of gut microbiota with psychological stress remains to be fully interpreted. In this study, we established a psychological stress model using an improved communication box and compared the expression of tight junction proteins in multiple regions of the intestinal (duodenum, jejunum, ileum) and blood-brain (amygdala, hippocampus) barriers between model and control rats. We also conducted fecal microbiota analysis using 16S rRNA gene sequencing. Expression levels of the stress-related indicators adrenocorticotropic hormone, NR3C1,2, and norepinephrine were increased in the model group compared to control group. Psychological stress reduced brain and intestinal levels of tight junction proteins, including claudin5, occludin, α-actin, and ZO-1. Microbiota analysis revealed elevated microbial diversity and fecal proportions of Intestinimonas, Catenisphaera, and Globicatella in the model group. Further analysis indicated a negative correlation of Allisonella and Odoribacter, as well as a positive correlation of norank_f__Peptococcaceae, Clostridium_sensu_stricto_1, and Coprococcus_2, with claudin5, occludin, α-actin, and ZO-1. Our use of a rodent model to explore the association between compromised intestinal and blood-brain barriers and altered fecal microbiota under psychological stress improves our understanding of the gut-brain axis. Here, cues converge to control basic developmental processes in the intestine and brain such as barrier function. This study provides new directions for investigating the pathogenesis of emotional disorders and the formulation of clinical treatment.

Background: Pre-exposure prophylaxis (PrEP) is used as an HIV prevention method by people at substantial risk of HIV infection. This systematic review and meta-analysis evaluates current clinical evidence for use of oral TDF-based PrEP among men who have sex with men.Methods: A comprehensive literature search in PubMed, web of science, Google Scholar and ClinicalTrials.gov was performed. A random-effects meta-analysis was conducted using the event rate (ER) for estimation of the incidence of HIV and grade 3 or 4 adverse events (AE) among PrEP arm and using risk ratio (RR) for comparison of incidence of HIV and grade 3 or 4 AE between PrEP recipients and PrEP non-users. Blood-based adherence levels were also divided into three categories with reference to previous meta-analysis. Subgroup meta-analysis was also performed to evaluate whether blood-based adherence levels moderated the effect of TDF-based PrEP on HIV incidence. Narrative review was used due to inconsistent measurements of risk behavior and drug resistance. This review is registered on the PROSPERO database (CRD42017077965).Results: Fourteen studies were included in the review. Oral TDF-based PrEP significantly reduced HIV incidence with minimum drug resistance and tolerable safety risks (HIV incidence, ER = 1.1%, 95% CI 0.6–2.0%, p < 0.001, RR = 0.244, 95% CI 0.111–0.537, p < 0.001 and grade 3 or 4 AEs, ER = 13.0%, 95% CI 9.9–16.9%, p < 0.001, RR = 1.059, 95% CI 0.824–1.362, p = 0.653). Oral TDF-based PrEP was more effective in reducing HIV incidence with high levels of blood-based PrEP adherence (ER, 0.4%) compared to moderate adherence (2.9%; p < 0.001). Most studies found no association between PrEP use and self-reported sexual behavior.Conclusion: Oral TDF-based PrEP is an effective intervention to prevent against HIV infection among MSM. Well-designed implementation science studies that integrate sociobehavioral and biomedical interventions are needed to identify optimal PrEP delivery models in different populations to translate biomedical efficacy into real-world efficacy.