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Increased risk of false positive HIV ELISA results after COVID-19.

From the first-generation options available in 1985, tests to detect HIV-1 specific antibodies have increased its sensitivity and specificity. HIV-1 and SARS-CoV-2 surface glycoproteins present a certain degree of homology and shared epitope motifs which results of relevance as both pandemics co-exist. Here, we aimed to evaluate the rate of false positive HIV serology results among individuals with COVID-19 diagnosis and in vaccinated subjects. Retrospective analysis of the samples stored at the Infectious Disease Biobank in Argentina from donors with previous COVID-19 diagnosis or anti-SARS-CoV-2 vaccination. Plasma samples were analyzed using Genscreen Ultra HIV Ag-Ab. In those with positive result, the following assays were also performed ELISA lateral flow Determine Early Detect RecomLine HIV-1 HIV-2 IgG and Abbott m2000 RealTime PCR for HIV-1 viral load quantification. In all samples, the presence of anti-SARS-CoV-2 IgG antibodies was evaluated by ELISA using the COVIDAR kit. Statistical analysis was done using Pearson and Fisher exact chi-square test Mann-Whitney and Kruskal-Wallis tests. Globally, the false positive HIV ELISA rate was 1.3% (95% CI 0.66-2.22 chi2 4.68, p 0.03, when compared to the expected 0.4% false positive rate). It increased to 1.4% (95% CI 0.70-2.24, chi2 5.16, p 0.02) when only samples from individuals with previous COVID-19 diagnosis, and to 1.8% (95% CI 0.91-3.06, chi2 7.99, p 0.005) when only individuals with detectable IgG SARS-CoV-2 antibodies were considered. This higher occurrence of HIV false-positive results among individuals with detectable antibodies against Spike SARS-CoV-2 protein should be dispersed among virology testing settings, health providers, authorities.

Hypertensive disorders of pregnancy and HIV analysis of a province-wide cohort during 2018 and 2019.

We evaluated the prevalence of de novo hypertensive disorders of pregnancy (dnHDP) in pregnant people with HIV (PPHIV) in the Western Cape Province, South Africa in 2018-2019 by HIV and antiretroviral therapy (ART) status. All people with a pregnancy outcome from 01012018-31122019 in the Western Cape Provincial Health Data Centre (WCPHDC) were included. The WCPHDC integrates data from multiple electronic platforms according to unique identifiers. dnHDP was classified by ICD-10 code or first-time prescription of antihypertensive drugs <140 days before delivery. Pregnant people with pre-existing hypertension without superimposed pre-eclampsiaeclampsia were not considered to have dnHDP. Adjusted prevalence ratios (aPR) for dnHDP by HIVART status were calculated using Poisson regression with robust variance. Among 180,553 pregnant people studied, 13,677 (7.6%) had dnHDP and 33,978 (18.8%) were PPHIV. Among PPHIV, 11.3% (N 3,827) had no evidence of ART, 59.7% (N 20,283) initiated ART preconception and 29.0% (N 9,868) had ART initiated during pregnancy. Compared to those without HIV (7.7%), dnHDP prevalence was lower in PPHIV with preconception (6.9% aPR 0.78 95% CI 0.74-0.83) or pregnancy-initiated ART (7.0% aPR 0.83 95% CI 0.75-0.92) and higher in PPHIV without ART (9.8% aPR 1.17 95% CI 1.06-1.29) adjusted for maternal age, multiparity, multi-gestation pregnancy and pre-existing hypertension. ART duration by delivery of ≥100 weeks versus pregnancy-initiated ART of 20-<40 weeks was protective (aPR 0.88 95% CI 0.78-0.98). In the context of universal ART, these findings are reassuring for most PPHIV. ART was not associated with increased dnHDP prevalence and longer ART duration was protective.

Role of myeloid cells in system-level immunometabolic dysregulation during prolonged successful HIV-1 treatment.

Why people living with HIV-1 on ART (PLWH ART ) display convoluted metabolism and immune cell functions during prolonged suppressive therapy is not well evaluated. In this study, we aimed to address this question using multiomics methodologies to investigate immunological and metabolic differences between PLWH ART and HIV-1 negative individuals (HC). Cross-sectional study. Untargeted and targeted metabolomics was performed using gas and liquid chromatographymass spectrometry, and targeted proteomics using Olink TM inflammation panel on plasma samples. The cellular metabolic state was further investigated using flow cytometry and intracellular metabolic measurement in single-cell populations isolated by EasySep cell isolation. Finally, flow cytometry was performed for deep-immunophenotyping of mononuclear phagocytes. We detected increased levels of glutamate, lactate, and pyruvate by plasma metabolomics and increased inflammatory markers (e.g., CCL20 and CCL7) in PLWH ART compared to HC. The metabolite transporter detection by flow cytometry in T-cells and monocytes indicated an increased expression of glucose transporter 1 (Glut1) and monocarboxylate transporter 1 (MCT-1) in PLWH ART . Single cell-type metabolite measurement identified decreased glucose, glutamate, and lactate in monocytic cell populations in PLWH ART . Deep-immunophenotyping of myeloid cell lineages subpopulations showed no difference in cell frequency, but expression levels of CCR5 were increased on classical monocytes and some dendritic cells. Our data thus suggest that the myeloid cell populations potentially contribute significantly to the modulated metabolic environment during suppressive HIV-1 Infection.

An estimate of excess deaths among people with HIV during the COVID-19 pandemic in the United States, 2020.

We developed an ad hoc method to estimate the number of excess deaths among persons with HIV (PWH) during the COVID-19 pandemic in the United States. Using this method, we estimated approximately 1,448 excess deaths from COVID-19 among PWH in 2020 in the United States. We also developed an Excel workbook for use as a tool to quickly assess excess deaths among PWH in settings with limited surveillance data.

Longitudinal characterization of circulating extracellular vesicles and small RNA during simian immunodeficiency virus infection and antiretroviral therapy.

Latent infection by human immunodeficiency virus (HIV) hinders viral eradication despite effective antiretroviral treatment (ART). Amongst proposed contributors to viral latency are cellular small RNAs that have also been proposed to shuttle between cells in extracellular vesicles (EVs). Thus, we profiled EV small RNAs during different infection phases to understand the potential relationship between these EV-associated small RNAs and viral infection. A well characterized simian immunodeficiency virus (SIV)macaque model of HIV was used to profile EV-enriched blood plasma fractions harvested during pre-infection, acute infection, latent infectionART treatment, and rebound after ART interruption. Measurement of EV concentration, size distribution, and morphology was complemented with qPCR array for small RNA expression, followed by individual qPCR validations. Iodixanol density gradients were used to separate EV subtypes and virions. Plasma EV particle counts correlated with viral load and peaked during acute infection. However, SIV gag RNA detection showed that virions did not fully explain this peak. EV microRNAs miR-181a, miR-342-3p, and miR-29a decreased with SIV infection and remained downregulated in latency. Interestingly, small nuclear RNA U6 had a tight association with viral load peak. This study is the first to monitor how EV concentration and EV small RNA expression change dynamically in acute viral infection, latency, and rebound in a carefully controlled animal model. These changes may also reveal regulatory roles in retroviral infection and latency.

Experiences of psilocybin treatment for clinical conditions A qualitative meta-synthesis.

There is increasing clinical interest in the use of psilocybin. There is emerging evidence of the efficacy of psilocybin for the treatment of a range of clinical conditions. Mental health nurses have a unique set of skills for caring for people who are hallucinating. To expand these skills to meet the developing clinical interest in the therapeutic use of psilocybin, it is helpful to understand the experience from the perspective of the person being treated with psilocybin. A qualitative meta-synthesis was conducted to examine how those with psilocybin described their experiences to identify whether its effects are similar across different health conditions. Ten studies were included in the review. The health conditions studied were cancer, depression, HIV, substance use disorder, smoking cessation and trauma. The synthesis of findings identified three themes that were common across the studies despite the health condition acceptance, connection and transformation. The review provides helpful insights into how people experience psilocybin and its effects on their health condition.

Demographic Characteristics and Hot-Spot Areas of Recent Infections Among New HIV Diagnoses in Sichuan, China, Between 2018 and 2020.

Sichuan Province is severely affected by the HIV epidemic in China. Little is known about the characteristics of recent infections among new HIV diagnoses, which is critical to prevention strategies, evaluation of the HIV epidemic and health resource allocation. Meanwhile, individuals at primary stages of infection are related to the hot-spot areas of ongoing transmission in new HIV diagnoses, which is also rarely known. This article aimed to report the proportion of recent infections among new HIV diagnoses, and to reveal demographic characteristics associated with HIV recent infections, and finally, to indicate the hot-spot areas of ongoing transmission in Sichuan province between 2018 and 2020. Limiting Antigen (LAg)-Avidity assay was performed to detect recent infection within new HIV diagnoses reported in odd months between 2018 and 2020. Results were reclassified according to the data on CD4 cell count, antiretroviral treatment and the existence of an AIDS-defining illness. Logistic regression was used to determine characteristics associated with HIV recent infections. The spatial analysis was conducted with ArcGIS 10.7 to figure hot-spot areas of HIV recent infections. 42,089 newly diagnosed HIV-1 cases were tested using the LAg-Avidity EIA. In total, 5848 (13.89%) of those were classified as HIV recent infections. Female, age between 18-25 years and men who had sex with men were related to higher proportion of HIV recent infections. Logistic regression revealed that MSM aged between 18-25 years were more likely to be classified as recent infection. Spatial analysis demonstrated significant clustering in Chengdu, Yibin, Luzhou city between 2018 and 2020. Hot spots were mainly clustered in the center of Sichuan in 2018, but gradually spread to southwest and northwest between 2019 and 2020. Enhanced preventive measures among relevant risk groups and areas where the potential HIV-1 transmission is ongoing is urgently needed to curb further spread.

Novel TLR78 agonists promote activation of HIV-1 latent reservoirs and human T and NK cells.

Antiretroviral therapy can successfully suppress HIV-1 replication to undetectable levels but fails to eliminate latent and persistent HIV-1 reservoirs. Recent studies have focused on the immunomodulatory agents such as Toll-like receptor 7 and 8 (TLR7 and TLR8) capable of activating, thereby rendering the reservoir susceptible to antiretroviral inhibition and immune recognition and elimination. In this context, this study focused on generating a diverse repertoire of TLR78 agonists to identify more potent candidates for activating latent HIV-1 and immune cells response. Through combinational strategies of computer-aided design and biological characterization, 159 pyrido 3,2-d pyrimidine and pyridine-2-amine-based derivatives were synthesized. Of which, two TLR78 dual and one TLR8-specific agonists with exceptionally high potency in activating HIV-1 latent reservoirs in cell lines and PBMCs of patients with persistent and durable virologic controls were identified. Particularly, these agonists appeared to enhance NK and T cells activity, which were correlated with the degree of surface activation markers. The outcome of this study highlights the remarkable potential of TLR78 agonists in simultaneously activating HIV-1 from the latently infected cells and augmenting immune effector cells.

Prevalence of HDV infection in people living with HIV Data from a multicenter Italian cohort.

The development of novel antiviral agents active against Hepatitis Delta Virus (HDV) might change the natural history of chronic infection, reducing the risk for end-stage liver disease. People living with HIV (PWH) are at risk for bloodborne pathogens infection, but limited data on epidemiology of HDV infection is available in this setting. The aim of this study was to investigate HDV prevalence and attitude toward HDV testing and treatment in infectious diseases centers. A cross sectional survey was performed among centers participating in the CISAI (Coordinamento Italiano per lo Studio dellAllergia in Infezione da HIV) Group. The survey addressed anti-HDV prevalence and HDV-RNA detectability rates in PWH as well as perceived obstacles to treatment. Overall, responses from ten sites were collected. Among participating centers, 316 PWH with HBV chronic infection are currently followed. Of them, 15.2% had positive anti-HDV antibodies, while 13.9% were not tested yet. Overall, 17% of anti-HDV positive PWH tested at least once for HDV-RNA had active HDV infection, and 71% of them had advanced liver disease. Most infectious diseases centers intend to treat locally HDV infection with upcoming anti-HDV drugs, but some concerns exist regarding treatment schedule. HDV testing needs to be implemented in PWH. At present, few patients followed in the CISAI centers seem to be candidate to receive new direct active anti-HDV agents, but repeated HDV-RNA measures could change this proportion.

The burden of Hepatitis B virus infection in Kenya A systematic review and meta-analysis.

Chronic Hepatitis B virus (HBV) infection causes liver cirrhosis and cancer and is a major public health concern in Kenya. However, so far no systematic review and meta-analysis has been conducted to estimate the burden of disease in the country. A better understanding of HBV infection prevalence will help the government implement efficient strategies at eliminating the disease. This systematic review and meta-analysis was therefore conducted to summarize and update the available information on the burden of HBV in Kenya. We systematically searched PubMed, Science Direct, Web of Science, Scopus, African Journals OnLine, and Google Scholar databases to retrieve primary studies conducted between January 1990 and June 2021 that assessed the prevalence of HBV infection in Kenya based on measurement of the Hepatitis B Surface Antigen (HBsAg). Meta-analysis was performed using the random effects model where HBsAg prevalence was estimated at a 95% confidence interval (CI) after simple pooling analysis. Potential sources of heterogeneity were also investigated. Fifty studies were included in the meta-analysis with a sample size of 108448. The overall pooled prevalence estimate of HBV in Kenya was 7.8% (95% CI 5.8-10.1). Subgroup analysis revealed the highest prevalence among patients presenting with jaundice at 41.7% (95% CI 13.5-73.3) whereas blood donors had the lowest prevalence at 4.1% (95% CI 2.4-6.3). Prevalence in Human Immunodeficiency Virus (HIV)-infected individuals was 8.2% (95% CI 5.8-11.0). An estimate of the total variation between studies revealed substantial heterogeneity (I We present the first systematic review and meta-analysis of the prevalence of HBV in Kenya. Our results show that the burden of HBV in Kenya is still enormous. This calls for an urgent need to implement public health intervention measures and strategic policies that will bring the disease under control and lead to final elimination. httpswww.crd.york.ac.ukprosperodisplayrecord.phpRecordID264859, identifier CRD42021264859.

Does engagement in HIV care affect screening, diagnosis, and control of noncommunicable diseases in sub-Saharan Africa A systematic review and meta-analysis.

Low- and middle-income countries are facing a growing burden of noncommunicable diseases (NCDs). Providing HIV treatment may also provide opportunities to increase access to NCD services in under- resourced environments. We sought to investigate whether reported use of antiretroviral therapy (ART) was associated with increased screening, diagnosis, treatment, andor control of diabetes, hypertension, chronic kidney disease, or cardiovascular disease among people living with HIV (PLWH) in sub-Saharan Africa (SSA). Systematic review and meta-analysis. We searched 10 electronic literature databases for studies published between 01 January 2011 and 31 December 2021 using a comprehensive search strategy. We sought studies reporting on screening, diagnosis, treatment, andor control of NCDs of interest by ART use among non-pregnant adults with HIV >16 years of age in SSA. Random effects models were used to calculate summary odds ratios (ORs) of the risk of diagnosis by ART status and corresponding 95% confidence intervals (95% CIs), where appropriate. Twenty-five studies, describing 13,170 PLWH in SSA, 68% of whom were receiving ART, were included. ART use was associated with a small but imprecise increase in the odds of diabetes diagnosis (OR 1.07 95% CI 0.71, 1.60) and an increase in the odds of hypertension diagnosis (OR 2.10, 95% CI 1.42, 3.09). We found minimal data on the association between ART use and screening, treatment, or control of NCDs. Despite a potentially higher NCD risk among PLWH and regional efforts to integrate NCD and HIV care, evidence to support effective care integration models is lacking.

Occludin regulates HIV-1 infection by modulation of the interferon stimulated OAS gene family.

HIV-1-associated blood brain barrier (BBB) alterations and neurocognitive disorders are frequent clinical manifestations in HIV-1 infected patients. The BBB is formed by cells of the neurovascular unit (NVU) and sealed together by tight junction (TJ) proteins, such as occludin (ocln). Pericytes are a key cell type of NVU that can harbor HIV-1 infection via a mechanism that is regulated, at least in part, by ocln. After viral infection, the immune system starts the production of interferons, which induce the expression of the 2-5-oligoadenylate synthetase (OAS) family of interferon stimulated genes and activate the endoribonuclease RNaseL that provides antiviral protection by viral RNA degradation. The current study evaluated the involvement of the OAS genes in HIV-1 infection of cells of NVU and the role of ocln in controlling OAS antiviral signaling pathway. We identified that ocln modulates the expression levels of the OAS1, OAS2, OAS3, and OASL genes and proteins and, in turn, that the members of the OAS family can influence HIV replication in human brain pericytes. Mechanistically, this effect was regulated via the STAT signaling. HIV-1 infection of pericytes significantly upregulated expression of all OAS genes at the mRNA level but selectively OAS1, OAS2 and OAS3 at the protein level. Interestingly no changes were found in RNaseL after HIV-1 infection. Overall, these results contribute to a better understanding of the molecular mechanisms implicated in the regulation of HIV-1 infection in human brain pericytes and suggest a novel role for ocln in controlling of this process.

SharpNeedlestick Injuries Among Clinical Students at A Tertiary Hospital in Eastern Uganda.

Clinical students, like health workers, are at risk of sharpneedle stick injuries and potential percutaneous exposure to blood and body fluids. They acquire infections like Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) through injuries. This study determined the prevalence and factors associated with sharp injuries among clinical students at Mbale Regional Referral Hospital. Across sectional study was carried out at Mbale Regional Referral Hospital, a teaching hospital located along Pallisa road, Mbale City, Eastern Uganda. Ethical approval was obtained, Printed and soft copy questionnaires eliciting demographics, injury occurrence and associated factors were randomly and conveniently distributed respectively to 322 clinical students. Data was entered in Microsoft excel, cleaned and exported to STATA version 14 for analysis. One hundred sixty (55.2%) clinical students had sustained a sharp injury in their clinical practice with a self-reported prevalence of 46.6% in the last year. The majority of the students 93(68.9%), sustained multiple sharp injuries. The common cause and site of injury were solid needles 72(45%) and finger (83.1%). Most students, 197(67.9%) reported ward procedures not being supervised and 124(42%) students worked on 15 and above patients daily. Final year clinical students were more likely to sustain sharp injuries than semi-finalists (P0.000, OR 3.195% CI 1.7-5.5). Students who worked on ≥15 patients were more likely to sustain a sharp injury than those who attended to < 15 patients daily (P0.000, OR 6.3 95% CI 3.7-10.8%). Students knowledge about sharpinfection control was limited. This study showed a high prevalence of needle stick injuries among clinical students. The associated factors were the year of study, having not learned about infection control, the number of patients attended to daily. Students should attend to a manageable number of patients, carry out procedures not rushing while supervised. It is important to create awareness and train students on infection control before and during their deployment in clinical areas as their health and the future of the health sector depend on them.

Subnational HIV incidence trends in Malawi large, heterogeneous declines across space.

The rate of new HIV infections globally has decreased substantially from its peak in the late 1990s, but the epidemic persists and remains highest in many countries in eastern and southern Africa. Previous research hypothesised that, as the epidemic recedes, it will become increasingly concentrated among sub-populations and geographic areas where transmission is the highest and that are least effectively reached by treatment and prevention services. However, empirical data on subnational HIV incidence trends is sparse, and the local transmission rates in the context of effective treatment scale-up are unknown. In this work, we developed a novel Bayesian spatio-temporal epidemic model to estimate adult HIV prevalence, incidence and treatment coverage at the district level in Malawi from 2010 through the end of 2021. We found that HIV incidence decreased in every district of Malawi between 2010 and 2021 but the rate of decline varied by area. National-level treatment coverage more than tripled between 2010 and 2021 and more than doubled in every district. Large increases in treatment coverage were associated with declines in HIV transmission, with 12 districts having incidence-prevalence ratios of 0.03 or less (a previously suggested threshold for epidemic control). Across districts, incidence varied more than HIV prevalence and ART coverage, suggesting that the epidemic is becoming increasingly spatially concentrated. Our results highlight the success of the Malawi HIV treatment programme over the past decade, with large improvements in treatment coverage leading to commensurate declines in incidence. More broadly, we demonstrate the utility of spatially resolved HIV modelling in generalized epidemic settings. By estimating temporal changes in key epidemic indicators at a relatively fine spatial resolution, we were able to directly assess, for the first time, whether the ART scaleup in Malawi resulted in spatial gaps or hotspots. Regular use of this type of analysis will allow HIV program managers to monitor the equity of their treatment and prevention programmes and their subnational progress towards epidemic control.

Population mobility and the development of Botswanas generalized HIV epidemic a network analysis.

The majority of people with HIV live in sub-Saharan Africa, where HIV epidemics are generalized. For these epidemics to develop, populations need to be mobile. However, population-level mobility has not yet been studied in the context of the development of generalized HIV epidemics. Here we do so by studying historical migration data from Botswana which has one of the most severe generalized HIV epidemics worldwide in 2021, HIV prevalence was 21%. The country reported its first AIDS case in 1985 when it began to rapidly urbanize. We hypothesize that, during the development of Botswanas epidemic, the population was highly mobile and there were substantial urban-to-rural and rural-to-urban migratory flows. We test this hypothesis by conducting a network analysis using a historical time series (1981 to 2011) of micro-census data from Botswana. We found 10% of the population moved their residency annually, complex migration networks connected urban with rural areas, and there were very high rates of rural-to-urban migration. Notably, we also found mining towns were both important in-flow and out-flow migration hubs consequently, there was a very high turnover of residents in towns. Our results support our hypothesis, and together, provide one explanation for the development of Botswanas generalized epidemic.

Automated microarray for single-cell sorting and collection of lymphocytes following HIV reactivation.

A promising strategy to cure HIV infected individuals is to use latency reversing agents (LRAs) to reactivate latent viruses, followed by host clearance of infected reservoir cells. However, reactivation of latent proviruses within infected cells is heterogeneous and often incomplete. This fact limits strategies to cure HIV which may require complete elimination of viable virus from all cellular reservoirs. For this reason, understanding the mechanism(s) of reactivation of HIV within cellular reservoirs is critical to achieve therapeutic success. Methodologies enabling temporal tracking of single cells as they reactivate followed by sorting and molecular analysis of those cells are urgently needed. To this end, microraft arrays were adapted to image T-lymphocytes expressing mCherry under the control of the HIV long terminal repeat (LTR) promoter, in response to the application of various LRAs (prostratin, iBET151, and SAHA). In response to prostratin, iBET151, and SAHA, 30.5 %, 11.2 %, and 12.1 % percentage of cells respectively, reactivated similar to that observed in other experimental systems. The arrays enabled large numbers of single cells (>25,000) to be imaged over time. mCherry fluorescence quantification identified cell subpopulations with differing reactivation kinetics. Significant heterogeneity was observed at the single cell level between different LRAs in terms of time to reactivation, rate of mCherry fluorescence increase upon reactivation, and peak fluorescence attained. In response to prostratin, subpopulations of T lymphocytes with slow and fast reactivation kinetics were identified. Single T-lymphocytes that were either fast or slow reactivators were sorted, and single-cell RNA-sequencing was performed. Different genes associated with inflammation, immune activation, and cellular and viral transcription factors were found. These results advance our conceptual understanding of HIV reactivation dynamics at the single-cell level toward a cure for HIV.

Multiplex analysis of cytokines and chemokines in persons aging with or without HIV.

People with HIV (PWH) on combined antiretroviral therapy (cART) are living longer lives due to modern cART advances and increased routine medical care. The full landscape of aging with HIV is unclear given that HIV emerged relatively recently in human history and initially had a high mortality rate, there has not been a substantially aged population to evaluate. In the present study, we set out to perform high throughput plasma analyte profiling by multiplex analysis, focusing on various T helper (Th)-related cytokines, chemokines, and pro- and anti-inflammatory cytokines. The primary goals being to provide reference ranges of these analytes for aging PWH cohorts, as well as testing the utility of high throughput multiplex plasma assays. The cohort used in this study was comprised of age-matched healthy donors (aged 32.6-73.5), PWH on cART (aged 26.7-60.2), and viremic PWH (aged 27.5-59.4). The patients in each group were then stratified across the age span to examine age-related impacts of these plasma biomarkers. Our results largely indicate feasibility of plasma analyte monitoring by multiplex and demonstrate a high degree of person-to-person variability regardless of age and HIV status. Nonetheless, we find multiple associations with age, duration of known infection, and viral load, all of which appear to be driven by either prolonged HIV disease progression or long-term use of cART.

Optimising the yield from bronchoalveolar lavage on human participants in infectious disease immunology research.

Bronchoalveolar lavage (BAL) is becoming a common procedure for research into infectious disease immunology. Little is known about the clinical factors which influence the main outcomes of the procedure. In research participants who underwent BAL according to guidelines, the BAL volume yield, and cell yield, concentration, viability, pellet colour and differential count were analysed for association with important participant characteristics such as active tuberculosis (TB) disease, TB exposure, HIV infection and recent SARS-CoV-2 infection. In 337 participants, BAL volume and BAL cell count were correlated in those with active TB disease, and current smokers. The right middle lobe yielded the highest volume. BAL cell and volume yields were lower in older participants, who also had more neutrophils. Current smokers yielded lower volumes and higher numbers of all cell types, and usually had a black pellet. Active TB disease was associated with higher cell yields, and higher proportions of granulocytes, but this declined at the end of treatment. HIV infection was associated with lower cell yields and more bloody pellets, and recent SARS-CoV-2 infection with a higher proportion of lymphocytes. These results allow researchers to optimise their participant and end assay selection for projects involving lung immune cells.

Pre-existing autoimmunity is associated with increased severity of COVID-19 A retrospective cohort study using data from the National COVID Cohort Collaborative (N3C).

Identifying individuals with a higher risk of developing severe COVID-19 outcomes will inform targeted or more intensive clinical monitoring and management. To examine, using data from the National COVID Cohort Collaborative (N3C), whether patients with pre-existing autoimmune disease (AID) diagnosis andor immunosuppressant (IS) exposure are at a higher risk of developing severe COVID-19 outcomes. A retrospective cohort of 2,453,799 individuals diagnosed with COVID-19 between January 1 Two outcomes of COVID-19 severity, derived from the World Health Organization severity score, were defined, namely life-threatening disease and hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression models with and without adjustment for demographics (age, BMI, gender, race, ethnicity, smoking status), and comorbidities (cardiovascular disease, dementia, pulmonary disease, liver disease, type 2 diabetes mellitus, kidney disease, cancer, and HIV infection). In total, 2,453,799 (16.11% of the N3C cohort) adults (age> 18 years) were diagnosed with COVID-19, of which 191,520 (7.81%) had a prior AID diagnosis, and 278,095 (11.33%) had a prior IS exposure. Logistic regression models adjusted for demographic factors and comorbidities demonstrated that individuals with a prior AID (OR 1.13, 95% CI 1.09 - 1.17 Patients with pre-existing AID, exposure to IS, or both are more likely to have a life-threatening disease or hospitalization. These patients may thus require tailored monitoring and preventative measures to minimize negative consequences of COVID-19.

A simulation and experiential learning intervention for labor and delivery providers to address HIV stigma during childbirth in Tanzania Study protocol for the evaluation of the MAMA intervention.

Integrating services for HIV and multidrug-resistant tuberculosis A global cross-sectional survey among ART clinics in low- and middle-income countries.

Tuberculosis (TB) is the leading cause of death among PLHIV and multidrug-resistant-TB (MDR-TB) is associated with high mortality. We examined the management for adult PLHIV coinfected with MDR-TB at ART clinics in lower income countries. Between 2019 and 2020, we conducted a cross-sectional survey at 29 ART clinics in high TB burden countries within the global IeDEA network. We used structured questionnaires to collect clinic-level data on the TB and HIV services and the availability of diagnostic tools and treatment for MDR-TB. Of 29 ART clinics, 25 (86%) were in urban areas and 19 (66%) were tertiary care clinics. Integrated HIV-TB services were reported at 25 (86%) ART clinics for pan-susceptible TB, and 14 (48%) clinics reported full MDR-TB services on-site, i.e. drug susceptibility testing DST and MDR-TB treatment. Some form of DST was available on-site at 22 (76%) clinics, while the remainder referred testing off-site. On-site DST for second-line drugs was available at 9 (31%) clinics. MDR-TB treatment was delivered on-site at 15 (52%) clinics, with 10 individualizing treatment based on DST results and five using standardized regimens alone. Bedaquiline was routinely available at 5 (17%) clinics and delamanid at 3 (10%) clinics. Although most ART clinics reported having integrated HIV and TB services, few had fully integrated MDR-TB services. There is a continued need for increased access to diagnostic and treatment options for MDR-TB patients and better integration of MDR-TB services into the HIV care continuum.

Between two pandemics Older, gay mens experiences across HIVAIDS and COVID-19.

Pandemics are a component of human life, and have had great bearing on the trajectory of human evolution. Historically, the biomedical aspects of pandemics have been overrepresented, but there is growing recognition of the degree to which pandemics are socially and culturally embedded, highlighting how virus perception is socially and politically informed. Older (50), gay men represent a population who have experienced two global pandemics in their lifespans HIVAIDS and COVID-19. Although governments and health officials largely failed gay men during the HIVAIDS pandemic, gay men represent an important source of pandemic information and their experiences have much to offer health professionals and policymakers. As such, a small but growing body of literature has compared gay mens experiences amidst the two pandemics. The current study drew on constructivist grounded theory methods to examine how living through the HIVAIDS pandemic has influenced older gay mens perspectives of COVID-19. Twenty Canadian-based gay men aged 50 participated in semi-structured interviews via Zoom. Analysis revealed three key processes (1) uncertainty and the familiarity of loss, (2) witnessing pandemic inequities, and, (3) navigating constantly evolving (mis)information. We highlight the utility of this knowledge to informing future pandemic planning and policies.

Measuring social norms and attitudes about age-disparate transactional sex Psychometric testing of the NAATSS.

Transactional sex between girls under 18 years-old and adult men at least ten years older, known as age-disparate transactional sex (ADTS), is an established risk factor for HIV, STI and early pregnancy among girls and women. Social norms or beliefs about what others expect from you and what others do can sustain behaviours such as ADTS even when individuals may be personally against them. In order to evaluate interventions to change social norms, validated instruments for measuring change in personal beliefs and social norms regarding ADTS are needed. Items for the Factor analysis revealed three factors in each domain. The factors were labelled Attributions to Girls Behaviour which has 5 items, Mens Motivations with 5 items, and Girls Readiness to have Sex with 3 items. The subscales evidenced acceptable reliability with Cronbachs alphas ranging from 0.72 to 0.83 for the social norms subscales and 0.59 to 0.82 for the personal beliefs subscales. The items were developed based on qualitative research and expert rankings and the resulting This work was supported by the OAK Foundation grant number OCAY-16-188.

Effect of Direct Antiviral Therapy Against HCV on CD4 T Cell Count in Patients with HIV-HCV Coinfection.

HCV-related liver disease is an important cause of morbidity and mortality in patients with HIV infection. It is well known that the response rates to HCV therapy are similar between HCV-monoinfected patients and HIV-HV coinfected ones. The aim of this study was to evaluate the impact of HCV eradication on CD4 T cell count in a population of HIV-HCV coinfected patients. We enrolled patients with HIV-HCV coinfection attending the Infectious Diseases Unit of the A.O.U. Federico II of Naples, from January 2016 to February 2019, treated with ART (AntiRetroviral Therapy) and DAAs (Direct Antiviral Agents). For each patient, we evaluated HIV and HCV viral load and CD4 T cell count before starting therapy with DAAs, by SVR12 time and by SVR48 time. Fibrosis was evaluated by the mean of Fibroscan Fifty-two patients were enrolled, 40 males. Fibrosis score was F0-F3 in 15 patients and cirrhosis in the remaining 11 (all in Child-Pugh class A). All had been receiving ART, and all were treated with DAAs. Only patient who had not achieved HIV viral suppression for non-compliance also experienced a relapse of HCV infection after the end of DAAs. In all patients, we observed that the CD4 T cell count at baseline did not show significant variations compared to SVR12 and SVR48 time. We also assessed CD4 count in relation to HIV categories and stage of liver disease, see Table 1. Also, based on the assessments of the subclasses considered, there were no significant changes in the CD4 T cell count. Our study shows that HCV viral eradication obtained with DAAs in patients with HIV-HCV coinfection is not associated with significant changes in the CD4 T cell count, regardless of CDC category and stage of liver disease.

Estimated costs and quality-adjusted life-years lost due to N. gonorrhoeae infections acquired in 2015 in the United States A modelling study of overall burden and disparities by age, raceethnicity, and other factors.

Disparities in the health and economic burden of gonorrhoea have not been systematically quantified. We estimated population-level health losses and costs associated with gonococcal infection and sequelae in the United States We used probability-tree models to capture gonorrhoea sequelae and to estimate attributable disease burden in terms of the discounted lifetime costs and quality-adjusted life-years (QALYs) lost due to incident infections acquired during 2015 from the healthcare system perspective. Numbers of infections in 2015 were obtained from a published gonorrhoea transmission model. We evaluated population-level disease burden, disaggregated by sex, age, raceethnicity, and for men who have sex with men (MSM). We conducted a multivariate sensitivity analysis for key parameters. Discounted lifetime QALYs lost per incident gonococcal infection were estimated as 0.093 (95% uncertainty interval UI 0.022-0.22) for women, 0.0020 (0.0015-0.0024) for heterosexual men, and 0.0015 (0.00070-0.0021) for MSM. Discounted lifetime costs per incident infection were USD 261 (109-480), 169 (88-263), and 133 (50-239), respectively. At the population level, total discounted lifetime QALYs lost due to infections acquired during 2015 were 53,293 (12,326-125,366) for women, 621 (430-872) for heterosexual men, and 1,078 (427-1,870) for MSM. Total discounted lifetime costs were USD 150 million (64-277 million), 54 million (25-92 million), and 97 million (34-197 million), respectively. The highest total burden of both QALYs and costs at the population-level was observed in Non-Hispanic Black women, and highest burden per 1,000 person-years was identified in MSM among men and American IndianAlaska Native among women. Gonorrhoea causes substantial health losses and costs in the United States. These results can inform planning and prioritization of prevention services. Centers for Disease Control and Prevention, Charles A. King Trust.

Engaging Stigmatised Communities in Australia with Digital Health Systems Towards Data Justice in Public Health.

In 2018, following government policy changes to Australias national electronic health record system, My Health Record, consumer advocates-including organisations representing people living with HIV, people who use drugs and sex workers-raised concerns about privacy and data security. Responding to these controversies, this study explores the practical, ethical and political complexities of engaging stigmatised communities with digital health systems. We conducted 16 qualitative semi-structured interviews in 2020 with key informants representing communities who experience stigma, discrimination and marginalisation in Australia. These communities included people living with HIV, sex workers, people who inject drugs, gay and bisexual men and transgender and gender diverse people. We conducted a reflexive thematic analysis. Key informants were sceptical of proposed benefits of electronic health records for their communities, and concerned about privacy risks and the potential for discrimination. Meaningful consultation, consent mechanisms and tackling structural stigma were raised as solutions for engaging communities. Although communities could benefit from being included in digital health systems, significant cultural, legal and social reforms from government were believed to be necessary to build trust in digital health systems. We argue that these forms of data justice are necessary for effective future systems. Engaging stigmatised communities-including in relation to gender, sexuality, sex work, drug use, HIV-requires a commitment to data justice. The design and implementation of digital health systems requires investment in ongoing and meaningful consultation with communities and representative organisations.

The COVID-19, tuberculosis and HIVAIDS Ménage à Trois.

In December 2019, a novel pneumonic condition, Coronavirus disease 2019 (COVID- 19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out in China and spread globally. The presentation of COVID-19 is more severe in persons with underlying medical conditions such as Tuberculosis (TB), Human Immunodeficiency VirusAcquired Immunodeficiency Syndrome (HIVAIDS) and other pneumonic conditions. All three diseases are of global concern and can significantly affect the lungs with characteristic cytokine storm, immunosuppression, and respiratory failure. Co-infections of SARS-CoV-2 with HIV and

Immunoinformatics design of multivalent epitope vaccine against monkeypox virus and its variants using membrane-bound, enveloped, and extracellular proteins as targets.

The current monkeypox (MPX) outbreak, caused by the monkeypox virus (MPXV), has turned into a global concern, with over 59,000 infection cases and 23 deaths worldwide. Herein, we aimed to exploit robust immunoinformatics approach, targeting membrane-bound, enveloped, and extracellular proteins of MPXV to formulate a chimeric antigen. Such a strategy could similarly be applied for identifying immunodominant epitopes and designing multi-epitope vaccine ensembles in other pathogens responsible for chronic pathologies that are difficult to intervene against. A reverse vaccinology pipeline was used to select 11 potential vaccine candidates, which were screened and mapped to predict immunodominant B-cell and T-cell epitopes. The finalized epitopes were merged with the aid of suitable linkers, an adjuvant (Resuscitation-promoting factor), a PADRE sequence (13 aa), and an HIV TAT sequence (11 aa) to formulate a multivalent epitope vaccine. Bioinformatics tools were employed to carry out codon adaptation and computational cloning. The tertiary structure of the chimeric vaccine construct was modeled via I-TASSER, and its interaction with Toll-like receptor 4 (TLR4) was evaluated using molecular docking and molecular dynamics simulation. C-ImmSim server was implemented to examine the immune response against the designed multi-epitope antigen. The designed chimeric vaccine construct included 21 immunodominant epitopes (six B-cell, eight cytotoxic T lymphocyte, and seven helper T-lymphocyte) and is predicted non-allergen, antigenic, soluble, with suitable physicochemical features, that can promote cross-protection among the MPXV strains. The selected epitopes indicated a wide global population coverage (93.62%). Most finalized epitopes have 70%-100% sequence similarity with the experimentally validated immune epitopes of the vaccinia virus, which can be helpful in the speedy progression of vaccine design. Lastly, molecular docking and molecular dynamics simulation computed stable and energetically favourable interaction between the putative antigen and TLR4. Our results show that the multi-epitope vaccine might elicit cellular and humoral immune responses and could be a potential vaccine candidate against the MPXV infection. Further experimental testing of the proposed vaccine is warranted to validate its safety and efficacy profile.

Unequal distribution of genetically-intact HIV-1 proviruses in cells expressing the immune checkpoint markers PD-1 andor CTLA-4.

HIV-1 persists in resting CD4 We obtained peripheral blood from 16 HIV-1-infected participants, and paired lymph node from four of these participants, during effective ART. Memory CD4 In peripheral blood, we observed that proviruses found within PD-1

Otosyphilis.

Otosyphilis can be challenging to diagnose, but, if left unrecognized, it may cause irreversible damage. An immunologic interplay between syphilis and human immunodeficiency virus (HIV) makes coinfection likely and may predispose people with HIV to neurosyphilis. In this study, we present a case of a man in his 50s with hearing loss and vertigo diagnosed with otosyphilis as well as a new diagnosis of HIV. This case and corresponding discussion serve to inform the noninfectious disease-trained clinician of the symptoms, diagnostics, and treatment options for otosyphilis as well as to discuss the relationship between HIV and syphilis and demonstrate the importance of disease recognition.

Nationwide Measles and Rubella Outbreaks in South Sudan, 2019.

South Sudan confirmed a measles outbreak in December 2018. An investigation was conducted to assess underlying causes of the outbreak. Vaccination coverage and measles surveillance data were analyzed. A suspected measles case had fever, maculopapular rash, and cough or conjunctivitis. A confirmed measles case had generalized maculopapular rash lasting >3 days, a temperature >38°C, and cough or conjunctivitis or serologic confirmation (anti-measles immunoglobin M IgM antibody detection) in serum samples collected ≤30 days from rash onset. A confirmed rubella case tested measles IgM-negative and rubella IgM-positive. Nationwide, 3727 suspected measles cases were reported in 2019. Seventy-five percent of all suspected measles cases were in children aged <5 years. Thirty-six percent of patients with suspected measles were admitted to the hospital, and 36 measles-related deaths were reported. Among cases, 922 (25%) were tested for measles of these, 317 (34%) were measles IgM-positive. Among cases that tested measles IgM-negative, 149 (33%) were rubella IgM-positive. Immunization coverage for 1 dose of measles-containing vaccine (MCV) varied by state, ranging from 6% to 67%. Measles and rubella remain public health problems in South Sudan. To reduce measles incidence, South Sudan needs to achieve >95% coverage with 2 doses of MCV.

Homonegative Victimization and Perceived Stress among Adolescent Sexual Minority Males The Attenuating Role of Peer and Family Support.

Research suggests social support may protect sexual minorities from the harmful effects of victimization that undermine mental and sexual health wellness however, this relationship has been underexplored among a diverse youth population. We examined the association between lifetime homonegative victimization, perceived stress in the last month, and resilience factors among a diverse sample of adolescent sexual minority males. Data were collected between June 2018 and April 2020 as part of the MyPEEPS Mobile study, a multi-site randomized controlled trial evaluating the effectiveness of a mobile behavioral HIV prevention intervention for adolescents living in the U.S. We analyzed baseline survey data from 542 sexual minority males, aged 13-18 years. We used bivariate analyses to examine relationships among variables and multivariable linear regression models to determine if resilience factors attenuated the association between homonegative victimization and perceived stress. Perceived stress was positively associated with younger age, internalized homophobia, experiencing verbal victimization, threats of being outed, and threats of physical violence. Relying on online friends for support and having good family relations both attenuated the relationship between verbal victimization and perceived stress. However, neither of these resilience factors significantly weakened the associations between perceived stress, threats of physical violence, and being outed. Resilience factors, including peer and family support, may play an attenuating role in the relationship between homonegative victimization and perceived stress among adolescent sexual minority males.

Ambulatory and hospitalized patients with suspected and confirmed mpox an observational cohort study from Brazil.

By October 30, 2022, 76,871 cases of mpox were reported worldwide, with 20,614 cases in Latin America. This study reports characteristics of a case series of suspected and confirmed mpox cases at a referral infectious diseases center in Rio de Janeiro, Brazil. This was a single-center, prospective, observational cohort study that enrolled all patients with suspected mpox between June 12 and August 19, 2022. Mpox was confirmed by a PCR test. We compared characteristics of confirmed and non-confirmed cases, and among confirmed cases according to HIV status using distribution tests. Kernel estimation was used for exploratory spatial analysis. Of 342 individuals with suspected mpox, 208 (60.8%) were confirmed cases. Compared to non-confirmed cases, confirmed cases were more frequent among individuals aged 30-39 years, cisgender men (96.2% vs. 66.4% p < 0.0001), reporting recent sexual intercourse (95.0% vs. 69.4% p < 0.0001) and using PrEP (31.6% vs. 10.1% p < 0.0001). HIV (53.2% vs. 20.2% p < 0.0001), HCV (9.8% vs. 1.1% p 0.0046), syphilis (21.2% vs. 16.3% p 0.43) and other STIs (33.0% vs. 21.6% p 0.042) were more frequent among confirmed mpox cases. Confirmed cases presented more genital (77.3% vs. 39.8% p < 0.0001) and anal lesions (33.1% vs. 11.5% p < 0.0001), proctitis (37.1% vs. 13.3% p < 0.0001) and systemic signs and symptoms (83.2% vs. 64.5% p 0.0003) than non-confirmed cases. Compared to confirmed mpox HIV-negative, HIV-positive individuals were older, had more HCV coinfection (15.2% vs. 3.7% p 0.011), anal lesions (45.7% vs. 20.5% p < 0.001) and clinical features of proctitis (45.2% vs. 29.3% p 0.058). Mpox transmission in Rio de Janeiro, Brazil, rapidly evolved into a local epidemic, with sexual contact playing a crucial role in its dynamics and high rates of coinfections with other STI. Preventive measures must address stigma and social vulnerabilities. Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (INI-Fiocruz).

Finding and treating early-stage HIV infections A cost-effectiveness analysis of the

We adapted a compartmental model of HIV transmission to evaluate the cost-effectiveness of the The Our analysis suggests that in Lima, Peru the National Institutes of Health.

Clinical value of

HIV is still a major public health problem. At present, HIV-associated lymphoma remains the leading cause of deaths among people living with HIV, which should be paid more attention to.

COMMD proteins function and their regulating roles in tumors.

The COMMD proteins are a highly conserved protein family with ten members that play a crucial role in a variety of biological activities, including copper metabolism, endosomal sorting, ion transport, and other processes. Recent research have demonstrated that the COMMD proteins are closely associated with a wide range of disorders, such as hepatitis, myocardial ischemia, cerebral ischemia, HIV infection, and cancer. Among these, the role of COMMD proteins in tumors has been thoroughly explored they promote or inhibit cancers such as lung cancer, liver cancer, gastric cancer, and prostate cancer. COMMD proteins can influence tumor proliferation, invasion, metastasis, and tumor angiogenesis, which are strongly related to the prognosis of tumors and are possible therapeutic targets for treating tumors. In terms of molecular mechanism, COMMD proteins in tumor cells regulate the oncogenes of NF-κB, HIF, c-MYC, and others, and are related to signaling pathways including apoptosis, autophagy, and ferroptosis. For the clinical diagnosis and therapy of malignancies, additional research into the involvement of COMMD proteins in cancer is beneficial.

Adverse Drug Reactions during COVID-19 Treatment A Comprehensive Analysis Focused on Hospitalized Patients, with the Use of a Survey in Cuba in 2020.

To evaluate the prevalence and type of adverse drug reactions (ADRs), together with associated risk factors, among Cuban COVID-19 patients treated with chloroquine (CQ), lopinavirritonavir (LPVr), or interferon A prospective descriptive analysis of ADRs was performed on 200 COVID-19 patients who were admitted consecutively to three hospitals in Havana and Pinar del Río from April to July 2020. Information on demographics, ADRs, outcomes, behavioral, and health-related factors was collected using a validated questionnaire and clinical records. Each potential ADR case was assessed for causality based on the WHO-UMC algorithm, concomitant drug influences, and the presence of any drug-drug interactions (DDI). The total frequency of ADRs was 55%, with predominantly gastrointestinal disorders and general symptoms (23% vs 20%). 95.1% of ADRs occurred within 10 days after treatment and 42 potential DDI in 55.5% of patients (61110) were observed. The prevalence of ADRs was 44%, 30.4%, and 26.4% for IFN The frequency of ADRs and potential DDI was high compared to their use during nonpandemic times (e.g., for malaria, HIV, or inflammatory diseases). The safety profile of these drugs when used for COVID-19 treatment showed similar characteristics. Comorbidities, age >37 years old, and female sex were associated with ADRs.

The Role of Interferon-α in Neurodegenerative Diseases A Systematic Review.

Neurodegenerative diseases (NDs) impose significant financial and healthcare burden on populations all over the world. The prevalence and incidence of NDs have been observed to increase dramatically with age. Hence, the number of reported cases is projected to increase in the future, as life spans continues to rise. Despite this, there is limited effective treatment against most NDs. Interferons (IFNs), a family of cytokines, have been suggested as a promising therapeutic target for NDs, particularly IFN-α, which governs various pathological pathways in different NDs. This systematic review aimed to critically appraise the currently available literature on the pathological role of IFN-α in neurodegenerationNDs. Three databases, Scopus, PubMed, and Ovid Medline, were utilized for the literature search. A total of 77 journal articles were selected for critical evaluation, based on the inclusion and exclusion criteria. The studies selected and elucidated in this current systematic review have showed that IFN-α may play a deleterious role in neurodegenerative diseases through its strong association with the inflammatory processes resulting in mainly neurocognitive impairments. IFN-α may be displaying its neurotoxic function via various mechanisms such as abnormal calcium mineralization, activation of STAT1-dependent mechanisms, and increased quinolinic acid production. The exact role IFN-α in these neurodegenerative diseases have yet to be determine due to a lack in more recent evidence, thereby creating a variability in the role of IFN-α. Future investigations should thus be conducted, so that the role played by IFN-α in neurodegenerative diseases could be delineated.

Long-term outcome of dolutegravir-containing regimens according to sex data from the ICONA study.

To compare the long-term risk of treatment failure of dolutegravir-based ART in men and women in a real-life setting. Persons living with HIV (PLWH) from the ICONA cohort were included if they had started dolutegravir in a two- or three-drug regimen as ART-naive or as virologically controlled ART-experienced. The primary endpoint was time to treatment failure (virologicalclinical failure or dolutegravir discontinuation). Secondary endpoints were time to dolutegravir discontinuation due to toxicity and to neuropsychiatric adverse events and time to virological failure. Cox regression analyses focused on differences in outcomes by sex. A total of 2304 PLWH (15% women) initiated dolutegravir-based therapy from ART-naive, and 1916 (19.8% women) while experienced. After a median follow-up of 2.2 (IQR 0.9-3.9) years in ART-naive and 2.4 (IQR 1.1-4.3) years in experienced, the 4-year cumulative probability of treatment failure was 33% (95% CI 30.5-35.1) and 20% (95% CI 17.8-22.3), respectively. In the multivariable analyses, in ART-naive the risk of treatment failure was higher for women, but not different after excluding women discontinuing dolutegravir for pregnancy concerns. We also observed a higher risk of discontinuation for toxicity in women (ART-naives Adjusted Hazard Ratio (AHR) 1.56% 95% CI 1.03-2.37 ART-experienced AHR 1.53% 95% CI 1.01-2.32), although the absolute 4-year probability was low 7.7% (95% CI 6.5-9.2) in ART-naive and 8.3% (95% CI 6.9-9.9) in experienced. In our cohort of PLWH treated with dolutegravir-based regimens and followed up for up to 4 years, we observed a low risk of treatment failure and no evidence for a difference by sex, after excluding discontinuation due to pregnancy concerns. However, we observed a higher risk of dolutegravir discontinuation for toxicity in women.

Pre-exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure an

Long-term evolution of comorbidities and their disease burden in individuals with and without HIV as they age analysis of the prospective AGE

People with HIV generally have more ageing-associated comorbidities than those without HIV. We aimed to establish whether the difference in comorbidities and their disease burden changes with ageing. In this prospective, longitudinal cohort study, we assessed comorbidities commonly associated with ageing every 2 years in 596 HIV-positive and 550 HIV-negative participants. HIV-positive participants were recruited from the HIV outpatient clinic of the Amsterdam University Medical Centres (Amsterdam, Netherlands). HIV-negative participants were recruited from the sexual health clinic and the Amsterdam Cohort Studies at the Public Health Service of Amsterdam (Amsterdam, Netherlands). Inclusion criteria were participants aged 45 years or older and, for HIV-negative participants, a documented HIV-negative antibody test. The mean number of comorbidities present over time was compared between groups by use of Poisson regression, accounting for dropout and death through joint survival models. Mean disability-adjusted life-years (DALYs) accrued during 2-year intervals were compared between groups by use of an exponential hurdle model. Between Oct 29, 2010, and Oct 9, 2012, participants were enrolled and then prospectively followed up until their last visit before Oct 1, 2018. 1146 participants were followed up for a median 5·9 years (IQR 5·7-6·0), during which 231 participants (20·2%) dropped out 145 (24·3%) of 596 HIV-positive and 86 (15·6%) of 550 HIV-negative. 38 (3·3%) of 1146 participants died 31 (5·2%) of 596 HIV-positive and seven (1·3%) of 550 HIV-negative. 24 HIV-positive and two HIV-negative participants died from ageing-associated comorbidities. 15 HIV-positive participants versus one HIV-negative participant died from non-AIDS malignancies. At inclusion, mean number of comorbidities was higher in HIV-positive participants (0·65) than in HIV-negative participants (0·32 p<0·0001). Mean number of comorbidities increased at similar rates over time rate ratio (RR) per year for HIV-positive participants 1·04 (95% CI 1·00-1·08), RR per year for HIV-negative participants 1·05 (1·01-1·08 p The larger comorbidity prevalence in HIV-positive participants aged 50-55 years on effective antiretroviral treatment than in HIV-negative participants increased similarly as participants aged and was associated with an increased risk of death, particularly of non-AIDS malignancies. Our findings reinforce the need for strategies to optimise prevention, screening, and early intervention. Netherlands Organization for Health Research and Development, Aidsfonds, Gilead Sciences, ViiV Healthcare, Janssen Pharmaceuticals, and Merck Co. For the Dutch translation of the abstract see Supplementary Materials section.

Acceptability and applicability of biometric iris scanning for the identification and follow up of highly mobile research participants living in fishing communities along the shores of Lake Victoria in Kenya, Tanzania, and Uganda.

Recruitment and retention of participants in research studies conducted in fishing communities remain a challenge because of population mobility. Reliable and acceptable methods for identifying and tracking participants taking part in HIV prevention and treatment research are needed. The study aims to assess the acceptability, and technical feasibility of iris scans as a biometric identification method for research participants in fishing communities. This was a cross-sectional study conducted in eight fishing communities in Kenya, Tanzania, and Uganda, with follow-up after one month in a randomly selected subset of participants. All consenting participants had their iris scanned and then responded to the survey. 1,199 participants were recruited. The median age was 33 Interquartile range (IQR) 24-42 years 56% were women. The overall acceptability of iris scanning was 99%, and the success rate was 98%. Eighty one percent (n 949) had a successful scan on first attempt, 116 (10%) on second and 113 (9%) after more than two attempts. A month later, 30% (n 341) of participants were followed up. The acceptability of repeat iris scanning was 99% (n 340). All participants who accepted repeat iris scanning had successful scans, with 307 (90%) scans succeeding on first attempt 25 (7%) on second attempt, and 8 (2%) after several attempts. The main reason for refusing iris scanning was fear of possible side effects of the scan on the eyes or body. The acceptability and applicability of biometric iris scan as a technique for unique identification of research participants is high in fishing communities. However, successful use of the iris scanning technology in research will require education regarding the safety of the procedure.

Temporal association of pre-pandemic perceived social support with psychological resilience and mental well-being during the COVID-19 pandemic among people with a history of injection drug use.

There are limited data on whether modifiable social factors foster psychological resilience and mental well-being among people who use drugs following Big Events. We examined the temporal association of pre-pandemic perceived social support with psychological resilience and negative mental health symptoms during the COVID-19 pandemic among people with a history of injection drug use. Between June and September 2020, we conducted a telephone survey among 545 participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study a community-based cohort of adults with a history of injection drug use. Leveraging data from study visits in 2018-early 2020, associations of pre-pandemic perceived social support with psychological resilience scores (range1-5) and the probability of negative mental health symptoms during the pandemic were assessed using multivariable linear and modified Poisson regression models, respectively. Participants median age was 58 years, 38.2% were female, 83.3% identified as Black, and 30.3% were living with HIV. During the pandemic, 14.5% had low (<3) resilience scores, 36.1% experienced anxiety, and 35.8% reported increased loneliness. Compared to participants in the lowest tertile of pre-pandemic social support, participants in the highest tertile had higher mean resilience scores (β 0.27 95% CI 0.12, 0.43), a lower probability of anxiety (prevalence ratio PR 0.71 95% CI 0.52, 0.96), and a lower probability of increased loneliness (PR 0.62 95% CI 0.45, 0.84). Pre-pandemic perceived social support was associated with greater psychological resilience and generally better mental well-being during the pandemic. Interventions that improve social support may foster psychological resilience and protect the mental well-being of people who use drugs, especially during periods of social disruption.

Utilizing first void urine for high-risk HPV testing for cervical cancer screening in HIV-positive women in Katete, Zambia.

The World Health Organization targets to screen 70% of women worldwide twice for cervical cancer by the year 2030, first by age of 35, and again by the age of 45. However, with the current low screening coverage in many developing countries, this may not be achieved because the invasive sampling method is unacceptable to some. In Zambia, for instance, despite the availability of free cervical cancer screening through the establishment of the Cervical Cancer Prevention Programme, some women are still reluctant to go for screening. First void urine sampling is non-invasive and thus has the potential to increase screening coverage. We aimed to determine the performance of first void urine for high-risk human papillomavirus DNA detection, the prevalence of high-risk HPV, and the acceptability of first void urine sampling. A comparative cross-sectional study was conducted among 100 HIV- infected women at St Francis Hospital in Zambia, attending the routine HIVAIDS services and cervical cancer screening. 17 mL of first void urine sample collected by each participant was immediately mixed with 3 mL of 0.5 M EDTA preservative solution before cervical sample collection by the clinician. For testing, 2 mL of first void urine and 1 mL of the cervical sample were tested using the GeneXpert platform. An interview-based questionnaire was used to gather data on the acceptability of first void urine sampling. Data was analyzed using Stata version 17. The mean age of the participants was 42.58 years (95% CI 40.98-44.19 SD 8.01). High-risk HPV prevalence was 34% (95% CI 24%-43.9%) in both cervical and first void urine samples. Sensitivity and specificity were 84.8% (95% CI 68.1%-94.9%) and 92.3% (83%-97.5%), respectively. There was 89.80% agreement between the samples (κ 0.77 95% CI 0.64-0.91). First void urine sampling was highly accepted. High-risk HPV DNA can be detected in first void urine samples using the GeneXpert, with a substantial agreement with cervical samples. An affordable preservative such as Ethylenediamine tetraacetic acid can prevent DNA degradation. With optimization, first void urine sampling has the potential to increase screening coverage.

HIV co-opts a cellular antiviral mechanism, activation of stress kinase PKR by its RNA, to enable splicing of revtat mRNA.

Activation of RNA-dependent stress kinase PKR, especially by viral double-stranded RNA, induces eukaryotic initiation factor 2 α-chain (eIF2α) phosphorylation, attenuating thereby translation. We report that this RNA-mediated negative control mechanism, considered a cornerstone of the cells antiviral response, positively regulates splicing of a viral mRNA. Excision of the large human immunodeficiency virus (HIV) revtat intron depends strictly on activation of PKR by the viral RNA and on eIF2α phosphorylation. Revtat mRNA splicing was blocked by viral PKR antagonists Vaccinia E3L and Ebola VP35, as well as by a trans-dominant negative mutant of PKR, yet enhanced by overexpressing PKR. Expression of non-phosphorylatable mutant eIF2αS51A, but not of wild type eIF2α, abrogated efficient splicing of revtat mRNA. By contrast, expression of eIF2αS51D, a phosphomimetic mutant of eIF2α, left revtat mRNA splicing intact. Unlike eIF2αS51A, eIF2αS51D does not inhibit eIF2α phosphorylation by activated PKR. All HIV mRNA species contain terminal trans-activation response (TAR) stem-loop sequences that potentially could activate PKR, yet even upon TAR deletion, HIV mRNA production remained sensitive to inhibitors of PKR activation. Bioinformatic and mutational analyses revealed a compact RNA pseudoknot upstream of 3-terminal TAR that promotes splicing by activating PKR. Supporting its essential role in control of splicing, this pseudoknot is conserved among diverse HIV and nonhuman primate SIVcpz isolates. The pseudoknot and 3-terminal TAR collaborate in mediating PKR-regulated splicing of revtat intron, the pseudoknot being dominant. Our results on HIV provide the first example of a virus co-opting activation of PKR by its RNA, a cellular antiviral mechanism, to promote splicing. They raise the question whether other viruses may use local activation of host kinase PKR through RNA elements within their genome to achieve efficient splicing of their mRNA. Our experiments reveal an indispensable role for eIF2α phosphorylation in HIV revtat mRNA splicing that accounts for the need for PKR activation.

Rapid-progressing progressive multifocal leukoencephalopathy in two patients newly diagnosed with HIV case series and review of literature.

The JC Polyomavirus (JCPyV) is a virus of global distribution and is usually kept under control by the immune system. In patients with AIDS, a latent JCPyV infection can reactivate and develop into progressive multifocal leukoencephalopathy (PML). Around half of the patients with PML die within 2 years since the diagnosis, yet in rare cases, the disease advances significantly quicker and seems to be insusceptible to any medical actions. In our clinic, we observed two cases of such course in HIV-positive patients in the AIDS stage. On admission, both patients had mild neurological symptoms such as dizziness, vision disturbances, and muscle weakness. Both had extremely low CD4 lymphocyte count (7 cellsμL, 40 cellsμL) and high HIV-1 viral load (VL) (50,324 copiesml, 78,334 copiesml). PML was confirmed by PCR for JCPyV DNA in cerebrospinal fluid (CSF) coupled with clinical and radiological features. Despite receiving though antiretroviral (ARV) treatment paired with intra-venous (IV) steroids, the disease progressed rapidly with neurological manifestations exacerbating throughout the few weeks following the admission. Eventually, both patients developed respiratory failure and died within less than 3 months after the onset of the neurological symptoms. Even though such curse of the disease is not common, it should be a warning to all how deadly both PML and AIDS can be and remind doctors to offer testing even to asymptomatic patients.

Higher Dietary Intake of Animal Protein Foods in Pregnancy Is Associated with Lower Risk of Adverse Birth Outcomes.

The prevalence of adverse birth outcomes is highest in resource-limited settings such as sub-Saharan Africa. Maternal consumption of diets with adequate nutrients during pregnancy may protect against these adverse outcomes. The objective was to determine the association between maternal dietary consumption of animal source foods (ASFs) and the risk of adverse birth outcomes among HIV-negative pregnant women in Tanzania. Using dietary intake data from 7564 HIV-negative pregnant women, we used Poisson regression with the empirical variance (generalized estimating equation) to estimate the RR of adverse birth outcomes-preterm birth, very preterm birth, small for gestational age (SGA), low birth weight (LBW), stillbirth, and neonatal death-for higher and lower frequency of ASF intake. Median daily dietary intake of animal protein was 17 g (IQR 1-48 g). Higher frequency of ASF protein intake was associated with lower risk of neonatal death (quartile 4 compared with quartile 1 RR 0.59 95% CI 0.38, 0.90 P-trend 0.01). Higher fish intake was associated with lower risk of very preterm birth (high tertile compared with low RR 0.76 95% CI 0.58, 0.99 P-trend 0.02). Any meat intake was protective of preterm birth (RR 0.73 95% CI 0.65, 0.82 P < 0.001), very preterm birth (P < 0.001), LBW (P < 0.001), and neonatal death (P 0.01) but was associated with increased risk of SGA (RR1.19 95% CI 1.01, 1.36 P 0.04). Any egg intake was protective of very preterm birth (RR 0.50 95% CI 0.31, 0.83 P 0.01) as compared with no egg intake. Finally, any dairy intake was associated with lower risk of preterm birth (RR 0.82 95% CI 0.68, 0.98 P 0.03) and very preterm birth (RR 0.53 95% CI 0.34, 0.84 P 0.01). Higher frequency of dietary intake of ASF is associated with lower risk of adverse birth outcomes in urban Tanzania. Promoting prenatal dietary intake of ASF may improve birth outcomes in this region and similar resource-limited settings.

HTLV seroprevalence in people using HIV pre-exposure prophylaxis in England.

HTLV-1 is predominantly a sexually-transmitted infection but testing is not mentioned in HIV-PrEP guidelines. We ascertained HTLV-1HTLV-2 seroprevalence amongst HIV-PrEP users in England. An unlinked anonymous seroprevalence study. Amongst 2015 HIV-PrEP users, 95% were men, 76% of white ethnicity and 83% had been born in Europe. There were no HTLV-1HTLV-2 seropositive cases (95% confidence interval 0% - 0.18%). There were no HTLV positive cases, likely reflecting the demographic of mostly white and European-born individuals. Similar studies are needed worldwide to inform public health recommendations for HIV-PrEP using populations, particularly in HTLV-endemic settings.

Prevention of recurrence of bacterial vaginosis using lactobacilli containing vaginal tablets among HIV infected women A randomized placebo controlled double-blinded phase IV trial.

The effectiveness of lactobacilli-containing vaginal tablets (VT) Bacterial Vaginosis (BV) recurrence prevention among HIV-infected women treated with standard oral Metronidazole in Pune, India was studied. HIV-infected women with confirmed BV diagnosis Nugent Score (NS)≥7 and Amsels criteria>3 were enrolled in a twelve-months, Double-Blind, Randomized, Placebo-controlled, phase IV study between 2018 and 2021. After a standard course of oral Metronidazole for seven days (400mg TID), women were randomized to either lactobacilli-containing or placebo VT arms to receive VTs for four months. BV recurrence was assessed after initial cure from BV. Of 464 HIV-infected women, 80 BV-confirmed women were enrolled. Retention was affected due to the COVID pandemic (six-month retention rates 78%). The cure was seen in 85% and 93.5% of participants from treatment and placebo arms respectively after 4 VT cycles. BV recurrence was seen in 41.4% and 44.8% in the treatment and placebo arm respectively with no significant difference in the two groups. The lactobacilli-containing VT was acceptable and safe however the addition of VT over standard oral Metronidazole did not show any additional benefit in the prevention of BV recurrence in HIV-infected women indicating the need for long-term randomized trials among them.

Neutron Reflectometry and Molecular Simulations Demonstrate HIV-1 Nef Homodimer Formation on Model Lipid Bilayers.

The HIV-1 Nef protein plays a critical role in viral infectivity, high-titer replication in vivo, and immune escape of HIV-infected cells. Nef lacks intrinsic biochemical activity, functioning instead through interactions with diverse host cell signaling proteins and intracellular trafficking pathways. Previous studies have established an essential role for Nef homodimer formation at the plasma membrane for most if not all its functions. Here we combined neutron reflectometry of full-length myristoylated Nef bound to model lipid bilayers with molecular simulations based on previous X-ray crystal structures of Nef homodimers. This integrated approach provides direct evidence that Nef associates with the membrane as a homodimer with its structured core region displaced from the membrane for partner protein engagement. Parallel studies of a dimerization-defective mutant, Nef-L112D, demonstrate that the helical dimerization interface present in previous crystal structures stabilizes the membrane-bound dimer. X-ray crystallography of the Nef-L112D mutant in complex with the SH3 domain of the Nef-associated host cell kinase Hck revealed a monomeric 11 complex instead of the 22 dimer complex formed with wild-type Nef. Importantly, the crystal structure of the Nef-L112D core and SH3 interface are virtually identical to the wild-type complex, indicating that this mutation does not affect the overall Nef fold. These findings support the intrinsic capacity of Nef to homodimerize at lipid bilayers using structural features present in X-ray crystal structures of dimeric complexes.

Use of cidofovir in a patient with severe mpox and uncontrolled HIV infection.

A 48-year-old man with poorly controlled HIV presented with severe human monkeypox virus (hMPXV) infection, having completed 2 weeks of tecovirimat at another hospital. He had painful, ulcerating skin lesions on most of his body and oropharyngeal cavity, with subsequent Ludwigs angina requiring repeated surgical interventions. Despite commencing a second, prolonged course of tecovirimat, he did not objectively improve, and new lesions were still noted at day 24. Discussion at the UK National Health Service England High Consequence Infectious Diseases Network recommended the use of 3% topical and then intravenous cidofovir, which was given at 5 mgkg the patient made a noticeable improvement after the first intravenous dose. He received further intravenous doses at 7 days and 21 days after the dose and was discharged at day 52. Cidofovir is not licensed for use in treatment of hMPXV infection. Data for cidofovir use in hMPXV are restricted to studies in animals. Four other documented cases of cidofovir use against hMPXV have been reported in the USA in 2022, but we present its first use in the UK. The scarcity of studies into the use of cidofovir in this condition clearly shows the need for robust studies to assess efficacy, optimum dosage, timing, and route of administration.

Drugs and Lactation Database (LactMed®)

Tenofovir is available in the U.S. in two forms, tenofovir disoproxil fumarate and tenofovir alafenamide. Both release tenofovir, but tenofovir disoproxil fumarate releases tenofovir in the bloodstream whereas tenofovir alafenamide enters cells before releasing tenofovir. Most published experience is with tenofovir disoproxil fumarate in HIV therapy and prophylaxis. Exposure of the breastfed infant to tenofovir is trivial in HIV-positive mothers and HIV-negative mothers treated for HIV prophylaxis or hepatitis B infection.1,2 Some data indicate that tenofovir milk levels decrease with time after delivery. Among HIV-positive mothers who have breastfed during tenofovir disoproxil fumarate therapy no infant adverse effects have occurred up to 2 years of age. Tenofovir alfenamide use results in even lower milk levels and infant dosages than tenofovir disoproxil fumarate. In the US and other countries where access to clean water and affordable replacement feeding are available, it is recommended that mothers living with HIV not breastfeed their infants to avoid postnatal transmission of HIV-1 infection. Pre-exposure prophylaxis (PrEP) regimens containing tenofovir are acceptable for use in HIV-negative nursing mothers.3 Maternal use of prophylactic vaginal tenofovir (investigational in the U.S.) also does not appear to present a risk to the breastfed infant.4 In hepatitis B, expert reviews of available data and most professional guidelines state that there is no justification for contraindicating the use of tenofovir during breastfeeding.5-9 One guideline suggests discussing the lack of long-term safety data with the mother.8 No differences exist in infection rates between breastfed and formula-fed infants born to hepatitis B-infected women, as long as the infant receives hepatitis B immune globulin and hepatitis B vaccine at birth.

Drugs and Lactation Database (LactMed®)

Etravirine is excreted in breastmilk in concentrations exceeding the maternal plasma and appears to increase in concentration over time. Until more information becomes available, an alternate agent may be preferred. In the US and other countries where access to clean water and affordable replacement feeding are available, it is recommended that mothers living with HIV not breastfeed their infants to avoid postnatal transmission of HIV-1 infection.

Drugs and Lactation Database (LactMed®)

Efavirenz is excreted into breastmilk and small amounts are found in the serum of some infants. Treatment of mothers of HIV-positive mothers with efavirenz does not appear to affect growth and development of their HIV-negative breastfed infants.

Various strategies for developing APOBEC3G protectors to circumvent human immunodeficiency virus type 1.

Host restriction factor APOBEC3G (A3G) efficiently restricts Vif-deficient HIV-1 by being packaged with progeny virions and causing the G to A mutation during HIV-1 viral DNA synthesis as the progeny virus infects new cells. HIV-1 expresses Vif protein to resist the activity of A3G by mediating A3G degradation. This process requires the self-association of Vif in concert with A3G proteins, protein chaperones, and factors of the ubiquitination machinery, which are potential targets to discover novel anti-HIV drugs. This review will describe compounds that have been reported so far to inhibit viral replication of HIV-1 by protecting A3G from Vif-mediated degradation.

Impact of treatment with direct-acting antivirals on inflammatory markers and autoantibodies in HIVHCV co-infected individuals.

HCV infection could have extrahepatic manifestations due to an aberrant immune response. HCVHIV co-infection increases such persistent immune activation. Aim of the present study is to describe the evolution of inflammatory markers used in clinical practice, mixed cryoglobulinemia (MC) and autoantibody reactivity in co-infected individuals who achieved sustained virological response (SVR) after DAA treatment. This prospective, observational study included all HIVHCV co-infected subjects who started any DAA regimen from 2015 to 2020. Samples for laboratory measurements (ferritin, C reactive protein, C3 and C4 fractions, rheumatoid factor, MC, anti-thyroglobulin Ab, anti-thyroid peroxidase Ab, ANCA, ASMA, anti-LKM, anti-DNA, AMA, ANA, T CD4 and CD8 cell count, and CD4CD8 ratio) were collected at baseline, after 4 weeks, at end of treatment, and at SVR12. The analysis included 129 individuals 51.9% with a F0-F3 fibrosis and 48.1% with liver cirrhosis. Cryocrit, C3 fraction, and rheumatoid factor significantly improved at week 4 ferritin, anti-thyroglobulin Ab, and C4 fraction at EOT total leukocytes count at SVR12. MC positivity decreased from 72.8% to 35.8% (p < .001). T CD4 cell slightly increased at SVR12, but with an increase also in CD8 resulting in stable CD4CD8 ratio. Autoantibody reactivity did not change significantly. ANA rods and rings positivity increased from 14.8% to 28.6% (p .099) they were observed in three subjects without exposure to RBV. DAA therapy may lead to improvement in inflammatory markers and MC clearance but without significant changes in autoantibodies reactivity and CD4CD8 ratio over a follow up of 12 weeks.

A Practical Approach to Bicyclic Carbamoyl Pyridones with Application to the Synthesis of HIV-1 Integrase Strand Transfer Inhibitors.

An efficient one-pot synthetic method has been developed for the preparation of bicyclic carbamoyl pyridones from the known common intermediate methyl 5-((2,4-difluorobenzyl)carbamoyl)-1-(2,2-dimethoxyethyl)-3-methoxy-4-oxo-1,4-dihydropyridine-2-carboxylate (

Discovery of Bis-Imidazoline Derivatives as New CXCR4 Ligands.

The chemokine receptor CXCR4 and its ligand CXCL12 regulate leukocyte trafficking, homeostasis and functions and are potential therapeutic targets in many diseases such as HIV-1 infection and cancers. Here, we identified new CXCR4 ligands in the CERMN chemical library using a FRET-based high-throughput screening assay. These are bis-imidazoline compounds comprising two imidazole rings linked by an alkyl chain. The molecules displace CXCL12 binding with submicromolar potencies, similarly to AMD3100, the only marketed CXCR4 ligand. They also inhibit anti-CXCR4 mAb 12G5 binding, CXCL12-mediated chemotaxis and HIV-1 infection. Further studies with newly synthesized derivatives pointed out to a role of alkyl chain length on the bis-imidazoline properties, with molecules with an even number of carbons equal to 8, 10 or 12 being the most potent. Interestingly, these differ in the functions of CXCR4 that they influence. Site-directed mutagenesis and molecular docking predict that the alkyl chain folds in such a way that the two imidazole groups become lodged in the transmembrane binding cavity of CXCR4. Results also suggest that the alkyl chain length influences how the imidazole rings positions in the cavity. These results may provide a basis for the design of new CXCR4 antagonists targeting specific functions of the receptor.

Predict the Effects of Dolutegravir (DTG) Plus Lamivudine (3TC) on Immunological Responses in People Living with HIV (PLWHIV).

Immune recovery in people living with HIV (PLWHIV) is a residual aspect of antiretroviral treatment (ART) in most patients, but in a non-negligible proportion of them, the CD4 lymphocytes count, or CD4CD8 ratio remains suboptimal. We performed a model of the immune response after 24 weeks of switching to a 2DR with DTG plus 3TC in a retrospective multicenter cohort of undetectable and experienced patients using significant predictor variables associated with the parameters or situations defined as success and failure. Clinical variables studied were CD4 and CD8 lymphocyte count, percentage of CD4, and CD4CD8 ratio. These parameters were assessed at baseline and 24 weeks after the switch. Based on the evolution of each variable, four categories of immune response and four categories of non-immune response were defined. Immune response was defined as CD4 count > 500 cellsmm In our different models of immunological response, the presence of stage of AIDS ( These models represent a proof of concept that could become a valuable tool for clinicians to predict the effects of DTG plus 3TC on immunological responses prior to the switch in undetectable pre-treated PLWHIV with immune dysfunction. The main predictors for immunological failure were late HIV diagnosis, stage of AIDS, and current age over 50 years. In contrast, starting with a normalized immune status was detected as stimulating or conducive to DTG plus 3TC treatment success.

Skin Manifestation of Human Monkeypox.

Monkeypox is a zoonotic infectious disease caused by the monkeypox virus (MPXV) infection, which is mainly manifested as characteristic rashes. It spreads mainly through direct skin-to-skin contact. In some cases, respiratory transmission occurs through contact with respiratory droplets when in close contact with an infected person for a long time. The monkeypox outbreak in 2022 frequently occurred in the MSM (men who have sex with men) population, raising concerns about whether monkeypox could be transmitted through sexual behavior. This article mainly reviews the research progress of skin manifestations of monkeypox, including typical and atypical rashes of monkeypox, and different skin manifestations in some special groups, such as children, pregnant women and individuals co-infected with HIV (human immunodeficiency virus) and MPXV. At present, dermatologists are not very familiar with the diagnosis and treatment of monkeypox, it is therefore necessary to review the skin manifestations of monkeypox, which can help clinicians diagnose the sporadic cases and monitor the occurrence of monkeypox early, particularly in people at higher risk of infection. Early clinical diagnosis and treatment can largely avoid serious complications and death from monkeypox.

The Peculiarity of Infection and Immunity Correlated with Guillain-Barré Syndrome in the HIV-Infected Population.

Guillain-Barré syndrome (GBS) can occur at all stages of human immunodeficiency virus (HIV) infection. HIV, cytomegalovirus (CMV), and varicella zoster virus (VZV) are the main infectious agents in HIV-positive GBS cases. These cases include acute and chronic HIV infection, immune reconstitution inflammatory syndrome (IRIS) shortly after anti-retroviral therapy (ART), those with ART interruption, or those with cerebrospinal fluids (CSF) HIV escape. The mechanisms are involved in both humoral and cellular immunities. Demyelinating and axonal neuropathies are the main pathological mechanisms in GBS. Presentation and prognosis are identical to those in patients without HIV infection. Typical or atypical clinical manifestations, CSF analysis, electrophysiological and pathological examination, and antiganglioside antibody detection can help diagnose GBS and classify its various subtypes. Intravenous immunoglobulin and plasma exchange have been used to treat GBS in HIV-positive patients with a necessary ART, while ganciclovir or foscarnet sodium should be used to treat ongoing CMV- or VZV-associated GBS. Steroids may be beneficial for patients with IRIS-related GBS. We reviewed HIV-positive cases with GBS published since 2000 and summarized their features to highlight the necessity of HIV testing among patients with GBS. Moreover, the establishment of a multidisciplinary team will guarantee diagnostic and therapeutic advantages.

CD8 Encephalitis in HIV A Review of This Emerging Entity.

Encephalitis is a life-threatening neurological condition with multiple causes in the setting of Human Immunodeficiency Virus (HIV). CD8 Encephalitis (CD8E) is a newly recognised condition which can present in an acute manner, with pertinent features including classical radiological findings with an intense brain parenchymal infiltration of CD8 T cells. This review attempted to clarify the symptomatology, distribution and determinants of this condition, as well as to examine its vast unknowns. A literature review was undertaken in July 2022, utilising the PubMed and Google Scholar databases. Papers published between 2006-2022 were reviewed. Eighteen papers, totalling 57 patients, were found and analysed. Statistical analysis was undertaken using Chi-squared and Wilcoxon rank-sum tests as appropriate, with In this review, 57 patients were identified, with a female (61%, 3456) and Black African (70%, 4057) preponderance. Females were more likely to present with headache ( CD8E represents a new and complex condition with few risk factors identified for its occurrence. The presenting symptoms are broad, but headache appears to be more common in females and more significantly associated with death. Though rare, CD8E is likely under-diagnosed, possibly due to overlapping features with other illnesses and lack of physician experience in its recognition and management. Corticosteroids demonstrate a clear mortality benefit, but more studies are required to determine their optimal dosing and duration, as well as the use of steroid-sparing agents. Further reviews should help to better determine the risk factors for the condition, as well as non-invasive biomarkers, to aid in diagnosis and help to predict poor prognosis and disease recurrence.

Evolution of Antiretroviral Drug Rilpivirine and Approach to Oncology.

Rilpivirine is an antiretroviral drug used to treat AIDS worldwide. The drug is a non-nucleoside reverse transcriptase inhibitor that halts the cDNA elongation process and, thus, the capacity of the HIV-1 virus to replicate. With the new wave of drug repurposing in recent years, rilpivirine has been studied in this regard. This drug is useful in Zika virus treatment, with in vivo results indicating regression in neuronal effects often associated with this infection. Several cancer types have also been researched, from breast to leukemia and pancreatic cancer, and rilpivirine has proved to have inhibitory effects in various cell lines with low concentrations, causing cellular death, apoptosis, and cell cycle arrest. The pathways are not yet established, but some works have hypothesized and demonstrated that rilpivirine causes inhibition of Aurora A kinase and has effects on the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway and the vascular endothelial growth factors-receptors (VEGFs-VEGFRs) pathway, which are known to be altered in cancer and tumors and can be targeted for cancer treatment. Further testing and clinical trials are needed, but this review demonstrates the potential of rilpivirines repurposing for cancer treatment.

Plant Coumarins with Anti-HIV Activity Isolation and Mechanisms of Action.

This review summarizes and systematizes the literature on the anti-HIV activity of plant coumarins with emphasis on isolation and the mechanism of their antiviral action. This review summarizes the information on the anti-HIV properties of simple coumarins as well as annulated furano- and pyranocoumarins and shows that coumarins of plant origin can act by several mechanisms inhibition of HIV reverse transcriptase and integrase, inhibition of cellular factors that regulate HIV-1 replication, and transmission of viral particles from infected macrophages to healthy ones. It is important to note that some pyranocoumarins are able to act through several mechanisms or bind to several sites, which ensures the resistance of these compounds to HIV mutations. Here we review the last two decades of research on the anti-HIV activity of naturally occurring coumarins.

Time of Day Influences Concentrations of Total Protein and Albumin in Cerebrospinal Fluid in HIV.

The accumulation of soluble proteins and metabolites during wakefulness and their clearance during sleep via the glymphatic system occurs in healthy adults and is disturbed in some neurological conditions. Such diurnal variations in the cerebrospinal fluid (CSF) proteins produced outside the central nervous system and entering via the blood-brain barrier (BBB) have not been evaluated in people with HIV (PWH). CSF and blood were collected in 165 PWH at six US centers between 2003 and 2007. The time of collection was compared to CSF albumin, globulin, and total protein concentrations using bivariate and multivariate regression. Participants all took antiretroviral therapy (ART) and were mostly middle-aged (median age 44.0 years) men (78.8%), with AIDS (77.0%), plasma HIV RNA ≤ 200 copiesmL (75.8%), and immune recovery (median CD4 T-cell count 414µL). CSF was collected at median 110 p.m. (range 900 a.m. to 520 p.m.) and within a median of 15 min of blood collection. A later time of CSF collection was associated with higher total protein (

Both ATM and DNA-PK Are the Main Regulators of HIV-1 Post-Integrational DNA Repair.

The integration of a DNA copy of an HIV-1 RNA genome into the host genome, carried out by the viral enzyme integrase, results in the formation of single-stranded gaps in cellular DNA that must be repaired. Here, we have analyzed the involvement of the PI3K kinases, ATM, ATR, and DNA-PKcs, which are important players in the DNA damage response (DDR) in HIV-1 post-integrational DNA repair (PIR). The participation of the DNA-PK complex in HIV-1 PIR has been previously shown, and the formation of a complex between the viral integrase and the DNA-PK subunit, Ku70, has been found to be crucial for efficient PIR. Now, we have shown that the inhibition of both DNA-PKcs and ATM, but not ATR, significantly reduces PIR efficiency. The activation of both kinases is a sequential process, where one kinase, being activated, activates the other, and it occurs simultaneously with the integration of viral DNA. This fact suggests that the activation of both kinases triggers PIR. Most interestingly, the activation of not only DNA-PKcs, but also ATM depends on the complex formation between integrase and Ku70. The elucidation of the interactions between viruses and DDR is important both for understanding the modulation of host cell functions by these pathogens and for developing new approaches to combat viral infections.

The Effects of Viruses on Insulin Sensitivity and Blood-Brain Barrier Function.

In this review manuscript, we discuss the effects of select common viruses on insulin sensitivity and blood-brain barrier (BBB) function and the potential overlapping and distinct mechanisms involved in these effects. More specifically, we discuss the effects of human immunodeficiency virus (HIV), herpes, hepatitis, influenza, respiratory syncytial virus (RSV), and SARS-CoV-2 viruses on insulin sensitivity and BBB function and the proposed underlying mechanisms. These viruses differ in their ability to be transported across the BBB, disrupt the BBB, andor alter the function of the BBB. For RSV and SARS-CoV-2, diabetes increases the risk of infection with the virus, in addition to viral infection increasing the risk for development of diabetes. For HIV and hepatitis C and E, enhanced TNF-a levels play a role in the detrimental effects. The winter of 2022-2023 has been labeled as a tridemic as influenza, RSV, and COVID-19 are all of concern during this flu season. There is an ongoing discussion about whether combined viral exposures of influenza, RSV, and COVID-19 have additive, synergistic, or interference effects. Therefore, increased efforts are warranted to determine how combined viral exposures affect insulin sensitivity and BBB function.

Cabotegravir Exposure of Zebrafish (

As most new medications, Cabotegravir (CAB) was recently approved as an antiretroviral treatment of HIV infection without in-depth safety information on in utero exposure. Although no developmental toxicity in rats and rabbits was reported, recent studies demonstrated that CAB decreases pluripotency of human embryonic stem cells. CAB exposure effects during development were assessed in zebrafish embryos by the Fish Embryo Toxicity test after exposure at subtherapeutic concentrations up to 25× the human C

HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular Vesicles.

Extracellular vesicles (EVs) and their cargo have been studied intensively as potential sources of biomarkers in HIV infection however, their DNA content, particularly the mitochondrial portion (mtDNA), remains largely unexplored. It is well known that human immunodeficiency virus (HIV) infection and prolonged antiretroviral therapy (ART) lead to mitochondrial dysfunction and reduced mtDNA copy in cells and tissues. Moreover, mtDNA is a well-known damage-associated molecular pattern molecule that could potentially contribute to increased immune activation, oxidative stress, and inflammatory response. We investigated the mtDNA content of large and small plasma EVs in persons living with HIV (PLWH) and its implications for viral replication, ART use, and immune status. Venous blood was collected from 196 PLWH, ART-treated or ART-naïve (66 with ongoing viral replication, ≥20 copiesmL), and from 53 HIV-negative persons, all recruited at five HIV testing or treatment centers in Burkina Faso. Large and small plasma EVs were purified and counted, and mtDNA level was measured by RT-qPCR. Regardless of HIV status, mtDNA was more abundant in large than small EVs. It was more abundant in EVs of viremic than aviremic and control participants and tended to be more abundant in participants treated with Tenofovir compared with Zidovudine. When ART treatment was longer than six months and viremia was undetectable, no variation in EV mtDNA content versus CD4 and CD8 count or CD4CD8 ratio was observed. However, mtDNA in large and small EVs decreased with years of HIV infection and ART. Our results highlight the impact of viral replication and ART on large and small EVs mtDNA content. The mechanisms underlying the differential incorporation of mtDNA into EVs and their effects on the surrounding cells warrant further investigation.

Convergent Evolution Dynamics of SARS-CoV-2 and HIV Surface Envelope Glycoproteins Driven by Host Cell Surface Receptors and Lipid Rafts Lessons for the Future.

Although very different, in terms of their genomic organization, their enzymatic proteins, and their structural proteins, HIV and SARS-CoV-2 have an extraordinary evolutionary potential in common. Faced with various selection pressures that may be generated by treatments or immune responses, these RNA viruses demonstrate very high adaptive capacities, which result in the continuous emergence of variants and quasi-species. In this retrospective analysis of viral proteins, ensuring the adhesion of these viruses to the plasma membrane of host cells, we highlight many common points that suggest the convergent mechanisms of evolution. HIV and SARS-CoV-2 first recognize a lipid raft microdomain that acts as a landing strip for viral particles on the host cell surface. In the case of mucosal cells, which are the primary targets of both viruses, these microdomains are enriched in anionic glycolipids (gangliosides) forming a global electronegative field. Both viruses use lipid rafts to surf on the cell surface in search of a protein receptor able to trigger the fusion process. This implies that viral envelope proteins are both geometrically and electrically compatible to the biomolecules they select to invade host cells. In the present study, we identify the surface electrostatic potential as a critical parameter controlling the convergent evolution dynamics of HIV-1 and SARS-CoV-2 surface envelope proteins, and we discuss the impact of this parameter on the phenotypic properties of both viruses. The virological data accumulated since the emergence of HIV in the early 1980s should help us to face present and future virus pandemics.

Involvement of TRPM7 in Alcohol-Induced Damage of the Blood-Brain Barrier in the Presence of HIV Viral Proteins.

Ethanol (EtOH) exerts its effects through various protein targets, including transient receptor potential melastatin 7 (TRPM7) channels, which play an essential role in cellular homeostasis. We demonstrated that TRPM7 is expressed in rat brain microvascular endothelial cells (rBMVECs), the major cellular component of the blood-brain barrier (BBB). Heavy alcohol drinking is often associated with HIV infection, however mechanisms underlying alcohol-induced BBB damage and HIV proteins, are not fully understood. We utilized the HIV-1 transgenic (HIV-1Tg) rat to mimic HIV-1 patients on combination anti-retroviral therapy (cART) and demonstrated TRPM7 expression in rBMVECs wass lower in adolescent HIV-1Tg rats compared to control animals, however control and HIV-1Tg rats expressed similar levels at 9 weeks, indicating persistent presence of HIV-1 proteins delayed TRPM7 expression. Binge exposure to EtOH (binge EtOH) decreased TRPM7 expression in control rBMVECs in a concentration-dependent manner, and abolished TRPM7 expression in HIV-1Tg rats. In human BMVECs (hBMVECs), TRPM7 expression was downregulated after treatment with EtOH, HIV-1 proteins, and in combination. Next, we constructed in vitro BBB models using BMVECs and found TRPM7 antagonists enhanced EtOH-mediated BBB integrity changes. Our study demonstrated alcohol decreased TRPM7 expression, whereby TRPM7 could be involved in the mechanisms underlying BBB alcohol-induced damage in HIV-1 patients on cART.

Understanding Sexualized Drug Use Substances, Reasons, Consequences, and Self-Perceptions among Men Who Have Sex with Other Men in Spain.

Sexualized drug use (SDU) has been identified as a health risk factor among gay, bisexual, and other men who have sex with men (GBMSM). This study aimed to analyze the associations between SDU frequency and a broad set of substances, motives, consequences, and self-perceptions. Sampling was conducted through an online survey. The final sample consisted of 185 GBMSM aged between 18 and 78 years old (mean age 38.38, SD 11.52) who engaged in SDU. We analyzed the frequency of SDU in terms of practicing it once, moderately (once a month or less or a few times a month), or frequently (from once a week to daily) during the previous 18 months. A questionnaire was administered through which sociodemographic variables, substances, reasons, consequences, and self-perceptions of SDU practice were analyzed. Participants who did so frequently were significantly more likely to use mephedrone, methamphetamine, and GHBGBL than those who performed SDU less often (large effect sizes). In addition, habitual SDU was associated with motivations to achieve pleasurable emotions and sensations and manage negative feelings. Health implications, such as blackout moments, were also significantly related to frequent SDUs. Finally, those who practiced frequent SDU perceived it as a severe problem and wanted to control it. These data indicate the importance of raising awareness of chemsex as a public health problem among GBMSM. Specific identification, education, and prevention programs need to be strengthened to reduce the incidence of the most undesirable implications of SDU among GBMSM.

Sexual Behavior and Perceived Loneliness in Elderly People Living with HIV in China during the COVID-19 Pandemic.

The proportion of elderly people living with HIV (PLHIV) is increasing in China. To advance targeted interventions and substantially improve their quality of life, we investigate indicators of loneliness and sexual behavior among elderly PLHIV in 10 districtscounties in China during the COVID-19 pandemic. The demographic information and laboratory test results of the potential respondents were initially collected from the China Information System for Disease Control and Prevention. A two-stage stratified cluster sampling was used. The questionnaire survey was individually provided to all PLHIV aged 60. We recruited 1017 valid respondents with a median age of 66 years (interquartile range of 63-71), of which 776 (76.3%) were male. Overall, 341 respondents (33.5%) lived alone, and 304 (29.9%) felt lonely. A total of 726 respondents (71.4%) informed others of their HIV diagnosis. Among the 726 respondents, children were the most common group with whom the older people shared their HIV infection status, accounting for 82.9%. Approximately 20% of the older PLHIV engaged in sexual behavior in the last year, and 70% reported not using condoms. A significantly greater risk of loneliness was found among the females (AOR 1.542, CI 1.084, 2.193), those who suffered discrimination from informed people (AOR 4.719, CI 2.986, 7.459), were diagnosed <1 year prior (AOR 2.061, CI 1.345, 3.156), those living alone (AOR 2.314, CI 1.632, 3.280), those having no friends (AOR 1.779, CI 1.327, 2.386), and those who had a divorced or widowed marital status (AOR 1.686, CI 1.174, 2.421). Compared with non-lonely participants, the lonely participants were more likely to have a rural registered residence, a lower education level, no friends, be divorced or widowed, live alone, and lack knowledge of smartphones and reproductive health. The influence of COVID-19 had caused social activities to be more confined to the community, which impacts elderly HIV patients suffering from severe discrimination within families and communities.

Very High Incidence of

The rise in sexually transmitted infections and chemsex has led to syndemy with HIV, partly due to common routes of transmission and clustered transmissions. Despite this, barriers to STI care and PrEP still remain. We sought to determine whether MSM at low risk for HIV infection were also at low risk for other STIs. The study group was tested for HIV, HCV, and Despite a lower risk for HIV acquisition, the study group was at a very high risk for other STIs, and this risk remained high throughout the study. Patients and medical professionals should be aware of syphilis, gonorrhea, and chlamydiosis transmission risks, and screening should be performed accordingly. Prophylactic programs need to be updated to specifically include lower-risk individuals.

Molecular Transmission Network of Newly Reported HIV Infections in Pengzhou, Sichuan Province A Study Based on Genomics and Spatial Epidemiology.

The objective of this study was to understand the molecular transmission characteristics of newly reported HIV infections in the city of Pengzhou, Sichuan Province, to analyze the risk factors of transmission network and spatial clustering and the transmission characteristics, and to provide a scientific basis for precision prevention and intervention. Anticoagulated whole blood was collected from newly reported HIV infections in Pengzhou from March 2019 to August 2021. After the plasma was isolated, the HIV-1 pol gene was amplified and sequenced by reverse transcriptase polymerase chain reaction (PCR). The obtained gene sequences were used to construct a maximum likelihood phylogenetic tree for the analysis of virus subtypes, and a molecular transmission network was constructed using the genetic distance method to evaluate the transmission pattern of people living with HIVAIDS in Pengzhou. A logistic regression model was used to find out the potential risk factors for entering the molecular transmission network with the number of nodes ≥ 2. Spatial analysis is used to show the geographical pattern of the proportion of newly reported HIV infections entering the molecular transmission network, and a flow map is used to show the intensity of transmission within and between townships. A total of 463 newly reported HIV-infection sequences were obtained in this study, including 237 cases (51.19%) of CRF01 AE, 159 cases (34.34%) of CRF07BC, 45 cases (9.72%) of B, 15 cases (3.24%) of CRF08BC and 7 cases (1.5%) of others. The number of clusters was the highest when the gene distance was 0.009, with a total of 246 sequences entering the network, forming 54 clusters, and the network entry rate was 55.36%. There were 170 sequences with more than two nodes in the network sequence. The logistic regression showed that compared with age < 50 years old, age ≥ 50 years old has a higher risk of transmission (OR 3.43, 95% CI 2.06-5.71) compared with farmers, the risk of transmission within industry is lower (OR 0.046, 95% CI 0.25-0.87) and compared with CRF07BC, CRF01AE (OR 6.09, 95% CI 3.60-10.30) and B (OR 20.31, 95% CI 8.94-46.13) had a higher risk of transmission. Men aged ≥ 50 years are mainly clustered with women between 50 and 70 years of age. In addition to being clustered with gay men, there are nine (50%) and three (16.7%) chains of transmission between gay men and heterosexual men and women, respectively. In the geographical space, there is no hot spot clustering of the molecular propagation network. The subtype B was mainly distributed in the town of Tianpeng and formed transmission networks in eastern Pengzhou0020CRF01AE is mainly distributed in the town of Lichun and formed transmission networks in the west and north of Pengzhou. This study reveals the characteristics and influencing factors of molecular network transmission in the region, as well as the spatial transmission characteristics of newly reported HIV infections in recent years, and reveals the geographical differences in HIV-1 transmission. The results provide a scientific basis for the development of local AIDS-specific intervention measures.

HIV-Exposed Uninfected Children A Systematic Review on Psychological Well-Being and Association with School Performances in Africa.

There is a growing number of children affected by HIV in Africa. Research on HIV-exposed uninfected children (HEU) is also growing. This systematic review focuses on the psychological well-being of HEU and its association with school intervention, outcomes, and enrollment in the African context, which is where the rate of HIV reaches its highest levels. Research on public databases was conducted according to PRISMA standards. Only studies on HEU primary school children in Africa, both quantitative and qualitative, were included. Out of 1510 papers retrieved, 50 met the inclusion criteria. These studies demonstrate that HEU children are more likely to perform worse in school compared to their counterparts who were not exposed to HIV and to show poorer concentration in the classroom. Children with parents suffering from AIDS are worried for them and have to take household responsibility, resulting in school dropouts, juvenile work, and risky behaviors. Few interventions have been conducted in the school environment with some of them being successful therefore, future research should involve schools to create an inclusive environment where HEU children could enhance their potential and improve their psychological health.

Effectiveness, Acceptability and Feasibility of Technology-Enabled Health Interventions for Adolescents Living with HIV in Low- and Middle-Income Countries A Systematic Review.

Adolescents living with HIV (ALHIV) are challenged to remain adherent and engaged in HIV care. Technology-enabled interventions can be used to optimize healthcare delivery to adolescents. The largest proportion of ALHIV resides in sub-Saharan Africa. This review synthesized the evidence for the effectiveness, acceptability, and feasibility of technology-enabled health interventions for ALHIV in low and middle-income countries (LMIC). Eight electronic databases (Ebscohost, CINAHL, ERIC, MEDLINE, PubMed, SCOPUS, Science Direct, and Sabinet) and Google Scholar were searched to identify studies in LMIC published from 2010 to 2022. Quantitative and qualitative studies reporting on technology-enabled health interventions for predominantly adolescents (10-19 years) were included. The review was performed, and findings were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols. The review was registered with PROSPERO CRD42022336330. There is weak evidence that technology-enabled health interventions for ALHIV in LMIC improve treatment outcomes. However, most interventions appear to be acceptable and feasible. There is a need to ensure that technology-enabled interventions have a strong theoretical base. Larger studies with rigorous evaluation designs are needed to determine the effects of these interventions on the health outcomes of ALHIV in LMIC.

A Qualitative Exploration of Factors Influencing Non-Use of Sexual Reproductive Health Services among University Students in South Africa.

(1) Background There is growing concern in South Africa about risky sexual behaviour, sexual transmitted infections (STIs), and unplanned pregnancy among young people. Many sexually active students engage in several risky behaviours, including sex with multiple sexual partners, low condom use, and low contraceptive use. This paper qualitatively explores factors influencing non-use of sexual reproductive health services by students at Mangosuthu University of Technology in South Africa (MUT). (2) Methods Data was collected through 20 in-depth interviews with MUT students and subjected to inductive thematic analysis. Informed consent was obtained before all data collection. (3) Results The main themes identified were risky sexual behaviours translating to multiple intimate partners, perceived quality of condom use, perceived benefits of contraceptives, negotiating safer sex with partners, developing a greater sense of autonomy, alcohol and drug abuse, perceived benefits of health education provided by the MUT, and lack of open communication. (4) Conclusions The findings suggest that university students need multi-faceted interventions designed to address challenges with risky sexual behaviours including knowledge and benefits of condom and contraceptive use to prevent STIs and unwanted pregnancies, as well as providing psychosocial interventions to support these students autonomy.

Multimodality Imaging in HIV-Associated Cardiovascular Complications A Comprehensive Review.

Human immunodeficiency virus (HIV) infection is a leading cause of mortality and morbidity worldwide. The introduction of antiretroviral therapy (ART) has significantly reduced the risk of developing acquired immune deficiency syndrome and increased life expectancy, approaching that of the general population. However, people living with HIV have a substantially increased risk of cardiovascular diseases despite long-term viral suppression using ART. HIV-associated cardiovascular complications encompass a broad spectrum of diseases that involve the myocardium, pericardium, coronary arteries, valves, and systemic and pulmonary vasculature. Traditional risk stratification tools do not accurately predict cardiovascular risk in this population. Multimodality imaging plays an essential role in the evaluation of various HIV-related cardiovascular complications. Here, we emphasize the role of multimodality imaging in establishing the diagnosis and aetiopathogenesis of various cardiovascular manifestations related to chronic HIV disease. This review also provides a critical appraisal of contemporary data and illustrative cases.

Examining the Correlates of HIV Testing for Venezuelan Migrants in Trinidad.

An important preventive measure in the fight against the HIV epidemic is the adoption of HIV testing. The government of the Republic of Trinidad and Tobago conducted a registration exercise in 2019 for undocumented migrants and refugees from Venezuela residing in the country. These migrants were allowed access to the public health system. In this study, we observed the correlates of HIV testing in Venezuelan migrants residing in Trinidad. A convenience sample of

An Engaged Community of Faith to Decrease HIV Stigma in the U.S. South.

Community members from a city in the U.S. Deep South identified root causes of HIV racial disparities, including stigma. This meeting report describes how we developed and implemented a conference series to address HIV stigma. We used community feedback and bidirectional learning to host two meetings in observance of National HIV Testing Day (June 2021) and National Southern HIVAIDS Awareness Day (August 2021). We established a 10-member organizing committee workgroup that met monthly to plan the Faith Summit in honor of National Black HIV Awareness Day (February 2022). Lessons learned include (a) the effectiveness of different community engagement strategies, including participatory evaluative approaches, and (b) strategies to maintain engagement and increase participation, such as reliance on personal and professional networks and prompting the community about forthcoming interventions. Sustaining a conference series to end HIV stigma requires commitment and inclusive participation. This collaborative project offers additional evidence that faith communities can be a part of the solution to ending the HIV epidemic and related health disparities.

Awareness, Utilization and Perception of Sexually Transmitted Infections Services Provided to Out-of-School-Youth in Primary Health Facilities in Tshwane, South Africa.

Despite the availability of different health care initiatives and interventions, young people are still faced with barriers in accessing reproductive health care services thus, they are exposed to health-related issues such as sexually transmitted infections. To determine the awareness, utilization and perceptions about sexually transmitted infections services provided to out-of-school-youth in primary health facilities in the Tshwane district, Gauteng Province, South Africa. The study employed a quantitative, cross-sectional descriptive survey with a sample size of 219 to determine the level of awareness, utilization and perceptions about sexually transmitted infections services provided to out-of-school-youth in Tshwane district. Out-of-school-youth between the ages of 18-24 years participated in the study. Most of the participants (90.8%, n 199) were female. Service utilization was high in females compared to their male counterparts. There is availability of youth-friendly services in primary health care facilities, however, the level of service utilization among young people is still a challenge evidenced by 12.1% (n 74) of participants who never sought treatment for STIs, although they had STI symptoms. Furthermore, 52.0% reported that they were not happy with the health services they received when they had STIs. These findings clearly indicate a gap in service delivery for young people regarding reproductive health issues thus, the low health care seeking behavior among the youth. Condom use was 69.1% andor inconsistently used among the youth about 80% of the participants had low perceptions of the risk of contracting STIs. The self-reported risks of HIV and AIDS was 46.8%. Approximately 20% reported that they would not refuse to have sex if their partner did not want to use condoms. These findings showed risky behavior among the participants, and shows that the level of awareness about the risk of contracting STIs is still poor. Irrespective of facilities with youth-friendly services, out-of-school-youth still display poor perceptions about sexually transmitted infections services due to health care providers attitudes, limited resources, and working hours. Furthermore, the level of awareness regarding sexually transmitted infections is poor, hence the display of risky sexual behaviors.

Encouraging and Reinforcing Safe Breastfeeding Practices during the COVID-19 Pandemic.

Promote safe breastfeeding during the pandemic. All participants were encouraged to request safe breastfeeding education from their prenatal provider. Pregnant mothers received appropriate breastfeeding and COVID-19 safe breastfeeding education in line with the CDCs COVID-19 breastfeeding guidelines. Data were obtained from 39 mothers attending Nashville General Hospital pediatric well-baby clinics (Group I from December 2019 to June 2020) and 97 pregnant women attending prenatal clinics (Group II from July 2020 to August 2021). The participants ages ranged from 15 to 45 years, with a mean of 27.5 ± 6.2. The women in both groups were similar in age, education, employment, and breastfeeding experience. They were equally unlikely to use face masks at home even while receiving guests or holding their babies. Although 121 (89.0%) women claimed face mask use while shopping, the rate for never doing so was 7 (18.0%) vs. 8 (8.3%) ( The mothers were not more knowledgeable regarding breastfeeding safely one year into the COVID-19 pandemic. Conflicting lay information can create healthy behavior ambivalence, which can be prevented by health professionals confidently advising mothers to wear face masks when breastfeeding, restricting visitors and outings, and accepting COVID-19 vaccination. This pandemic remains an open opportunity to promote and encourage breastfeeding to every mother as the default newborn feeding method.

Immune Cells Release MicroRNA-155 Enriched Extracellular Vesicles That Promote HIV-1 Infection.

The hallmark of HIV-1 infection is the rapid dysregulation of immune functions. Recent investigations for biomarkers of such dysregulation in people living with HIV (PLWH) reveal a strong correlation between viral rebound and immune activation with an increased abundance of extracellular vesicles (EVs) enriched with microRNA-155. We propose that the activation of peripheral blood mononuclear cells (PBMCs) leads to an increased miR-155 expression and production of miR-155-rich extracellular vesicles (miR-155-rich EVs), which can exacerbate HIV-1 infection by promoting viral replication. PBMCs were incubated with either HIV-1 (NL4.3Balenv), a TLR-78 agonist, or TNF. EVs were harvested from the cell culture supernatant by differential centrifugation, and RT-qPCR quantified miR-155 in cells and derived EVs. The effect of miR-155-rich EVs on replication of HIV-1 in incubated PBMCs was then measured by viral RNA and DNA quantification. HIV-1, TLR78 agonist, and TNF each induced the release of miR-155-rich EVs by PBMCs. These miR-155-rich EVs increased viral replication in PBMCs infected in vitro. Infection with HIV-1 and inflammation promote the production of miR-155-rich EVs, enhancing viral replication. Such autocrine loops, therefore, could influence the course of HIV-1 infection by promoting viral replication.

Prevalence of HIV and Viral Hepatitis Markers among Healthcare Workers in the Republic of Guinea.

Healthcare workers are much more likely to be infected with HIV and hepatitis viruses compared to the general population. Although healthcare workers are more aware of HIV and hepatitis viruses, several countries in Africa lack a comprehensive grasp of disease routes and transmission risks. The aim of this study was to assess the prevalence of the serological and molecular biological markers of HIV and viral hepatitis among healthcare workers in the Republic of Guinea. The study material was 74 blood serum samples collected from healthcare workers who received additional training at the Institute of Applied Biological Research of Guinea (IRBAG, Kindia, Republic of Guinea). The markers examined included HBsAg, HBeAg, anti-HBs IgG, anti-HBcore IgG, anti-HCV qualitative determination, anti-HEV IgM and IgG, anti-HAV IgM and IgG, and anti-HIV. For viral DNA and RNA detection, nucleic acids were extracted from blood serum, and viral presence was inferred using real-time PCR with hybridization fluorescence detection. A high prevalence of viral hepatitis B markers was shown, and significantly fewer cases of viral hepatitis C and HIV were detected. Almost all examined medical workers had anti-HAV IgG antibodies, but no antibodies to hepatitis E virus. Apparently, the identified markers depend on the general prevalence of certain pathogens in the region and are associated with the traditions and characteristics of the countrys residents.

Effect of the Hematocrit and Storage Temperature of Dried Blood Samples in the Serological Study of Mumps, Measles and Rubella.

Dried blood spots (DBSs) are an economical and convenient alternative to serumplasma, which allow for the serological and molecular study of different pathogens. Sixty-four blood samples were collected by venipuncture and spotted onto Whatman™ 903 cards to evaluate the utility of DBSs and the effect of the storage temperature for 120 days after sample collection to carry out serological diagnosis. Mumps, measles and rubella IgG were investigated from DBSs and plasma using an automated chemiluminescent immunoassay. Using a calculated optimal cut-off value, the serological evaluation of mumps, measles and rubella using DBSs achieved high sensitivity (100%, 100% and 82.5%, respectively) and specificity (100%, 87.5% and 100%, respectively). The correlation observed between the plasma and the DBSs processed after sample collection was high (0.914-0.953) for all antibodies studied, both considering hematocrit before sample elution or not. For the different storage conditions, the correlation with plasma was high at 4 °C (0.889-0.925) and at -20 °C (0.878-0.951) but lower at room temperature (0.762-0.872). Measles IgG results were more affected than other markers when DBSs were stored at any temperature for 120 days. To summarize, hematocrit does not affect the processing of DBSs in the study of serological markers of mumps, measles and rubella. DBS stability for serological diagnosis of mumps and rubella is adequate when samples are stored at -20 °C or 4 °C, but not at room temperature, for a period of 4 months.

Unraveling the Complex Interconnection between Specific Inflammatory Signaling Pathways and Mechanisms Involved in HIV-Associated Colorectal Oncogenesis.

The advancement of HIV treatment has led to increased life expectancy. However, people living with HIV (PLWH) are at a higher risk of developing colorectal cancers. Chronic inflammation has a key role in oncogenesis, affecting the initiation, promotion, transformation, and advancement of the disease. PLWH are prone to opportunistic infections that trigger inflammation. It has been documented that 15-20% of cancers are triggered by infections, and this percentage is expected to be increased in HIV co-infections. The incidence of parasitic infections such as helminths, with

HPV Type Distribution in Benign, High-Grade Squamous Intraepithelial Lesions and Squamous Cell Cancers of the Anus by HIV Status.

The incidence of anal cancer is increasing, especially in high-risk groups, such as PLWH. HPV 16, a high-risk (HR) HPV genotype, is the most common genotype in anal high-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) in the general population. However, few studies have described the distribution of HR HPV genotypes other than HPV 16 in the anus of PLWH. HPV genotyping was performed by DNA amplification followed by dot-blot hybridization to identify the HR and low-risk (LR) genotypes in benign anal lesions (n 34), HSIL (n 30), and SCC (n 51) of PLWH and HIV-negative individuals. HPV 16 was the most prominent HR HPV identified, but it was less common in HSIL and SCC from PLWH compared with HIV-negative individuals, and other non-HPV 16 HR HPV (non-16 HR HPV) types were more prevalent in samples from PLWH. A higher proportion of clinically normal tissues from PLWH were positive for one or more HPV genotypes. Multiple HPV infection was a hallmark feature for all tissues (benign, HSIL, SCC) of PLWH. These results indicate that the development of anal screening approaches based on HPV DNA testing need to include non-16 HR HPVs along with HPV 16, especially for PLWH. Along with anal cytology, these updated screening approaches may help to identify and prevent anal disease progression in PLWH.

Incorporating end-users voices into the development of an implant for HIV prevention a discrete choice experiment in South Africa and Zimbabwe.

Input from end-users during preclinical phases can support market fit for new HIV prevention technologies. With several long-acting pre-exposure prophylaxis (PrEP) implants in development, we aimed to understand young womens preferences for PrEP implants to inform optimal design. We developed a discrete choice experiment and surveyed 800 young women in Harare, Zimbabwe and Tshwane, South Africa between September-November 2020. Women aged 18-30 years who were nulliparous, postpartum, or exchanged sex for money, goods or shelter in prior year were eligible quotas were set for each subgroup. The DCE asked participants to choose between two hypothetical implants for HIV prevention in a series of nine questions. Implants were described by size, number of rods and insertion sites, duration (6-months, 1-year, 2-years), flexibility, and biodegradability. Random-parameters logit models estimated preference weights. Median age was 24 years (interquartile range 21-27). By design, 36% had used contraceptive implants. Duration of protection was most important feature, with strong preference for a 2-year over 6-month implant. In Zimbabwe, the number of rodsinsertion sites was second most important and half as important as duration. Nonetheless, to achieve an implant lasting 2-years, 74% were estimated to accept two rods, one in each arm. In South Africa, preference was for longer, flexible implants that required removal, although each of these attributes were one-third as important as duration. On average, biodegradability and size did not influence Zimbabwean womens choices. Contraceptive implant experience and parity did not influence relative importance of attributes. While duration of protection was a prominent attribute shaping womens choices for PrEP implants, other characteristics related to discreetness were relevant. Optimizing for longest dosing while also ensuring minimal detection of implant placement seemed most attractive to potential users.

A peer group intervention implemented by community volunteers increased HIV prevention knowledge.

HIV prevention knowledge levels are low in sub-Saharan Africa. In our efficacy study, the Mzake ndi Mzake (Friend-to-Friend hereafter Mzake) 6-session peer group intervention, delivered by health workers, improved HIV prevention knowledge and other outcomes in Malawi. To expand HIV prevention approaches, this implementation study tested whether the intervention remained effective when implemented by trained community volunteers. HIV prevention knowledge findings are presented. Using a stepped wedge design, three communities implemented the Mzake program sequentially in randomly assigned order. Repeated surveys assessed outcomes, and participants served as controls until they completed the program. At Time 2, Community 1 became the intervention group, and at Time 3, Communities 1 and 2 were the intervention group. HIV prevention knowledge, the primary outcome, was assessed through two indicators UNAIDS comprehensive knowledge (UNAIDS Knowledge), defined as correctly answering five HIV prevention questions (YesNo), and a 9-item HIVPMTCT Knowledge Index (number correct). Multivariate generalized estimating equation logistic regression (UNAIDS Knowledge) and mixed-effects regression models (HIVPMTCT Knowledge Index) were used to assess knowledge controlling for five sociodemographic factors. In bivariate analyses of UNAIDS Knowledge, more persons answered correctly in the intervention group than the control group at Time 2 (56.8% vs. 47.9%, p < 0.01), but the difference was not significant at Time 3. In logistic regression, there was a significant linear increase in the proportion who correctly answered all questions in the control group, but the increase was significantly higher in the intervention group (log-odds estimate 0.17, SE 0.06, p-value < 0.01). The HIVPMTCT Knowledge Index scores increased over time for both groups, but in the intervention group the increase was significantly higher than the control group (0.11 at Time 2 0.21 at Time 3). In youth and adult subsamples analyses, the intervention was highly effective in increasing knowledge for youth, but not for adults. This implementation study showed that Mzake was effective in increasing HIV prevention knowledge when delivered by community members. Community approaches offer an important strategy to increase HIV prevention in rural communities without burdening healthcare systems. ClinicalTrials.gov NCT02765659. Registered 06052016.

Assessing survival time of outpatients with cervical cancer at the university of Gondar referral hospital using the Bayesian approach.

Cervical cancer is the 4th most common cancer in women worldwide. as well as the 4th most common cause of cancer-related death. The main objective of this study was to identify factors that affect the survival time of outpatients with cervical cancer. A retrolective study including outpatients with cervical cancer was carried out in a hospital. To achieve the aim, 322 outpatients with cervical cancer were included in the study based on the data taken from the medical records of patients enrolled from May 15, 2018, to May 15, 2022, at the University of Gondar referral hospital, Gondar, Ethiopia. The Kaplan-Meier plots and log-rank test were used for the comparison of survival functions the Cox-PH model and Bayesian parametric survival models were used to analyze the survival times of outpatients with cervical cancer. Integrated nested Laplace approximation methods have been applied. Out of a total of 322 patients, 118 (36.6%) died as outpatients. The estimated median survival time for patients was 42 months. Using model selection criteria, the Bayesian log-normal accelerated failure time model was found to be appropriate. According to the results of this model, oral contraceptive use, HIV, stage, grade, co-morbid disease, history of abortion, weight, histology type, FIGO stage, radiation, chemotherapy, LVSI, metastatic number, regional nodes examined, and tumor size all have a significant impact on the survival time of outpatients with cervical cancer. The Bayesian log-normal accelerated failure time model accurately predicted the survival time of cervical cancer outpatients. The findings of this study suggested that reductions in weight, treatment, the presence of comorbid disease, the presence of HIV, squamous cell histology type, having a history of abortion, oral contraceptive use, a large tumor size, an increase in the International Federation of Gynecologists and Obstetricians stage, an increase in metastasis number, an increase in grade, positive regional nodes, lymphatic vascular space invasion, and late stages of cancer all shortened the survival time of cervical cancer outpatients.

A factorial experiment grounded in the multiphase optimization strategy to promote viral suppression among people who inject drugs on the Texas-Mexico border a study protocol.

People who inject drugs living with HIV (PWIDLH) suffer the lowest rates of HIV viral suppression due to episodic injection drug use and poor mental health coupled with poor retention in HIV care. Approximately 44% of PWIDLH along the US-Mexico border are retained in care and only 24% are virally suppressed. This underserved region faces a potential explosion of transmission of HIV due to highly prevalent injection drug use. This protocol describes an optimization trial to promote sustained viral suppression among Spanish-speaking Latinx PWIDLH. The multiphase optimization strategy (MOST) is an engineering-inspired framework for designing and building optimized interventions and guides this intervention. The primary aim is to conduct a 2 We are testing well-studied and available intervention components to support PWIDLH to reduce drug use and improve their mental health and engagement in HIV care. The intervention design will allow for a better understanding of how these components work in combination and can be optimized for the setting. This project was registered at clinicaltrials.gov (NCT05377463) on May 17th, 2022.

Upper respiratory tract mucosal immunity for SARS-CoV-2 vaccines.

SARS-CoV-2 vaccination significantly reduces morbidity and mortality, but has less impact on viral transmission rates, thus aiding viral evolution, and the longevity of vaccine-induced immunity rapidly declines. Immune responses in respiratory tract mucosal tissues are crucial for early control of infection, and can generate long-term antigen-specific protection with prompt recall responses. However, currently approved SARS-CoV-2 vaccines are not amenable to adequate respiratory mucosal delivery, particularly in the upper airways, which could account for the high vaccine breakthrough infection rates and limited duration of vaccine-mediated protection. In view of these drawbacks, we outline a strategy that has the potential to enhance both the efficacy and durability of existing SARS-CoV-2 vaccines, by inducing robust memory responses in the upper respiratory tract (URT) mucosa.

Prevalence of non-alcoholic fatty liver disease in a multicentre cohort of people living with HIV in Spain.

Non-alcoholic fatty liver disease (NAFLD) is one of the most important liver comorbidities in people living with HIV (PLWH). Factors that could lead to a higher prevalence of NAFLD or ease the onset of fibrosis are unclear. Cohort study of the Spanish HIV Research Network, which comprehends 46 hospitals and more than 15,000 PLWH. Primary objectives were to assess NAFLD prevalence and liver fibrosis according to hepatic steatosis index (HSI) and NAFLD fibrosis score, respectively. Factors associated with both were analysed. A total of 4798 PLWH were included of whom 1461 (30.5%) showed an HSI>36 these patients had higher risk for significant fibrosis (OR 1.91 95%CI 1.11-3.28). Factors associated with NAFLD were body mass index (OR 2.05 95%CI 1.94-2.16) and diabetes (OR 4.68 95%CI 2.17-10.08), while exposure to integrase strand transfer inhibitors showed a lower risk (OR 0.78 95%CI 0.62-0.97). In patients with HSI>36, being female (OR 7.33 95%CI 1.34-40), age (OR 1.22 95%CI 1.11-1.34), body mass index (OR 1.35 95%CI 1.18-1.54) and exposure to thymidine analogues (OR 75.4, 95%CI 6.9-823.5) were associated with a higher risk of significant fibrosis. However, exposure to non-nucleoside reverse transcriptase inhibitors (OR 0.12, 95%CI 0.02-0.89) and time of exposure to protease inhibitors (OR 0.97, 95%CI 0.95-1) showed a lower risk. NAFLD prevalence was high in our cohort. Patients exposed to INSTI showed a lower risk of NAFLD. In patients with hepatic steatosis, exposure to thymidine analogues had 75-fold more risk of significant fibrosis while exposure to NNRTIs reduced this risk.

The life and death of living systematic reviews a methodological survey.

The objectives of this study are to describe the characteristics of Living Systematic Reviews (LSRs) and to understand their life cycles. We conducted a comprehensive search up to April 2021 then selected articles and abstracted data in duplicate and independently. We undertook descriptive analyses and calculated delay in version update and delay since the last published version. We included 76 eligible LSRs with a total of 279 eligible versions. The majority of LSRs was from the clinical field (70%), was COVID-19 related (63%), and had a funding source specified (62%). The median number of versions per LSR was 2 (interquartile range (IQR) 1-4 range 1-19). The median and IQR for the ratio of the actual period of update to the planned period of update was 1.12 (0.81 1.71). Out of all reviews with a planned period of update and at least one update (N19), eight LSRs (42%) had a period since last published version greater than 3 times the planned period of update. No LSR included a retirement notice in their latest published version CONCLUSION While most LSR complied with the planned period of producing updates, a substantive proportion lagged since their last update.

Evaluation of plasma doravirine concentrations in patients with HIV-1 undergoing hemodialysis.

The pharmacokinetics of doravirine (DOR) have not been clarified in patients undergoing hemodialysis (HD). In this study, we evaluated the pharmacokinetics of DOR in four HIV-1-infected patients undergoing HD who were administered DOR. The participants were patients undergoing HD for end-stage renal disease and were administered DOR. DOR was administered once daily (one tablet of 100 mg), every evening. On days of HD treatment, DOR was administered after the end of the procedure. After administration of DOR for at least 1 week, the plasma DOR concentration was measured. The median plasma trough DOR concentration was 766.9 ngmL (range 509-1085 ngmL). The median DOR clearance by HD, DOR elimination rate, half-life (T

Modeling the effects of drugs of abuse on within-host dynamics of two HIV species.

Injection drug use is one of the most significant risk factors associated with contracting human immunodeficiency virus (HIV), and drug users infected with HIV suffer from a higher viral load and rapid disease progression. While replication of HIV may result in many mutant viruses that can escape recognition of the hosts immune response, the presence of morphine (a drug of abuse) can decrease the viral mutation rate and cellular immune responses. This study develops a mathematical model to explore the effects of morphine-altered mutation and cellular immune response on the within-host dynamics of two HIV species, a wild-type and a mutant. Our model predicts that the morphine-altered mutation rate and cellular immune response allow the wild-type virus to outcompete the mutant virus, resulting in a higher set point viral load and lower CD4 count. We also compute the basic reproduction numbers and show that the dominant species is determined by morphine concentration, with the mutant dominating below and the wild-type dominating above a threshold. Furthermore, we identified three biologically relevant equilibria, infection-free, mutant-only, and coexistence, which are completely characterized by the fitness cost of mutation, mutant escape rate, and morphine concentration.

The oropharynx of men using HIV pre-exposure prophylaxis is enriched with antibiotic resistance genes a cross-sectional observational metagenomic study.

Phenotypic studies have found high levels of antimicrobial resistance to cephalosporins, macrolides and fluoroquinolones in commensal Neisseria species in the oropharynx of men who have sex with men (MSM) using HIV pre-exposure prophylaxis (PrEP). These species include Neisseria subflava and Neisseria mucosa. This may represent a risk to pathogens like Neisseria gonorrhoeae which tend to take up antibiotic resistance genes (ARGs) from other bacteria. We aimed to explore to what extent the oropharyngeal resistome of MSM using PrEP differred from the general population. We collected oropharyngeal swabs from 32 individuals of the general population and from 64 MSM using PrEP. Thirty-two MSM had consumed antibiotics in the previous six months, whereas none of the other participants had. Samples underwent shotgun metagenomic sequencing. Sequencing reads were mapped against MEGARes 2.0 to estimate ARG abundance. ARG abundance was compared between groups by zero-inflated negative binomial regression. ARG abundance was significantly lower in the general population than in MSM (ratio 0·41, 95% CI 0·26 - 0·65). More specifically, this was the case for fluoroquinolones (0·33, 95% CI 0·15 - 0·69), macrolides (0·37, 95% CI 0·25 - 0·56), tetracyclines (0·41, 95% CI 0·25 - 0·69), and multi-drug efflux pumps (0·11, 95% CI 0·03 - 0·33), but not for beta-lactams (1·38, 95% CI 0·73 - 2·61). There were no significant differences in ARG abundance between MSM who had used antibiotics and those that had not. The resistome of MSM using PrEP is enriched with ARGs, independent of recent antibiotic use. Stewardship campaigns should aim to reduce antibiotic consumption in populations at high risk for STIs.

Effects of clinical, comorbid, and social determinants of health on brain ageing in people with and without HIV a retrospective case-control study.

Neuroimaging reveals structural brain changes linked with HIV infection and related neurocognitive disorders however, group-level comparisons between people with HIV and people without HIV do not account for within-group heterogeneity. The aim of this study was to quantify the effects of comorbidities such as cardiovascular disease and adverse social determinants of health on brain ageing in people with HIV and people without HIV. In this retrospective case-control study, people with HIV from Washington University in St Louis, MO, USA, and people without HIV identified through community organisations or the Research Participant Registry were clinically characterised and underwent 3-Tesla T In people with HIV (mean age 44·8 years SD 15·5 78% 296 of 379 male 69% 260 Black 78% 295 undetectable viral load), brain-age gap was associated with Framingham cardiovascular risk score (p0·0034), detectable viral load (>50 copies per mL p0·0023), and hepatitis C co-infection (p0·0065). After variable selection, the final model for people with HIV retained Framingham score, hepatitis C, and added unemployment (p0·0015). Educational achievement assayed by reading proficiency was linked with reduced brain-age gap (p0·016) for people without HIV but not for people with HIV, indicating a potential resilience factor. When people with HIV and people without HIV were modelled jointly, selection resulted in a model containing cardiovascular risk (p0·0039), hepatitis C (p0·037), Area Deprivation Index (p0·033), and unemployment (p0·00010). Male sex (p0·078) and alcohol use history (p0·090) were also included in the model but were not individually significant. Our findings indicate that comorbid and social determinants of health are associated with brain ageing in people with HIV, alongside traditional HIV metrics such as viral load and CD4 cell count, suggesting the need for a broadened clinical perspective on healthy ageing with HIV, with additional focus on comorbidities, lifestyle changes, and social factors. National Institute of Mental Health, National Institute of Nursing Research, and National Institute of Drug Abuse.

Atlas of the receptive anal sex experience among people with prostates.

Receptive anal intercourse (RAI) is commonly practiced among individuals of all sexual orientations. However, negative stigmatization by society and health care professionals leads to the underreporting or this practice. We sought to assess and describe the subjective role of the prostate as a pleasure center in participants with diverse RAI experiences. The secondary aim was to describe nonprostatic areas within the anorectal region that produce erotic sensation andor pain. The exploratory sequential multimethod study design included focus groups and semistructured interviews with 30 individuals with prostates who had engaged in RAI. We used graphic elicitation of natal male anatomy to enhance visualization and assess participant perspectives. The main outcome of interest was the identification of anatomic locations of erogenous sensation and pain during RAI. Among the participants (median age 38, range 24-77 years), most participants (90%) identified as cisgender male. Three major themes emerged within the motivations for RAI, including (1) deriving intrinsic pleasure, (2) providing both pleasure for a partner and a way to improve intimacyconnection, and (3) an inability to be the insertive partner due to physical or mental challenges. The data suggest that the anorectal region produces a variety of erogenous sensations which participants find pleasurable. Overall, 2 major areas of erogenous sensation occur along the anterior rectal wall and within the anus. Within the context of RAI, 2 distinct categories of pain emerged, including pain with insertion and pain at other times. Understanding where erogenous sensation originates for each individual may predict sexual functioning after various surgical interventions. Timing and location of pain may aid in further characterizing anodyspareunia. Our study utilized a sequential design (from focus groups to interviews) with diverse RAI experiences, especially regarding age, geographic location, and prostate pathology. We included individuals of diverse gender identities, but too few to evaluate these groups independently from cisgender men. People with prostates experience pleasure in multiple areas during RAI. Contrary to some lay literature, the prostate region is not the subjective pleasure center for all individuals. Timing and location of pain during RAI may inform areas for intervention. Providing a language for pleasure and pain during RAI may improve communication between not only sexual partners but also clinicians and patients.