The immune synapses reveal aberrant functions of CD8 T cells during chronic HIV infection

It is well-established that chronic HIV infection causes persistent low-grade inflammation that induces premature aging of the immune system in HIV patient including senescence of memory and effector CD8 T cells. To uncover the reasons of gradually diminished potency of CD8 T cells from chronically HIV infected people, we have analyzed cellular morphology and dynamics of the synaptic interface followed exposure of peripheral polyclonal CD8 T cells at various differentiation stages to planar lipid bilayers. The above parameters were linked to pattern of degranulation that determines efficiency of CD8 T cells cytolytic response. We found a large fraction of naive T cells from HIV infected people developing mature synapses and demonstrating focused degranulation, a signature of a differentiated T cells. Further differentiation of aberrant naive T cells leads to development of anomalous effector T cells undermining their capacity to control HIV and other viruses that could be contained otherwise.

HIV-Associated Structural and Functional Brain Alterations in Homosexual Males

Purpose:Neuroimaging elucidations have shown structural and functional brain alterations in HIV-infected (HIV+) individuals when compared to HIV-negative (HIV–) controls. However, HIV− groups used in previous studies were not specifically considered for sexual orientation, which also affects the brain structures and functions. The current study aimed to characterize the brain alterations associated with HIV infection while controlling for sexual orientation.Methods:Forty-three HIV+ and 40 HIV– homosexual men (HoM) were recruited and underwent resting-state MRI scanning. Group differences in gray matter volume (GMV) were assessed using a voxel-based morphometry analysis. Brain regions with the altered GMV in the HIV+ HoM group were then taken as regions of interest in a seed-based analysis to identify altered functional connectivity. Furthermore, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity values were compared between the two groups to evaluate the HIV-associated functional abnormalities in local brain regions.Results:HIV+ HoM showed significantly increased GMV in the bilateral parahippocampal gyrus and amygdala, and decreased GMV in the right inferior cerebellum, compared with the HIV– HoM. The brain regions with increased GMV were hyper-connected with the left superior cerebellum, right lingual gyrus, and left precuneus in the HIV+ HoM. Moreover, the ALFF values of the right fusiform gyrus, and left parahippocampal gyrus were increased in the HIV+ HoM. The regional homogeneity values of the right anterior cingulate and paracingulate gyri, and left superior cerebellum were decreased in the HIV+ HoM.Conclusion:When the study population was restricted to HoM, HIV+ individuals exhibited structural alterations in the limbic system and cerebellum, and functional abnormalities in the limbic, cerebellum, and visual network. These findings complement the existing knowledge on the HIV-associated neurocognitive impairment from the previous neuroimaging studies by controlling for the potential confounding factor, sexual orientation. Future studies on brain alternations with the exclusion of related factors like sexual orientation are needed to understand the impact of HIV infection on neurocognitive function more accurately.

Advanced HIV Infection in Treatment Naïve Individuals: Effectiveness and Persistence of Recommended Three-Drug Regimens

Background Approximately 20% of newly diagnosed people with HIV (PWH) in the U.S. have advanced HIV infection, yet literature on current antiretroviral therapy (ART) options is limited. Discontinuation/modification and effectiveness of common regimens were compared among ART-naïve people with advanced HIV infection (CD4 cell count <200 cells/μL). Methods ART-naïve adults with advanced HIV infection initiating bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or a boosted darunavir (bDRV)-, dolutegravir (DTG)- or elvitegravir/cobicistat (EVG/c)-based three-drug regimen between 1JAN2018 and 31JUL2019 in the OPERA cohort were included. The association between regimen and discontinuation or viral suppression (<50 or <200 copies/mL) was assessed using Cox proportional hazards models with inverse probability of treatment weights. Results Overall, 961 PWH were included (416 B/F/TAF, 106 bDRV, 271 DTG, 168 EVG/c); 70% achieved a CD4 cell count ≥200 cells/μL over a 16 months median follow-up. All regimens were associated with a statistically higher likelihood of discontinuation than B/F/TAF (bDRV aHR: 2.65 [95% CI: 1.75, 4.02], DTG: 2.42 [1.75, 3.35], EVG/c: 3.52 [95% CI: 2.44, 5.07]). Compared to B/F/TAF, bDRV initiators were statistically less likely to suppress to <50 copies/mL (0.72 [0.52, 0.99]) and <200 copies/mL (0.55 [0.43, 0.70]); no statistically significant difference was detected with DTG or EVG/c. Conclusions Among people with advanced HIV infection, those initiating B/F/TAF were less likely to discontinue/modify their regimen than those on any other regimen, and more likely to achieve viral suppression compared to those on bDRV but not compared to those on other integrase inhibitors.

Very Low Incidence of HIV-infection and Decreasing Incidence of STI Among PrEP Users in 2020 After Introduction of Health Insurance Coverage in Germany

IntroductionObjectives of this study, as part of a nation-wide HIV pre-exposure prophylaxis (PrEP) evaluation project, were to determine the incidence and prevalence of infections with HIV, Chlamydia, Gonorrhea, Syphilis, Hepatitis A/B/C in persons using PrEP, and to describe the health care funded PrEP use in Germany. Additionally, factors associated with Chlamydia/Gonorrhea and Syphilis infections were assessed.MethodsAnonymous data of PrEP users were collected at HIV-specialty centers from 09/2019-12/2020. Incidence rates were calculated per 100 person years (py). Logistic regression was used to analyze risk factors associated with sexually transmitted infections (STIs).Results4620 PrEP users were included: 99.2% male, median age 38 years (IQR 32-45), PrEP indication 98.6% men who have sex with men (MSM). Duration of PrEP use were 5132 py; median duration 451 days (IQR 357-488).Four HIV infections were diagnosed, incidence rate 0,078/100py (95% CI 0.029-0.208). For two suboptimal adherence was reported and in the third case suboptimal adherence and resistance to emtricitabine was observed. One infection was likely acquired before PrEP start.Incidence rates were 21.6/100py for Chlamydia, 23.7/100py for Gonorrhea, 10.1/100py for Syphilis and 55.4/100py for any STI and decreased significantly. 65.5% of Syphilis, 55.6% of Chlamydia and 50.1% of Gonorrhea cases were detected by screening of asymptomatic individuals. In a multivariable analysis among MSM younger age, PrEP start before health insurance coverage and daily PrEP were associated with greater risk for Chlamydia/Gonorrhea. Symptom triggered testing and a history of STI were associated with a higher risk for Chlamydia/Gonorrhea and Syphilis.ConclusionsWe found that HIV-PrEP is almost exclusively used by MSM in Germany. A very low incidence of HIV-infection and decreasing incidence rates of STIs were found in this cohort of PrEP users. The results were likely influenced by the SARS-CoV-2 pandemic. Rollout of PrEP covered by health insurance should be continued to prevent HIV infections. Increased PrEP availability to people at risk of HIV infection through the elimination of barriers requires further attention. Investigation and monitoring with a longer follow-up would be of value.

A Technology-Based Intervention Among Young Men Who Have Sex With Men and Nonbinary People (The Conectad@s Project): Protocol for A Vanguard Mixed Methods Study

Background In many parts of the world, including Brazil, uptake for biomedical interventions has been insufficient to reverse the HIV epidemic among key populations at high risk for HIV, including men who have sex with men. Young MSM (YMSM), particularly Black YMSM, have high HIV incidence, low viral suppression, and low preexposure prophylaxis (PrEP) uptake and adherence. Therefore, novel approaches to increase the HIV biomedical interventions uptake by YMSM are urgently needed. Objective We describe the Conectad@s Project, which aims to: (1) estimate the prevalence and incidence of HIV and other sexually transmitted infections, the onset of sexual risk behavior, and barriers to biomedical interventions among YMSM aged 18 to 24 years in Rio de Janeiro, Brazil; and (2) conduct a technology-based adherence intervention study to promote a rapid linkage of YMSM to HIV care or prevention, and support and sustain adherence. Methods A cross-sectional survey will be conducted with 400 YMSM recruited using respondent-driven sampling (RDS) adapted for social media-based sampling, preceded by a formative phase. HIV and sexually transmitted infections testing will be conducted, including early HIV infection biomarker detection. Behavioral, partnership, network, and structural measures will be collected through structured questionnaires. All individuals recruited for the survey will have access to HIV risk assessment, antiretroviral therapy (ART), PrEP, prevention counseling, and a technology-based adherence intervention. Those who accept the adherence intervention will receive weekly text messages via a social networking app (WhatsApp) for 24 weeks, with follow-up data collected over 48 weeks. Results The Conectad@s project has been approved by our local institutional review board (#CAAE 26086719.0.0000.4262) in accordance with all applicable regulations. Questionnaires for the RDS survey and intervention were developed and tested in 2020, formative interviews were conducted in January and February 2021 to guide the development of the RDS, and enrollment is planned to begin in early 2022. Conclusions The Conectad@s Project is a vanguard study that, for the first time, will apply digital RDS to sample and recruit YMSM in Brazil and rapidly connect them to ART, PrEP, or prevention counseling through a technology-based adherence intervention. RDS will allow us to estimate HIV prevalence among YMSM and measure HIV infection biomarkers in the context of the onset of risky behavior. The data will lay the groundwork to adapt and implement HIV prevention strategies, identify barriers to the earliest HIV infection diagnosis, immediate ART or PrEP initiation, and detect new clusters of HIV transmission. International Registered Report Identifier (IRRID) DERR1-10.2196/34885