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Investigating the impact of stigma, accessibility and confidentiality on STISTDHIV self-testing among college students in the USA protocol for a scoping review.

In 2019, there were 2.5 million reported cases of chlamydia, gonorrhoea and syphilis. The Centers for Disease Control and Prevention reported in the USA, young people aged 15-24 made up 61% and 42% of chlamydia and gonorrhoea cases, respectively. Moreover, the highest rates of sexually transmitted infections (STIs) were reported among college-aged students. In this paper, we outline our protocol to systematically review the published literature on, the use of STIHIV self-test kits, increasing STIHIV testing uptake, and stigma, access and confidentiality issues, among young adult college students in the USA. This scoping review will be conducted and reported according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. We will search electronic databases, OVID Medline, OVID Embase, Web of Science, Cochrane Library, PubMed and CINAHL, for articles published in English from inception to the present. We will search other alternative sources such as ProQuest, Google Scholar and Google to identify grey literature. A two-step process will be used to identify eligible studies based on the defined inclusion criteria. First, the title and abstract of identified articles will be screened for possible inclusion. Second, full-text articles of relevant studies will be retrieved and screened for inclusion. Both screening steps will be done by two people independently. Finally, data will be extracted by two researchers working independently. Any arising disagreements will be resolved by consensus or by a third author. This study is a scoping review of the literature. Therefore, ethics approval is not required. Our plan for the dissemination of findings includes peer-reviewed manuscripts, conferences and webinars.

Living in Stealth A Grounded Theory Study of Transgender Womens Barriers to HIV-Prevention Services and Interventions.

The Dimensions of Desire Among Gay, Bisexual, and Other Men Who Have Sex With Men (gbMSM) An Evolutionary Concept Analysis.

Cost-effectiveness of tuberculosis infection prevention and control interventions in South African clinics a model-based economic evaluation informed by complexity science methods.

Nosocomial A set of TB IPC interventions was codesigned with local stakeholders using system dynamics modelling techniques that addressed both core activities and enabling actions to support implementation. An economic evaluation of these interventions was conducted at two clinics in KwaZulu-Natal, employing agent-based models of All intervention scenarios modelled, inclusive of the relevant enablers, cost less than US$200 per disability-adjusted life-year (DALY) averted and were very cost-effective in comparison to South Africas opportunity cost-based threshold (US$3200 per DALY averted). Two interventions, building modifications to improve ventilation and maximising use of the existing Central Chronic Medicines Dispensing and Distribution system to reduce the number of clinic attendees, were found to be cost saving over the 10-year model time horizon. Incremental cost-effectiveness ratios were sensitive to assumptions on baseline clinic ventilation rates, the prevalence of infectious TB in clinic attendees and future HIV incidence but remained highly cost-effective under all uncertainty analysis scenarios. TB IPC interventions in clinics, including the enabling actions to ensure their feasibility, afford very good value for money and should be prioritised for implementation within the South African health system.

Alcohol-focused and transdiagnostic treatments for unhealthy alcohol use among adults with HIV in Zambia A 3-arm randomized controlled trial.

Clinical and quality of life outcomes in people living with human immunodeficiency virus (PLWH) are undermined by unhealthy alcohol use (UAU), which is highly prevalent in this population and is often complicated by mental health (MH) or other substance use (SU) comorbidity. In sub-Saharan Africa, evidence-based and implementable treatment options for people with HIV and UAU are needed. We are conducting a hybrid clinical effectiveness-implementation trial at three public-sector HIV clinics in Lusaka, Zambia. Adults with HIV, who report UAU, and have suboptimal HIV clinical outcomes, will be randomized to one of three arms an alcohol-focused brief intervention (BI), the BI with additional referral to a transdiagnostic cognitive behavioral therapy (Common Elements Treatment Approach CETA), or standard of care. The BI and CETA will be provided by HIV peer counselors, a common cadre of lay health worker in Zambia. Clinical outcomes will include HIV viral suppression, alcohol use, assessed by audio computer-assisted self-interview (ACASI) and direct alcohol biomarkers, Phophatidylethanol and Ethyl glucuronide, and comorbid MH and other SU. A range of implementation outcomes including cost effectiveness will also be analyzed. Hybrid and 3-arm trial design features facilitate the integrated evaluation of both brief, highly implementable, and more intensive, less implementable, treatment options for UAU among PLWH in sub-Saharan Africa. Use of ACASI and alcohol biomarkers will strengthen understanding of treatment effects.

Missed Opportunities for Prevention Prevalence and Incidence of HIV and HCV Diagnoses Among a Cohort of Individuals Discharged from an Urban Hospital with Injection Drug Related Diagnoses, 2012-2019.

Risk for HIV and hepatitis C virus (HCV) infections have increased due to the on-going opioid epidemic and unsafe injection practices. We estimated prevalence and incidence of HIV and HCV diagnoses among people who inject drugs (PWID) from hospital-based clinical encounters. We linked clinical encounters at an Atlanta hospital during 2012-2018 with state HIV and HCV surveillance records to examine prevalence of infections at discharge and incidence of infections post-clinical encounter. At discharge, 32.9% and 28.6% of patients with IDU-related clinical encounters had an HIV or HCV diagnosis, respectively. HIV and HCV diagnoses at time of discharge were mostly among 40-64 year-old patients, males, and BlackAfrican Americans. Post-clinical encounter, 3.8% of patients were later diagnosed with HIV, and 16.5% were later diagnosed with HCV, translating to incidence rates of 9.3 per 1,000 person-years and 41.5 per 1,000 person-years, respectively. The majority of HIV and HCV diagnoses post-clinical encounter occurred among BlackAfrican Americans and males. Of patients with HIV and HCV diagnoses post-clinical encounter, 27.3% and 11.9% had been tested during their clinical encounter, respectively. Targeted interventions for HIVHCV prevention, screening, diagnosis and linkage to treatment are needed to reduce incidence of new infections among PWID.

Pro-inflammatory and pro-resolving lipid mediators of inflammation in HIV effect of aspirin intervention.

Persons with HIV (PWH) have an increased risk of cardiovascular disease (CVD) compared to HIV-seronegative individuals (SN). Inflammation contributes to this risk but the role of lipid mediators, with central roles in inflammation, in HIV infection remain to be established further aspirin reduces CVD risk in the general population through production of some of these anti-inflammatory lipid mediators, but they have not been studied in PWH. We evaluated the relationship between plasma lipid mediators (i.e. 50 lipid mediators including classic eicosanoids and specialized pro-resolving mediators (SPMs)) and HIV status and the impact of aspirin in PWH on regulating these autacoids. Plasma samples were obtained from 110 PWH receiving antiretroviral therapy (ART) from a randomized trial of aspirin (ACTG-A5331) and 107 matched SN samples (MACS-WIHS Combined Cohort). PWH had lower levels of arachidonic acid-derived pro-inflammatory prostaglandins (PGs PGE Together these observations demonstrate that plasma lipid mediators profiles, some with links to systemic inflammation and CVD risk, become altered in PWH. Furthermore, aspirin intervention did not increase levels of aspirin-triggered pro-resolving lipid mediators, consistent with other reports of an impaired aspirin response in PWH. NIH.

Structure-directed linker optimization of novel HEPTs as non-nucleoside inhibitors of HIV-1 reverse transcriptase.

1-(2-Hydroxyethoxy)methyl-6-(phenylthio)thymines (HEPTs) have been previously described as an important class of HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs). In our continuously pursuing HEPT optimization efforts, a series of novel HEPTs, featuring -C(OH)CH

Mortality inequalities of Black adults in Canada.

Mortality rates in Canada have been shown to vary by population group (e.g., Indigenous peoples, immigrants) and social economic status (e.g., income levels). Mortality patterns for some groups, including Black individuals, are not as well known. The objective of this study was to assess cause-specific mortality for Black adults living in Canada. Mortality inequalities between Black and White cohort members were estimated by sex using Cox proportional hazard models, based on data from the 2001, 2006 and 2011 Canadian Census Health and Environment Cohorts (CanCHECs). The CanCHEC cycles were combined and followed for mortality between Census Day and December 31, 2016 or 2019, resulting in a follow-up period of 15.6, 13.6 or 8.6 years, depending on the CanCHEC cycle. Ischemic heart disease mortality was the leading cause of death among adult Black males (12.9%) and females (9.8%), as it is for adult White males (16.4%) and females (12.4%). Despite reduced risk of all-cause mortality among Black males and females, compared with White cohort members, there was notable increased risk for some cause-specific mortality. For instance, in the age-adjusted model, among the 25 causes of death examined, Black males had an increased risk of dying from four causes (HIVAIDS, prostate cancer, diabetes mellitus and cerebrovascular disease), compared with White males. Similarly, Black females were at an increased risk for 6 causes of death (HIVAIDS, stomach cancer, corpus uteri cancer, lymphomas and multiple myeloma, diabetes mellitus, and endocrine disorders) out of the 27 causes of death examined. These relative increased risks persisted for most causes of death after adjustment for differences in important social determinants of health. Results showed substantial variability in the risk of dying by cause of death between Black and White cohort members. An important step in reducing health inequities is the routine identification and surveillance of different health outcomes by population groups. This study helps fill that information gap.

Blood-borne infections and pregnancies among women attending a sexual violence assistance center in Brazil A 10-year retrospective study.

Sexually transmitted infections (STI) and pregnancy can be consequences of sexual violence. In Brazil, around 50% of women victims of sexual violence do not undergo STI prophylaxis or emergency contraception. To analyze socio-demographic and epidemiological profile, frequency of procedures performed, frequency of blood-borne infections (BBI), pregnancy, and legal abortion in women assisted by a sexual violence assistance center. This 10-year retrospective cohort study (2010-2019) describes the socio-demographic and epidemiological profile and frequencies of clinical procedures, BBI, pregnancies, and legal abortions in 915 women assisted in a sexual violence assistance center in Brazil. We extracted data from the medical records and used descriptive statistics and chi-square and logistic regression. A total of 93.3% (842915) were residents in the Metropolitan Area of the capital, 80,83% (733915) were brown-skinned or white, 42.4% (388915) were adolescents (12-17 years old), 80.4% (736915) were single, most had no children, average of 1.8 (±1.0 DP) children. About one-third (313915) had not had previous sexual intercourse, 1.6% (10653) were pregnant. Rape predominated with 92.0% (841915), of which 51.5% (471915) involved a known or related aggressor, mostly an acquaintance, followed by a stepfather or father. Recurrent cases were 24.0% (227915). 42.6% (390915) were attended within 72 hours and received STI prophylaxis 43.4% (392904) emergency contraception 38.6% (349904) blood collection 71.6% (647904). Prevalence syphilis 0.3% (2653) hepatitis B 0.2% (1653) pregnancy 1.6% (10653). Incidences syphilis 1.1% (7633) hepatitis B 0.8% (5633) hepatitis C 0.6% (4633) pregnancy 27.2% (172633). There were no HIV cases. Trichomoniasis at 1.9% (2108), HPV-induced cytological lesions at 4.7% (5108), and bacterial vaginosis at 20.0% (21108) were found on cervicovaginal samples. There were 129 legal abortions. The socio-demographic aspects and the characteristics of the aggressions in the studied population are like those described in the Brazilian national database, including the remarkable number of adolescents. STI prophylaxis and emergency contraception were performed in less than half of the women. The incidence of pregnancy was higher among those women reporting firearms threats and lower among those receiving STI prophylaxis. The frequency of legal abortion was higher than in national data. Public policies ensuring access to sexual and reproductive health rights and strategies to improve the quality of care for women victims of sexual violence and education improvement may decrease vulnerability to STI and unintended pregnancies.

Genomic profiling of HIV-1 integration in microglia cells links viral integration to the topologically associated domains.

HIV-1 encounters the hierarchically organized host chromatin to stably integrate and persist in anatomically distinct latent reservoirs. The contribution of genome organization in HIV-1 infection has been largely understudied across different HIV-1 targets. Here, we determine HIV-1 integration sites (ISs), associate them with chromatin and expression signatures at different genomic scales in a microglia cell model, and profile them together with the primary T cell reservoir. HIV-1 insertions into introns of actively transcribed genes with IS hotspots in genic and super-enhancers, characteristic of blood cells, are maintained in the microglia cell model. Genome organization analysis reveals dynamic CCCTC-binding factor (CTCF) clusters in cells with active and repressed HIV-1 transcription, whereas CTCF removal impairs viral integration. We identify CTCF-enriched topologically associated domain (TAD) boundaries with signatures of transcriptionally active chromatin as HIV-1 integration determinants in microglia and CD4

A Standardized Approach for Collection of Objective Data to Support Outcome Determination for Late-Phase TB Trials.

We developed a standardized method, Possible poor treatment response (PPTR), to help ascertain efficacy endpoints in Study S31A5349 (NCT02410772), an open-label trial comparing two 4-month rifapentine-based regimens with a standard 6-month regimen for the treatment of pulmonary TB. We describe the use of the PPTR process and evaluate whether the goals of minimizing bias in efficacy endpoint assessment and attainment of relevant data to determine outcome for all participants were achieved. A PPTR event was defined as the occurrence of one or more pre-specified triggers. Each PPTR required initiation of a standardized evaluation process that included obtaining multiple sputum samples for microbiology. Among 2,343 participants with culture-confirmed drug-susceptible TB, 454 individuals (19.4%) had a total of 534 individual PPTR events, of which 76.6% were microbiological (positive smear or culture at or after 17 weeks). At least one PPTR event was experienced by 92.4% (133 of 144) of participants with TB-related unfavorable outcome, and between 13.8 and 14.7% of participants with favorable and not assessable outcomes. 75% of participants with TB-related unfavorable outcomes had microbiological confirmation of failure to achieve disease-free cure. Standardized methodologies, such as our PPTR approach, could facilitate unbiased efficacy outcome determinations, improve discrimination between outcomes that are related and unrelated to regimen efficacy, and enhance the ability to conduct pooled analyses of contemporary trials. Clinical trial registration available at www. gov, ID NCT02410772.

IL-18 and IL-3 in Extracellular Vesicles Biomarkers for Durable Elite Control of HIV-1.

Plasma extracellular vesicle (EV)-associated cytokines were quantified in people with HIV (PWH) with different virological control status, including elite controllers (EC) who maintain persistent control (PC) or not (TC). Cytokine signatures and pathways were determined for each group. Median EV-associated cytokine levels were higher among PWH than HIV-uninfected. EC showed the highest levels of EV-associated cytokines among PWH with PC levels higher than TC levels. IL-18 levels best distinguished PWH from uninfected controls, and EC from ART-treated, and IL-3 distinguished PC from TC. The role of EV-cytokines in intercellular communication and endogenous control of HIV expression should be investigated further.

Seroprevalence of Antibodies to SARS-CoV-2 in Rural Households in Eastern Uganda, 2020-2022.

Estimating the true burden of SARS-CoV-2 infection has been difficult in sub-Saharan Africa owing to asymptomatic infections and inadequate testing capacity. Antibody responses from serologic surveys can provide an estimate of SARS-CoV-2 exposure at the population level. To estimate SARS-CoV-2 seroprevalence, attack rates, and reinfection in eastern Uganda using serologic surveillance from 2020 to early 2022. This cohort study was conducted in the Tororo and Busia districts of eastern Uganda. Plasma samples from participants in the Program for Resistance, Immunology, Surveillance, and Modeling of Malaria in Uganda Border Cohort were obtained at 4 sampling intervals October to November 2020, March to April 2021, August to September 2021, and February to March 2022. Each participant contributed up to 4 time points for SARS-CoV-2 serology, with almost half of all participants contributing at all 4 time points, and almost 90% contributing at 3 or 4 time points. Information on SARS-CoV-2 vaccination status was collected from participants, with the earliest reported vaccinations in the cohort occurring in May 2021. The main outcomes of this study were antibody responses to the SARS-CoV-2 spike protein as measured with a bead-based serologic assay. Individual-level outcomes were aggregated to population-level SARS-CoV-2 seroprevalence, attack rates, and boosting rates. Estimates were weighted by the local age distribution according to census data. A total of 1483 samples from 441 participants living in 76 households were tested. Of the 441 participants, 245 (55.6%) were female, and their mean (SD) age was 16.04 (16.04) years. By the end of the Delta wave and before widespread vaccination, adjusted SARS-CoV-2 seroprevalence was 67.7% (95% credible interval CrI, 62.5%-72.6%) in the study population. During the subsequent Omicron wave, 84.8% (95% CrI, 67.9%-93.7%) of unvaccinated, previously seronegative individuals were infected for the first time, and 50.8% (95% CrI, 40.6%-59.7%) of unvaccinated, already seropositive individuals were likely reinfected, leading to an overall seropositivity of 96.0% (95% CrI, 93.4%-97.9%) in this population. These results suggest a lower probability of reinfection in individuals with higher preexisting antibody levels. There was evidence of household clustering of SARS-CoV-2 seroconversion. No significant associations were found between SARS-CoV-2 seroconversion and gender, household size, or recent Plasmodium falciparum malaria exposure. In this cohort study in a rural population in eastern Uganda, there was evidence of very high SARS-CoV-2 infection rates throughout the pandemic inconsistent with national level case data and high reinfection rates during the Omicron wave.

Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium analysis from a randomised placebo-controlled trial.

HIV-associated neurocognitive disorders (HAND) persist in the era of antiretroviral therapy (ART). Thus, ART does not completely halt or reverse the pathological processes behind HAND. Adjuvant mitigating treatments are, therefore, prudent. Lithium treatment is known to promote neuronal brain-derived neurotrophic factors (BDNF). Lithium is also an inhibitor of glycogen synthase kinase-3 beta (GSK-3-β). We analyzed biomarkers obtained from participants in a randomized placebo-controlled trial of lithium in ART-treated individuals with moderate or severe HAND. We assayed markers at baseline and 24 weeks across several pathways hypothesized to be affected by HIV, inflammation, or degeneration. Investigated biomarkers included dopamine, BDNF, neurofilament light chain, and CD8 lymphocyte activation (CD38 HLADR ). Alzheimers Disease (AD) biomarkers included soluble amyloid precursor protein alpha and beta (sAPPαβ), Aβ38, 40, 42, and ten other biomarkers validated as predictors of mild cognitive impairment and progression in previous studies. These include apolipoprotein C3, pre-albumin, α1-acid glycoprotein, α1-antitrypsin, PEDF, CC4, ICAM-1, RANTES, clusterin, and cystatin c. We recruited 61 participants (placebo 31 lithium 30). The age baseline mean was 40 (± 8.35) years and the median CD4 T-cell count was 498 (IQR 389-651) cellsμL. Biomarker concentrations between groups did not differ at baseline. However, both groups blood dopamine levels decreased significantly after 24 weeks (adj. p < 002). No other marker was significantly different between groups, and we concluded that lithium did not confer neuroprotection following 24 weeks of treatment. However, the study was limited in duration and sample size.

Classical fever of unknown origin in 21 countries with different economic development an international ID-IRI study.

Fever of unknown origin (FUO) is a serious challenge for physicians. The aim of the present study was to consider epidemiology and dynamics of FUO in countries with different economic development. The data of FUO patients hospitalizedfollowed between 1st July 2016 and 1st July 2021 were collected retrospectively and submitted from referral centers in 21 countries through ID-IRI clinical research platform. The countries were categorized into developing (low-income (LI) and lower middle-income (LMI) economies) and developed countries (upper middle-income (UMI) and high-income (HI) economies). This research included 788 patients. FUO diagnoses were as follows infections (51.6% n 407), neoplasms (11.4%, n 90), collagen vascular disorders (9.3%, n 73), undiagnosed (20.1%, n 158), miscellaneous diseases (7.7%, n 60). The most common infections were tuberculosis (n 45, 5.7%), brucellosis (n 39, 4.9%), rickettsiosis (n 23, 2.9%), HIV infection (n 20, 2.5%), and typhoid fever (n 13, 1.6%). Cardiovascular infections (n 56, 7.1%) were the most common infectious syndromes. Only collagen vascular disorders were reported significantly more from developed countries (RR 2.00, 95% CI 1.19-3.38). FUO had similar characteristics in LILMI and UMIHI countries including the portion of undiagnosed cases (OR, 95% CI 0.87 (0.65-1.15)), death attributed to FUO (RR 0.87, 95% CI 0.65-1.15, p-value 0.3355), and the mean duration until diagnosis (p 0.9663). Various aspects of FUO cannot be determined by the economic development solely. Other development indices can be considered in future analyses. Physicians in different countries should be equally prepared for FUO patients.

Adherence to antiretroviral therapy by people living with HIVAIDS in Florianópolis, Santa Catarina State, Brazil.

Adherence to antiretroviral therapy (ART) is essential to control HIV infections and avoid clinical complications and the development of resistant HIV strains. Several Brazilian municipalities have committed themselves to the 90-90-90 target, which aims at diagnosing 90% of HIVAIDS cases, treating 90% of them, and virally suppressing 90% of them. However, only three Brazilian studies have assessed adherence to ART from secondary dispensing data. This study aimed to estimate the prevalence of adherence to treatment in the Municipality of Florianópolis, Santa Catarina State, Brazil, examining its association with demographic, health access, and clinical characteristics. A cross-sectional study was conducted using secondary national data from electronic medical records and Medication Logistic Control System (SICLOM) and Laboratory Test Control System (SISCEL) regarding people living with HIVAIDS in the municipality from April 2020 to March 2021. We found an about 85% prevalence of adherence to ART. White men with follow-ups both in primary and secondary care showed greater adherence to treatment. Age and number of consultations directly related to adherence. Decentralizing care for users living with HIVAIDS is the way to more comprehensive care but technical and ethical challenges still require solutions. Professional training, correct network referrals, and attention to confidentiality issues must be reinforced to expand treatment adherence. A adesão à terapia antirretroviral (TARV) é fundamental para obter o controle da infecção por HIV, evitando complicações clínicas e o desenvolvimento de cepas de HIV resistentes. Vários municípios brasileiros estão comprometidos com a meta 90-90-90, que prevê que 90% dos casos de HIVaids sejam diagnosticados, que 90% destes estejam em tratamento e, destes, 90% alcancem a supressão viral. Entretanto, existem apenas três estudos brasileiros que avaliam a adesão à TARV a partir de dados secundários de dispensação. Este estudo objetivou estimar a prevalência de adesão ao tratamento no Município de Florianópolis, Santa Catarina, Brasil, examinando sua associação com aspectos demográficos, de utilização de saúde e características clínicas. Realizou-se um estudo transversal com o uso de dados secundários do prontuário eletrônico e dados nacionais, dos Sistema de Controle Logístico de Medicamentos (SICLOM) e Sistema de Controle de Exames Laboratoriais (SISCEL), de pessoas vivendo com HIVaids no município de abril de 2020 a março de 2021. A prevalência de adesão à TARV foi de cerca de 85%. Pessoas brancas, do sexo masculino, que tinham acompanhamento tanto na atenção primária à saúde (APS) quanto na atenção secundária tinham maior adesão ao tratamento. A idade e o número de consultas apresentaram associação direta com adesão à TARV. O processo de descentralização do cuidado ao usuário vivendo com HIVaids é o caminho para uma assistência mais integral, porém desafios técnicos e éticos ainda precisam ser enfrentados. A qualificação profissional, o correto referenciamento com articulação em rede e a atenção às questões de sigilo e confidencialidade precisam ser reforçadas de forma a ampliar a adesão ao tratamento. La adherencia a la terapia antirretroviral (TARV) es fundamental para controlar la infección por VIH, evitando complicaciones clínicas y el desarrollo de cepas de VIH resistentes. Varios municipios brasileños están comprometidos con la meta 90-90-90, que estima el diagnóstico del 90% de los casos de VIHSIDA, que el 90% de estos reciban tratamiento y, de estos, el 90% logran llegar a la supresión viral. Sin embargo, solo hay tres estudios brasileños que evalúan la adherencia al TARV con base en datos secundarios sobre la dispensación. Este estudio tuvo por objetivo estimar la prevalencia de adherencia al tratamiento en la ciudad de Florianópolis, Santa Catarina, Brasil y su asociación con aspectos demográficos, uso de la salud y características clínicas. Se realizó un estudio transversal con los datos secundarios de la historia clínica electrónica y los datos nacionales del Sistema de Control Logístico de Medicamentos (SICLOM) y Sistema de Control de Pruebas de Laboratorio (SISCEL) de las personas que viven con VIHSIDA en ese municipio en el período de abril de 2020 a marzo de 2021. La prevalencia de adherencia al TARV fue casi del 85%. Las personas de raza blanca, del sexo masculino, que recibían seguimiento en la atención primaria o en la atención secundaria tuvieron mayor adherencia al tratamiento. La edad y el número de consultas se asociaron directamente con la adherencia al TARV. El proceso de descentralización de la atención a los usuarios que viven con VIHSIDA y sida es la forma de brindar una atención más integral, pero aún se deben enfrentar desafíos técnicos y éticos. Es necesario mejorar la calificación profesional, la correcta derivación con articulación en red y tener cuidado al secreto y la confidencialidad para que se intensifique aún más la adherencia al tratamiento.

Sputum Microbiome and Chronic Obstructive Pulmonary Disease in a Rural Ugandan Cohort of Well-Controlled HIV Infection.

Sub-Saharan Africa has increased morbidity and mortality related to chronic obstructive pulmonary disease (COPD). COPD among people living with HIV (PLWH) has not been well studied in this region, where HIVAIDS is endemic. Increasing evidence suggests that respiratory microbial composition plays a role in COPD severity. Therefore, we aimed to investigate microbiome patterns and associations among PLWH with COPD in Sub-Saharan Africa. We conducted a cross-sectional study of 200 adults stratified by HIV and COPD in rural Uganda. Induced sputum samples were collected as an easy-to-obtain proxy for the lower respiratory tract microbiota. We performed 16S rRNA gene sequencing and used PICRUSt2 (version 2.2.3) to infer the functional profiles of the microbial community. We used a statistical tool to detect changes in specific taxa that searches and adjusts for confounding factors such as antiretroviral therapy (ART), age, sex, and other participant characteristics. We could cluster the microbial community into three community types whose distribution was shown to be significantly impacted by HIV. Some genera, e.g.,

Rare Presentation of Umbilical Condyloma.

Syphilis is associated with 3 stages of infection-primary, secondary, and tertiary-each with their own associated clinical findings. Secondary syphilis manifests with condyloma lata and other cutaneous findings, and typically occurs several months after the initial infection. Condyloma lata are primarily found in the genital area, but may also be found in other locations such as the umbilicus, axilla, and neck. This brief report describes an umbilical condyloma lata discovered in a patient with secondary syphilis and HIV co-infection and discusses surgical excision and fulguration as an option for definitive management.

Clinical Characteristics and Outcomes Among People Living With HIV Undergoing Percutaneous Coronary Intervention Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

Background Clinical characteristics and outcomes in people living with HIV (PLWH) undergoing percutaneous coronary intervention (PCI) remain poorly described. We sought to compare real-world treatment of coronary artery disease, as well as patient and procedural factors and outcomes after PCI between PLWH and uninfected controls. Methods and Results We utilized procedural registry data from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program between January 1, 2009 and December 31, 2019 to analyze patients with obstructive coronary artery disease on angiography. In the PCI subgroup, we used inverse probability of treatment weighting and applied Cox proportional hazards to evaluate the association of HIV serostatus with outcomes, including all-cause mortality at 5 years. Among 184 310 patients with obstructive coronary artery disease, treatment strategy was similar between PLWH and controls-35.7% versus 34.2% PCI, 13.6% versus 15% coronary artery bypass grafting, and 50.7% versus 50.8% medical therapy. The PCI cohort consisted of 546 (0.9%) PLWH and 56 811 (99.1%) controls. PLWH undergoing PCI had well-controlled HIV disease, and compared with controls, were younger, more likely to be Black, had fewer traditional risk factors, more acute coronary syndrome, less extensive coronary artery disease, and similar types of stents and P2Y12 therapy. However, PLWH experienced worse survival as early as 6 months post-PCI, which persisted over time and amounted to a 21% increased mortality risk by 5 years (hazard ratio, 1.21 95% CI, 1.03-1.42

SARS-CoV-2 live virus neutralization after four COVID-19 vaccine doses in people with HIV receiving suppressive ART.

Limited data exist regarding the immune benefits of fourth COVID-19 vaccine doses in people with HIV (PWH) receiving ART, particularly now that most have experienced a SARS-CoV-2 infection. We quantified wild-type (WT)-, Omicron-BA.5- and Omicron-BQ.1-specific neutralization up to one month postfourth COVID-19 vaccine dose in 63 (19 SARS-CoV-2-naive and 44 SARS-CoV-2-experienced) PWH. Longitudinal observational cohort. Quantification of wild-type (WT)-, Omicron-BA.5- and Omicron-BQ.1-specific neutralization using live virus assays. Participants received monovalent (44%) and bivalent (56%) mRNA fourth doses. In COVID-19-naive PWH, fourth doses enhanced WT- and Omicron-BA.5-specific neutralization modestly above three-dose levels (P 0.1). In COVID-19-experienced PWH, fourth doses enhanced WT-specific neutralization modestly (P 0.1) and BA.5-specific neutralization substantially (P 0.002). Consistent with humoral benefits of hybrid immunity, COVID-19-experienced PWH exhibited the highest neutralization postfourth dose, where those with Omicron-era infections displayed higher WT-specific (P 0.04) but similar BA.5- and BQ.1-specific neutralization than those with pre-Omicron-era infections. Nevertheless, BA.5-specific neutralization was significantly below WT in everyone regardless of COVID-19 experience, with BQ.1-specific neutralization lower still (both P < 0.0001). In multivariable analyses, fourth dose valency did not affect neutralization magnitude. Rather, an mRNA-1273 fourth dose (versus a BNT162b2 one) was the strongest correlate of WT-specific neutralization, while prior COVID-19, regardless of pandemic era, was the strongest correlate of BA.5 and BQ.1-specific neutralization postfourth dose. Fourth COVID-19 vaccine doses, irrespective of valency, benefit PWH regardless of prior SARS-CoV-2 infection. Results support recommendations that all adults receive a fourth COVID-19 vaccine dose within 6 months of their third (or their most recent SARS-CoV-2 infection).

Pharmacokinetics, Safety, and Bioequivalence of 2 LopinavirRitonavir (20050 mg) Tablets in Healthy Chinese Volunteers Effect of Food on Absorption.

Lopinavirritonavir is an important protease inhibitor for treating HIV-1 infection in patients aged >2 years in combination with other antiretrovirals. The antiviral activity of lopinavirritonavir in vivo is mainly derived from lopinavir, while ritonavir improves the bioavailability of lopinavir. This study compared the bioequivalence and safety of 2 lopinavirritonavir (20050 mg) formulations under fasted and fed conditions in healthy Chinese volunteers and compared the pharmacokinetic parameters of lopinavir and ritonavir. A randomized, open-label, single-dose, 4-period, crossover bioequivalence was conducted in 72 subjects under fasted and fed conditions. Lopinavir and ritonavir plasma concentrations were analyzed using validated liquid chromatography with tandem mass spectrometry. Noncompartmental analysis was used to evaluate pharmacokinetic parameters. The 90% confidence intervals of testreference geometric mean ratio for lopinavir and ritonavir area under the plasma concentration-time curve and maximum drug concentration meets the bioequivalence criteria based on the average bioequivalence method. A high-fat meal delayed the time to the maximum concentration of lopinavir and ritonavir. Therefore, these formulations were bioequivalent in healthy Chinese volunteers under fasting and fed conditions. Moreover, adverse events were more frequent in the fed state, but all were mild.

CRISPR-Cas9 editing of a TNPO3 mutation in a muscle cell model of limb-girdle muscular dystrophy type D2.

A single-nucleotide deletion in the stop codon of the nuclear import receptor transportin-3 (TNPO3), also involved in human immunodeficiency virus type 1 (HIV-1) infection, causes the ultrarare autosomal dominant disease limb-girdle muscular dystrophy D2 (LGMDD2) by extending the wild-type protein. Here, we generated a patient-derived

Queer collective memory during the time of COVID Timelessness, isolation, and resilience in the United Kingdom.

Oral history collections both rely on and preserve community memories, and are of importance for understanding marginalized communities, particularly when they privilege minority voices. This article draws from original, video-based oral histories conducted for the United Kingdoms national LGBTQ (lesbian, gay, bisexual, transgender, queerquestioning, and others) museum, Queer Britain, focusing on an ongoing collection of oral histories organized around experiences related to the COVID pandemic. In order to protect the health of those interviewed and the interviewers, the researchers used virtual meeting software to record video interviews and utilized qualitative software to expand and support interview analysis. Specific oral history methodologies and concepts are explored, and museum studies content is briefly discussed, specifically as it relates to museums of marginalized people. Themes explored include isolation and timelessness, the impact of the pandemic on diverse LGBTQ communities, and HIVAIDS.

Ocular Jarisch-Herxheimer Reaction in the Treatment of Ocular Syphilis A Case Report and Review of the Literature.

Jarisch-Herxheimer reaction (JHR) is a transient clinical phenomenon in patients with syphilis who receive antibiotic treatment. A 31-year-old man with an underlying HIV infection presented with worsening vision in the right eye two days after being treated with oral doxycycline for presumed left-eye neuroretinitis. Prior history revealed two episodes of penile discharge and ulcers that were not investigated. Examination showed bilateral optic disc swelling with right eye placoid chorioretinitis around the macula. Optical coherence tomography (OCT) demonstrated right macular edema and left macular thinning. Blood investigations confirmed syphilis infection. Subsequently, the patient was scheduled for a contrasted brain CT with oral steroid coverage due to underlying allergies. His vision incidentally improved soon after the short course of steroids. Repeated OCT demonstrated marked improvement of right macular edema, which we believe was secondary to JHR initiated by the earlier doxycycline treatment. Following oral steroid addition, improvement in vision and ocular findings were seen. At six-month post-treatment, there was right macular atrophy as a sequela of the macular edema. Ophthalmologists should be aware of ocular-related JHR complications, particularly in potentiating macular atrophy following macular edema upon initiating antibiotic treatment in syphilitic disease.

Osteoradionecrosis After Mandibulotomy and Marginal Mandibulectomy in Patients With Oral Cancer.

Objectives Osteoradionecrosis is one of the most severe complications in patients with head and neck cancer, which is characterized by persistent exposed and devitalized bone without proper healing after radiation. The extent to which mandibulotomy and marginal mandibulectomy influence the occurrence of osteoradionecrosis remains unclear. This study evaluated the incidence and risk factors for developing osteoradionecrosis of the mandible after oral cancer treatments. Methods A retrospective study was performed to analyze medical records of patients who underwent surgery and postoperative radiotherapy for oral cancers from 2009 to 2019 at a tertiary care hospital. Patient characteristics, incidence, and risk factors for developing osteoradionecrosis were reviewed. Comparisons between continuous and categorical data were performed using t-test and Chi-squared test. Cox regression analysis was used to assess the association between factors and the development of osteoradionecrosis. Results Among the 61 patients included in the study, osteoradionecrosis of the mandible occurred in 9 of 32 (28.1%) patients who underwent mandibular surgery during oral cancer resection (marginal mandibulectomy andor mandibulotomy) and 2 of 29 (6.9%) patients without mandibular surgery. The development of osteoradionecrosis was significantly associated with performing mandibular surgery (hazard ratio 4.64, 95% confidence interval 1.002, 21.5) and HIV infection (hazard ratio 8.53, 95% confidence interval 2.2, 33.3). In the subgroup analysis of mandibular surgery, the development of osteoradionecrosis significantly increased in patients undergoing mandibulotomy (hazard ratio 6.62, 95% confidence interval 1.3, 34.8) but not in patients undergoing marginal mandibulectomy (hazard ratio 3.56, 95% confidence interval 0.6, 22.0). The analysis also showed that concurrent chemoradiation, radiation doses ≥ 60 Gy, and smoking were potential risk factors for the development of osteoradionecrosis, but none of these factors were statistically significant. Conclusion Our findings suggest that mandibular surgery is a significant risk factor for the development of osteoradionecrosis in patients with oral cancer. Further studies including larger population sizes are required to verify these findings.

Herpes and Chest Pain Two Atypical Monkeypox Cases.

The 2022 Monkeypox Outbreak has spread globally in just a few months and has raised great concerns regarding disease recognition due to frequent atypical presentations and questions regarding the possibility of sexual transmission. In endemic countries and prior outbreaks, the clinical manifestations of monkeypox have been well documented, with cutaneous findings following a set, synchronous pattern of evolution. We present two cases of atypical monkeypox presentations in individuals living with HIV, both complicated by herpes simplex virus type 2 (HSV-2) coinfection and elevated troponins, and both demonstrating the ease with which monkeypox can be overlooked in the current outbreak.

Kaposi Sarcoma in an Immunocompetent Patient Treated With Paclitaxel.

Kaposi sarcoma (KS) is a rare multifocal tumor originating from the cells lining the blood vessels. It is characterized by vascular proliferation and is usually associated with immunosuppression due to multiple factors, including AIDS or organ transplantation. However, sporadic cases of KS have been reported in HIV-negative immunocompetent patients. Paclitaxel has shown efficacy and may be an alternative for the initial therapy of patients with KS. We report a case of KS in a 70-year-old Asian male who was HIV-negative, with no history of immunosuppression or homosexuality and a good response to treatment with Paclitaxel.

A Case of Left Ventricular Thrombus and Herpetic Esophagitis in an Immunocompetent Patient With COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with thrombosis, both venous and arterial, but the mechanism behind this coagulation is not fully understood. Several cases involving coronavirus disease 2019 (COVID-19)-positive patients with left ventricular thrombus (LVT), particularly in those with low ejection fraction, have been reported. This report describes a case of a 57-year-old male patient who presented to the hospital with altered mental status and a positive SARS-CoV-2 polymerase chain reaction (PCR) test. CT of the chest revealed the presence of an LVT, and transthoracic echocardiography showed a reduced ejection fraction and confirmed the presence of the thrombus. The patient also reported epigastric chest pain and several bloody bowel movements. A colonoscopy revealed internal hemorrhoids. An esophagogastroduodenoscopy revealed the presence of multiple esophageal ulcers, and biopsy results confirmed herpes simplex virus (HSV) infection. The patient had no history of organ or bone marrow transplant, long-term immunosuppressive therapy, or HIV infection. He was eventually discharged on apixaban for his LVT and acyclovir for his HSV esophagitis.

Shewanella algae, an Emerging Human Pathogen A Series of Four Cases From a Portuguese Hospital.

The prevalence of blood borne diseases in blood donors of Peshawar, Khyber Pakhtunkhwa, Pakistan.

The goal of the study was to investigate the burden of transfusion-transmitted infections (TTIs) hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), syphilis, and malarial parasite (MP) in ABO Blood Groups and Rh Type System among voluntarily blood donors in Khyber Pakhtunkhwa (KPK), Pakistan. It is a retrospective single center cross sectional study. This study was conducted from June 2020 to September 2021 (16 months) at the frontier foundation thalassemia center Peshawar KPK. Donors were physically healthy and fit for donation. Donors with physical disabilities andor having co-morbid conditions were excluded from the report. All the samples were screened for anti-HIV, anti-HCV, HBsAg, Syphilis, and Malarial Parasite via ELISA kit and Immune Chromatographic Technique (ICT), respectively. A total of 6311 blood donations were evaluated. The majority of the donations (92%) were from (VNRBD) voluntary non-remunerated blood donation, while only 8% came from replacement donors. Amongst 6311 blood donations, 1.50 % (n95) were infected at least with one pathogen, HBV positive cases were 0.855 % (n54), HCV positive cases were 0.316% (n20), syphilis positive were 0.30% (n19) and MP positive cases were only 0.031% (n2). HBV, HCV, syphilis and malaria infections rates were found to be low as compared to the previous data published, while no case was reported for HIV. The study also revealed the distribution pattern of the aforementioned pathogens in blood groups and the Rh type system of the reactive samples. The lower reported in our study indicates the awareness among the people of Peshawar about TTIs and their precautions. The prevalence rate that we are reporting is less than previously published articles in the same domain.

The Systems Analysis and Improvement Approach specifying core components of an implementation strategy to optimize care cascades in public health.

Healthcare systems in low-resource settings need simple, low-cost interventions to improve services and address gaps in care. Though routine data provide opportunities to guide these efforts, frontline providers are rarely engaged in analyzing them for facility-level decision making. The Systems Analysis and Improvement Approach (SAIA) is an evidence-based, multi-component implementation strategy that engages providers in use of facility-level data to promote systems-level thinking and quality improvement (QI) efforts within multi-step care cascades. SAIA was originally developed to address HIV care in resource-limited settings but has since been adapted to a variety of clinical care systems including cervical cancer screening, mental health treatment, and hypertension management, among others and across a variety of settings in sub-Saharan Africa and the USA. We aimed to extend the growing body of SAIA research by defining the core elements of SAIA using established specification approaches and thus improve reproducibility, guide future adaptations, and lay the groundwork to define its mechanisms of action. Specification of the SAIA strategy was undertaken over 12 months by an expert panel of SAIA-researchers, implementing agents and stakeholders using a three-round, modified nominal group technique approach to match core SAIA components to the Expert Recommendations for Implementing Change (ERIC) list of distinct implementation strategies. Core implementation strategies were then specified according to Proctors recommendations for specifying and reporting, followed by synthesis of data on related implementation outcomes linked to the SAIA strategy across projects. Based on this review and clarification of the operational definitions of the components of the SAIA, the four components of SAIA were mapped to 13 ERIC strategies. SAIA strategy meetings encompassed external facilitation, organization of provider implementation meetings, and provision of ongoing consultation. Cascade analysis mapped to three ERIC strategies facilitating relay of clinical data to providers, use of audit and feedback of routine data with healthcare teams, and modeling and simulation of change. Process mapping matched to local needs assessment, local consensus discussions and assessment of readiness and identification of barriers and facilitators. Finally, continuous quality improvement encompassed tailoring strategies, developing a formal implementation blueprint, cyclical tests of change, and purposefully re-examining the implementation process. Specifying the components of SAIA provides improved conceptual clarity to enhance reproducibility for other researchers and practitioners interested in applying the SAIA across novel settings.

Predictors of the observed high prevalence of loss to follow-up in ART-experienced adult PLHIV a retrospective longitudinal cohort study in the Tanga Region, Tanzania.

Antiretroviral therapy (ART) programs have expanded rapidly, and they are now accessible free of charge, yet loss to follow-up, LTFU is still a national public health issue. LTFU may result in treatment failure, hospitalization, increased risk of opportunistic infections and drug-resistant strains, and shortening the quality of life. This study described the rates and predictors of LTFU among adults living with human immunodeficiency virus (PLHIV) on ART in the Tanga region, Tanzania. A retrospective longitudinal cohort study was conducted between October 2018 and December 2020 in Tangas care and treatment health services facilities. The participants were HIV adult PLHIV aged 15 years and above on ART and attended the clinic at least once after ART initiation. LTFU was defined as not taking ART refills for 3 months or beyond from the last attendance of a refill and not yet classified as dead or transferred out. Cox proportional hazard regression models were employed to identify risk factors for LTFU. P values were two-sided, and we considered a p < 0.05 statistically significant. 57,173 adult PLHIV were on ART of them, 15,111 (26.43%) were LTFU, of whom 10,394 (68.78%) were females, and 4717 (31.22%) were males. Factors independently associated with LTFU involved age between 15 and 19 years (HR 1.85, 95% CI 1.66-2.07), male sex (HR 2.00 95% CI 1.51-2.62), divorce (HR 1.35, 95% CI 1.24-1.48), second-line drug type (HR 1.13, 95% CI 1.09-1.18), poor drug adherence (HR 1.50, 95% CI 1.23-1.75), unsuppressed viral load (HR 2.15, 95% CI 2.02-2.29), not on DTG-related drug (HR 7.51, 95% CI 5.88-10.79), advanced HIV disease WHO stage III and IV (HR 2.51, 95% CI 2.32-2.72). In contrast to cohabiting, ART duration < 1 year, and being pregnant showed a reduced likelihood of LTFU. A high prevalence of LTFU was observed in this study. Young age, not using DTG-based regimen, WHO clinical stage IV, poor drug adherence, male sex, unsuppressed viral load, divorcee, and second-line regime were independently associated with LTFU. To reduce LTFU, evidence-based interventions targeting the identified risk factors should be employed.

Finding influential subjects in a network using a causal framework.

Researchers across a wide array of disciplines are interested in finding the most influential subjects in a network. In a network setting, intervention effects and health outcomes can spill over from one node to another through network ties, and influential subjects are expected to have a greater impact than others. For this reason, network research in public health has attempted to maximize health and behavioral changes by intervening on a subset of influential subjects. Although influence is often defined only implicitly in most of the literature, the operative notion of influence is inherently causal in many cases influential subjects are those we should intervene on to achieve the greatest overall effect across the entire network. In this work, we define a causal notion of influence using potential outcomes. We review existing influence measures, such as node centrality, that largely rely on the particular features of the network structure andor on certain diffusion models that predict the pattern of information or diseases spreads through network ties. We provide simulation studies to demonstrate when popular centrality measures can agree with our causal measure of influence. As an illustrative example, we apply several popular centrality measures to the HIV risk network in the Transmission Reduction Intervention Project and demonstrate the assumptions under which each centrality can represent the causal influence of each participant in the study. This article is protected by copyright. All rights reserved.

The gut microbiome and early-life growth in a population with high prevalence of stunting.

Stunting affects one-in-five children globally and is associated with greater infectious morbidity, mortality and neurodevelopmental deficits. Recent evidence suggests that the early-life gut microbiome affects child growth through immune, metabolic and endocrine pathways. Using whole metagenomic sequencing, we map the assembly of the gut microbiome in 335 children from rural Zimbabwe from 1-18 months of age who were enrolled in the Sanitation, Hygiene, Infant Nutrition Efficacy Trial (SHINE NCT01824940), a randomized trial of improved water, sanitation and hygiene (WASH) and infant and young child feeding (IYCF). Here, we show that the early-life gut microbiome undergoes programmed assembly that is unresponsive to the randomized interventions intended to improve linear growth. However, maternal HIV infection is associated with over-diversification and over-maturity of the early-life gut microbiome in their uninfected children, in addition to reduced abundance of Bifidobacterium species. Using machine learning models (XGBoost), we show that taxonomic microbiome features are poorly predictive of child growth, however functional metagenomic features, particularly B-vitamin and nucleotide biosynthesis pathways, moderately predict both attained linear and ponderal growth and growth velocity. New approaches targeting the gut microbiome in early childhood may complement efforts to combat child undernutrition.

Environmentally benign synthesis of unsymmetrical ureas and their evaluation as potential HIV-1 protease inhibitors via a computational approach.

The present work reports the cost-effective, high yielding and environmentally acceptable preparation of unsymmetrical ureas from thiocarbamate salts using sodium percarbonate as an oxidant. Efficacy of the unsymmetrical ureas as potential human immune deficiency virus (HIV-1) protease inhibitors has been evaluated via in silico approach. The results revealed interactions of the urea compounds at the active site of the enzyme with favorable binding affinities causing possible mutations hindering the functioning of the enzyme. Further computational assessment of IC50 using known references satisfactorily authenticated the inhibitory action of the selected compounds against HIV-1 protease. Added to the easy synthesis of the ureas following an environmentally benign protocol, this work may be a valuable addition to the ongoing search for drugs with better efficacy profiles and reduced toxicity against HIV.

Effectiveness of Behavioural Economics Informed Interventions for the Prevention, Screening, and Antiretroviral Treatment of HIV Infection A Systematic Review of Randomized Controlled Trials.

Failure to meet international targets set for the human immunodeficiency virus HIV pandemic suggests that more effective public health strategies are needed. New strategies informed by behavioural economics are now increasingly being tested, with promising results. However, the evidence base is diverse and challenging for policymakers to interpret. This paper aims to synthesise existing evidence by reporting results from a systematic review of behavioural economics-based interventions for addressing HIV prevention, testing and treatment. The reported study was a systematic review of randomized controlled trials. The search was conducted in four electronic medical literature databases, six trial registries, four grey literature sources and was not restricted to any country or region. Bias was assessed using criteria outlined in the Cochrane Handbook for Systematic Reviews quality of evidence was assessed using GRADE methodology. Fifteen full text articles were included in the final analysis. The synthesis of these studies revealed that strategies involving opt-out defaults, active-choice defaults, and lottery incentives can potentially increase uptake of HIV testing. Lottery incentives also showed signs of effectiveness in improving HIV prevention, ART adherence and initiation. Despite the promising findings, the overall evidence was judged to be of moderate to very low quality. Behavioural economics-based interventions are promising behavioural change strategies, although more well-designed studies are needed to strengthen the evidence base.

Impact of Community Support Workers in Rural Ethiopia on Emotional and Psychosocial Health of Persons Living with HIV Results of a Three-Year Randomized Community Trial.

People living with HIV face multiple psychosocial challenges. In a large, predominantly rural Ethiopian region, 1799 HIV patients new to care were enrolled from 32 sites in a cluster randomized trial using trained community support workers with HIV to provide individual health education, counseling and social support. Participants received annual surveys through 36 months using items drawn from the Centre for Epidemiologic Studies Depression Scale-10, Medical Outcome Study Social Support Survey, and HIVAIDS Stigma Instrument-PLWA. At 12 months (using linear mixed effects regression models controlling for enrollment site clustering), intervention participants had greater emotionalinformational and tangible assistance social support scores, and lower scores assessing depression symptoms and negative self-perception due to HIV status. A significant treatment effect at 36 months was also seen on scores assessing emotionalinformational social support, depression symptoms, and internalized stigma. An intervention using peer community support workers with HIV to provide individualized informational and psychological support had a positive impact on the emotional health of people living with HIV who were new to care.(ClinicalTrials.gov protocol ID 1410S54203, May 19, 2015).

Effect of double-dose levonorgestrel subdermal implant in women taking efavirenz-based antiretroviral therapy The DoubLNG pharmacokinetic study.

We evaluated the pharmacokinetics of double-dose levonorgestrel implants to overcome the drug-drug interaction with efavirenz-based antiretroviral therapy (ART). We conducted a non-randomized, open-label, parallel-group, longitudinal pharmacokinetic study among Ugandan women ages 18 to 45 years. Participants with HIV on ART containing efavirenz 600mg received 300mg LNG implants (Jadelle®, Bayer, New Zealand) 300LNGART group. We compared our outcomes with women without HIV using standard dose, 150mg LNG implants 150LNG group. The implant was placed on day 0 in both groups, and we quantified plasma LNG concentrations over 48 weeks post-implant insertion. LNG pharmacokinetic parameters were estimated using noncompartmental techniques. Our primary outcome was the geometric mean ratio (GMR) with 90% confidence intervals (CI) of LNG area under the concentration-time curve over 24 weeks (AUC We enrolled 27 women in the 300LNGART group 34 (28.0-40.5) years and 61.0 (49.8-66.0) kg and 19 women in the 150LNG group 33 (30.0-34.5) years and 64.9 (59.0-74.5) kg. LNG AUC Double-dose LNG implant did not completely overcome the drug-drug interaction with efavirenz. In women using antiretroviral therapy (ART) containing efavirenz, placing two implant systems (300mg) did not normalize LNG pharmacokinetics compared with the standard-dose implant (150mg), and some women had evidence of ovulatory activity. Alternative ART without drug-drug interactions, such as dolutegravir, are recommended with contraceptive implants.

Weight change following switch to dolutegravir for HIV treatment in rural Kenya during country roll-out.

Switch to dolutegravir (DTG) in treatment-experienced people living with HIV (PLH) is associated with excess weight gain in some settings data are limited from rural low-income settings with low obesity prevalence. In rural Kenya, we conducted a retrospective cohort study at eight HIV clinics and a single-site prospective cohort study including adults switching to DTG during countrywide transition to DTGtenofovir DF(TDF)emtricitabine as first-line HIV treatment. In the retrospective analysis, we used pre-switch data to model post-switch weight trajectory had each participant not switched to DTG and contrasted observed vs. predicted post-switch weight. In the prospective analysis, we measured weight post-DTG switch and evaluated predictors of 6-month weight change. Our retrospective cohort included 4,445 PLH who switched to DTG between 2018-2020. Mean 12-month weight change was 0.6kg pre-switch and 0.8kg post-switch. Among those on TDF throughout (n3,374 83% on efavirenz pre-switch), 12-month post-switch weight was 0.7kg more than predicted for women (95%CI 0.4, 1.0) and similar among men (0.04kg 95%CI -0.3, 0.4). In our prospective cohort (n135, 100% female), mean 6-month weight change was 0.4kg (IQR -1.1, 2.0). Predicted gain varied by baseline food insecurity 1.1kg (95%CI 0.34, 1.87) among food-secure, -0.09kg (95%CI -0.71, 0.54) among moderate-insecure, and 0.27kg (95%CI -0.82, 1.36) among severe-insecurity. In contrast to some reports of large weight gain following switch to DTG, we observed small weight increases in women and no weight change in men following DTG switch when on TDF throughout. Weight gain may be attenuated by food insecurity, though was modest even among food-secure.

Recent advances on dual inhibitors targeting HIV reverse transcriptase associated polymerase and ribonuclease H.

Reverse transcriptase (RT) plays an indispensable role in the replication of human immunodeficiency virus (HIV) through its associated polymerase and ribonuclease H (RNase H) activities during the viral RNA genome transformation into proviral DNA. Due to the fact that HIV is a highly mutagenic virus and easily resistant to single-target RT inhibitors, dual inhibitors targeting HIV RT associated polymerase and RNase H have been developed. These dual inhibitors have the advantages of increasing efficacy, reducing drug resistance, drug-drug interactions, and cytotoxicity, as well as improving patient compliance. In this review, we summarize recent advances in polymeraseRNase H dual inhibitors focusing on drug design strategies, and structure-activity relationships and share new insights into developing anti-HIV drugs.

Prevalencia de glucosa alterada en ayuno y dislipidemia entre pacientes mexicanos con VIH naïve a tratamiento antirretroviral.

Metabolic complications have become more relevant in the care of patients with HIV. However, little is known about the incidence and risk factors for these disorders among HIV-infected antiretroviral treatment naïve (ARTn) patients. To recognize the prevalence of Impaired Fasting Glucose (IFG) and dyslipidemia among HIV-infected ARTn Mexican individuals and identify associated risk factors. A retrospective study was conducted in HIV-1-infected ART-N patients, referred for attention to a general hospital in Mexico City, between 2009 and 2019. We collected information for anthropometric, clinical, biochemical and HIV status variables. We included 221 patients, 97% were males, mean age 30 years (interquartile range IQR 25-38) median CD4 count was 250 cellsmm IFG and dyslipidemia are highly prevalent among HIV-infected ART-naïve Mexican patients, therefore, screening for glucose and lipids abnormalities always should be considered among ARTn patients. Las alteraciones metabólicas se han vuelto más relevantes en el cuidado de los pacientes con infección por el virus de la inmunodeficiencia humana (VIH). Existe poca información sobre estas alteraciones en pacientes naïve a tratamiento antirretroviral (nTAR). Identificar la prevalencia de glucosa alterada en ayuno y dislipidemia entre individuos mexicanos con VIH nTAR e identificar los factores asociados. Estudio retrospectivo en pacientes con VIH nTAR valorados en un hospital general de la Ciudad de México de 2009 a 2019. Se recabaron datos antropométricos, clínicos, bioquímicos y relacionados con el estado del VIH. Se incluyeron 221 pacientes, el 97% hombres, con mediana de edad 30 años (rango intercuartil RIC 25-38), cuenta de linfocitos CD4 250 célulasmm Las alteraciones en el metabolismo de los lípidos y de la glucosa son frecuentes entre individuos mexicanos con VIH nTAR por lo tanto, es importante una adecuada evaluación antes de iniciar el tratamiento.

Rare Co-Infection of the Lungs with EBV and Pneumocystis Carinii in a Patient with Kidney Cancer a Case Report.

Epstein-Barr virus (EBV) is the primary agent of infectious mononucleosis, lymphoma, and naso-pharyngeal carcinoma, but rarely involves the lungs. Pneumocystis carinii is commonly found in patients with HIV infection and is not pathogenic when the host is healthy, but opportunistic infections can occur when the body is immunocompromised, causing pneumocystis pneumonia (PCP). It is rare for both diseases to occur in the lungs of the same patient. Next-generation sequencing (NGS), laboratory examination, chest CT scan, electronic bronchoscopy, and pathogenetic examination were used in this study. Laboratory tests showed (1-3)-β-D-glucan of 889.47 pgmL, negative human immunodeficiency virus (HIV) antibody, and negative Aspergillus immunological test. Chest CT showed multiple high-density shadows in both lungs, and EBV infection combined with Pneumocystis carinii pneumonia was confirmed by bronchoscopic biopsy and NGS examination. Elevated serum (1-3)-β-D-glucan is not a specific index for infectious diseases. Bronchoscopy and the NGS has high specificity in pathogen detection of infectious diseases.

The Prevalence of Transfusion-Transmitted Infection Markers among Blood Donors at Saudi Hospital, Makkah.

Testing of blood donors for markers of transfusion-transmitted infections (TTIs) such as HBV, HCV, HIV, HTLV, syphilis, and malaria is mandatory in Saudi Arabia. This study determined the prevalence of all tested TTIs among blood donors in the western region of Saudi Arabia. This retrospective study included 5,473 blood donors who attended the blood donation center at the Security Force Hospital (SFH) located in the western region of Saudi Arabia from January 1, 2015 to December 31, 2018. The prevalence of TTIs was determined and classified as per year, gender, age, type of donors (first-time vs. returned donors), category of donation (replacement vs. volunteer), and blood group. All donors (100%) were screened for TTIs by serological assays and nucleic acid tests (NATs). Reactive samples to serological assays were as follow 57 (1.07%) HBsAg, 292 (5.34%) HBsAb, 388 (7.1%) HBcAbs, 13 (0.24%) HCV, 5 (0.09%) HIV, 8 (0.15%) HTLV-I and -II, 21 (0.83%) syphilis, and 0 (0%) malaria. The NAT results for HBV, HCV, and HIV revealed 50 (0.91%), 1 (0.0002%), and 3 (0.05%) reactive samples, respectively. Reactive donations to screening serology tests of syphilis and HTLV-I-II were neither confirmed nor declined by their corresponding confirmatory assays. Most reactive samples to TTI tests were associated with male gender, first-time donor, replacement donation, and O blood group. This study highlights the strong adherence to TTI testing policy and low prevalence of TTI markers among blood donors in the western region of Saudi Arabia.

Pyranonaphthoquinones and Naphthoquinones from the Stem Bark of

Seven previously undescribed compounds, including five pyranonaphthoquinones (ventilanones L-P) and two naphthoquinones (ventilanones Q and R), along with 15 known compounds were isolated from the stem bark of

Understanding the Risk of Drug Interactions Between Ritonavir-Containing COVID-19 Therapies and Small-Molecule Kinase Inhibitors in Patients With Cancer.

The introduction of COVID-19 therapies containing ritonavir has markedly expanded the scope of use for this medicine. As a strong cytochrome P450 3A4 inhibitor, the use of ritonavir is associated with a high drug interaction risk. There are currently no data to inform clinician regarding the likely magnitude and duration of interaction between ritonavir-containing COVID-19 therapies and small-molecule kinase inhibitors (KIs) in patients with cancer. Physiologically based pharmacokinetic modeling was used to conduct virtual clinical trials with a parallel group study design in the presence and absence of ritonavir (100 mg twice daily for 5 days). The magnitude and time course of changes in KI exposure when coadministered with ritonavir was evaluated as the primary outcome. Dosing of ritonavir resulted in a > 2-fold increase in steady-state area under the plasma concentration-time curve and maximal concentration for six of the 10 KIs. When the KI was coadministered with ritonavir, dose reductions to between 10% and 75% of the original dose were required to achieve an area under the plasma concentration-time curve within 1.25-fold of the value in the absence of ritonavir. To our knowledge, this study provides the first data to assist clinicians understanding of the drug interaction risk associated with administering ritonavir-containing COVID-19 therapies to patients with cancer who are currently being treated with KIs. These data may support clinicians to make more informed dosing decisions for patients with cancer undergoing treatment with KIs who require treatment with ritonavir-containing COVID-19 antiviral therapies.

Tilting the Scale Current Provider Perspectives and Practices on Breastfeeding with HIV in the United States.

The risk of vertical transmission from breastfeeding with HIV (BFHIV) has been found to be very low in optimal scenarios with sustained maternal viral suppression during pregnancy and postpartum. Medical providers must account for the risk of this serious adverse event alongside parental autonomy, breastfeeding benefits, and patient values. To assess provider practices, comfort, and challenges with BFHIV, an online mixed-method survey was sent to breastfeeding and HIV provider listservs from June to July 2021. The target population was US medical professionals from diverse practice settings with experience in clinical issues associated with BFHIV, including physicians, advanced practice providers, nurses, and lactation consultants. Data analysis utilized nonparametric hypothesis testing, ordinal regression, and reflexive thematic analysis. Most providers reported counseling pregnant people with HIV on infant feeding choices, but fewer specifically endorsed counseling about breastfeeding. Of 84 unique institutions identified by 100 included respondents, 10% had an institutional protocol supporting BFHIV. Institutional protocols were associated with higher degrees of provider comfort with BFHIV in optimal scenario clinical vignettes. Providers perceived that White patients faced fewer BFHIV barriers than patients with other racial identities. Discomfort balancing the goals to protect infants from infection risk and support the parents role in infant feeding decisions was a key theme in free text responses this manifested in a spectrum of management styles ranging from patients informed choice to paternalism. This study highlights the tension providers navigate regarding BFHIV discussions, calling for patient care guidelines and protocols grounded in risk reduction and respect of patient autonomy.

Performances of Dried Blood Spots and Point-of-Care Devices to Identify Virological Failure in HIV-Infected Patients A Systematic Review and Meta-Analysis.

To broaden access to HIV viral load monitoring (VLM), the use of blood samples from dried blood spots (DBS) or point-of-care (POC) devices, could be of great help in settings where plasma is not easily accessible. The variety of assays available makes the choice complex. This systematic review and meta-analysis aims to estimate the sensitivity and specificity of DBS and POC devices to identify patients in virological failure using World Health Organization (WHO) recommendations (viral load ≥1000 copiesmL), compared with plasma, for the assays currently available. Four databases were searched for articles, and two reviewers independently identified articles reporting sensitivity and specificity of DBS andor POC to identify patients in virological failure. We excluded articles that used other thresholds as well as articles with a total number of participants below 50 to avoid reporting bias. Heterogeneity and factors associated with assays performances were assessed by

Knowledge, beliefs and practices towards HIVAIDS among adolescents in India A scoping review protocol.

Acquired Immune Deficiency Syndrome (AIDS) is a major health concern among Indian adolescents (10-19 years). Indian adolescents lack adequate knowledge about HIVAIDS and adopt wrong practices. The present scoping review aims to understand the status of knowledge, beliefs and practices among Indian adolescents about HIV or HIVAIDS. The present study will also focus on their understanding and the source of knowledge and awareness regarding HIVAIDS. The recommendations of Arksey and OMalley in 2005, Levac et al. in 2010 and The Joanna Briggs Institute Reviewers manual in 2015 to conduct a systematic scoping review will be employed. The review questions, eligibility criteria and search strategy for this study will be ensured by the Population, Concept and Context (PCC) strategy. The Preferred Reporting Items for Systemic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) will be used for reporting of this scoping review. The methodological quality of all the relevant studies will be assessed by the Mixed Methods Appraisal Tool (MMAT), Version- 2018. Literature search will be carried out by using electronic databases such as PubMed, APA PsycInfo, EMBASE, and Google Scholar. Cross-references will be used to extract additional studies. As the planned study is based on secondary data and doesnt involve human and animal subjects, there is no requirement for formal ethical approval. The planned scoping review is the first of such study on the topic of HIVAIDS among adolescent population in India as per the electronically available literature.There will be quality assessment of all the included studies.A thorough search strategy will be conducted as per the recommendations of the experts in scoping review search.On limitation side, the planned study will only utilize electronically available resourcesevidences that are written in English language.The planned evidence based study will be of much help for the healthcare professionals and policy makers.

Pregnant women and male partner perspectives of secondary distribution of HIV self-testing kits in Uganda A qualitative study.

HIV self-testing (HIVST) is a promising strategy to increase awareness of HIV status among sub-Saharan African (SSA) men. Understanding user perspectives on HIVST secondary distribution from pregnant women attending antenatal care (ANC) to their male partners is crucial to optimizing delivery strategies. We sampled pregnant women attending ANC without their partners and purposively oversampled pregnant women living with HIV (PWHIV) to understand their unique views. We recruited male partners after obtaining contact information from women. We conducted 14 focus group discussions and 10 in-depth interviews with men and pregnant women. We assessed acceptability of HIVST secondary distribution, barriers, facilitators, and interventions to increase HIVST uptake. Participants felt that HIVST secondary distribution was acceptable, particularly for women in stable relationships. However, many expressed concerns about accusations of mistrust, relationship dissolution, fear of discovering serodifference, and lack of counseling associated with HIVST. PWHIV reported hesitation about secondary distribution, citing fears of unintended HIV status disclosure and abandonment resulting in financial hardship for themselves and their infant. Some participants preferred that providers contact men directly to offer HIVST kits instead of distribution via women. Participants reported that community sensitization, availability of phone-based counseling, male clinic staff, extended clinic hours, and financial incentives could increase mens HIVST use and linkage to care. Participants expressed high interest in using HIVST, but secondary distribution was not universally preferred. We identified potential strategies to increase HIVST acceptability, particularly among PWHIV and those in unstable partnerships which can inform strategies to optimize HIVST distribution.

Clinic-based SAMBA-II vs centralized laboratory viral load assays among HIV-1 infected children, adolescents and young adults in rural Zimbabwe A randomized controlled trial.

In Zimbabwe, children, adolescents and young adults living with HIV (CALWH) who are on public health antiretroviral therapy (ART) have inadequate viral load (VL) suppression. We assessed whether a clinic-based VL monitoring could decrease 12-month virologic failure rates among these CALWH. The study was registered on ClinicalTrials.gov NCT03986099. CALWH in care at Chidamoyo Christian Hospital (CCH) and 8 rural outreach sites (ROS) on long-term community-based ART were randomized (11) to 6 monthly VL monitoring by COBAS®Ampliprep®Taqman48® HIV-1 at the provincial referral laboratory (PRL) as per standard of care (SOC) or by the clinic-based SAMBA II assay, Diagnostics for the Real World, at CCH. VL suppression, turn-around-time (TAT) for VL results, drug switching and drug resistance in second-line failure were assessed at 12 months. Of 390 CALWH enrolled 347 (89%) completed 12 months follow-up. Median (IQR) age and ART duration were 14.1 (9.7-18.2) and 6.4 (3.7-7.9) years, respectively. Over half (57%) of the participants were female. At enrolment, 78 (20%) had VL ≥1,000 copiesml and VL suppression of 80% was unchanged after 12 months, with no significant difference between the SOC (81%) and the clinic-based (80%) arms (p 0.528). Median (IQR) months to confirmatory VL result at CCH vs PRL was 4.0 (2.1-4.4) vs 4.5 (3.5-6.3) respectively p 0.027 at 12 months. Drug switching was documented among 26347 (7%) participants with no difference between the median (IQR) time to switch in SOC vs clinic-based arms (5.1 (3.9-10.0) months vs 4.4 (2.5-8.4) respectively p 0.569). Out of 24 confirmed second-line failures, only 419 (21%) had protease inhibitor resistance. In rural Zimbabwe, the clinic-based SAMBA II assay was able to provide confirmatory VL results faster than the SOC VL assay at the PRL. However, this rapid TAT did not allow for a more efficient drug switch among these CALWH.

Modelling the transmission dynamics and optimal control strategies for HIV infection in China.

In order to end the AIDS epidemic by 2030 that was put forward by the Joint United Nations Programme on HIVAIDS in 2014, China needs to take more effective measures to achieve the three 90% goals (90-90-90). We establish a compartmental model to study the dynamics of HIV transmission with control strategies. The analytical results show the existence and stability of the disease-free equilibrium and endemic equilibrium. An optimal control model is constructed to evaluate the impacts of control measures. The simulation results show that the optimal control strategy proposed in this work can eradicate AIDS by 2030. The cost-effectiveness analysis indicates that the cost of the control strategy that combines screening for latent individuals and enhancing education for unaware infected individuals is the lowest. Our findings can provide guidance for public health authorities on effective mitigation strategies to achieve the goals proposed by the United Nations Program on HIVAIDS.

Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults.

BACKGROUNDMosaic and consensus HIV-1 immunogens provide two distinct approaches to elicit greater breadth of coverage against globally circulating HIV-1 and have shown improved immunologic breadth in nonhuman primate models.METHODSThis double-blind randomized trial enrolled 105 healthy HIV-uninfected adults who received 3 doses of either a trivalent global mosaic, a group M consensus (CON-S), or a natural clade B (Nat-B) gp160 env DNA vaccine followed by 2 doses of a heterologous modified vaccinia Ankara-vectored HIV-1 vaccine or placebo. We performed prespecified blinded immunogenicity analyses at day 70 and day 238 after the first immunization. T cell responses to vaccine antigens and 5 heterologous Env variants were fully mapped.RESULTSEnv-specific CD4 T cell responses were induced in 71% of the mosaic vaccine recipients versus 48% of the CON-S recipients and 48% of the natural Env recipients. The mean number of T cell epitopes recognized was 2.5 (95% CI, 1.2-4.2) for mosaic recipients, 1.6 (95% CI, 0.82-2.6) for CON-S recipients, and 1.1 (95% CI, 0.62-1.71) for Nat-B recipients. Mean breadth was significantly greater in the mosaic group than in the Nat-B group using overall (P 0.014), prime-matched (P 0.002), heterologous (P 0.046), and boost-matched (P 0.009) measures. Overall T cell breadth was largely due to Env-specific CD4 T cell responses.CONCLUSIONPriming with a mosaic antigen significantly increased the number of epitopes recognized by Env-specific T cells and enabled more, albeit still limited, cross-recognition of heterologous variants. Mosaic and consensus immunogens are promising approaches to address global diversity of HIV-1.TRIAL REGISTRATIONClinicalTrials.gov NCT02296541.FUNDINGUS NIH grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069412, UL1 RR025758, P30 AI064518, UM1 AI100645, and UM1 AI144371, and Bill Melinda Gates Foundation grant OPP52282.

A dynamical analysis and numerical simulation of COVID-19 and HIVAIDS co-infection with intervention strategies.

HIVAIDS-COVID-19 co-infection is a major public health concern especially in developing countries of the world. This paper presents HIVAIDS-COVID-19 co-infection to investigate the impact of interventions on its transmission using ordinary differential equation. In the analysis of the model, the solutions are shown to be non-negative and bounded, using next-generation matrix approach the basic reproduction numbers are computed, sufficient conditions for stabilities of equilibrium points are established. The sensitivity analysis showed that transmission rates are the most sensitive parameters that have direct impact on the basic reproduction numbers and protection and treatment rates are more sensitive and have indirect impact to the basic reproduction numbers. Numerical simulations shown that some parameter effects on the transmission of single infections as well as co-infection, and applying the protection rates and treatment rates have effective roles to minimize and also to eradicate the HIVAIDS-COVID-19 co-infection spreading in the community.

Leveraging mHealth and Patient Supporters for African Americans and Latinxs Engagement in HIV Care (LEAN) Protocol for a Randomized, Controlled, Effectiveness-Implementation Trial.

Despite substantial investments in ending the HIV epidemic, disparities in HIV care persist, and there is an urgent need to evaluate novel and scalable approaches to improving HIV care engagement and viral suppression in real-world settings. This paper aims to describe a study protocol for a pragmatic type II hybrid effectiveness-implementation randomized controlled trial comparing existing standard of care clinic HIV linkage, adherence, and retention (LAR) protocols to a mobile health (mHealth)-enhanced linkage, adherence, and retention (mLAR) intervention. The study will enroll 450 participants from clinics in Baltimore City. Eligibility criteria include being ≥18 years of age, having a new HIV diagnosis or being HIV-positive and out of care, or being HIV-positive and deemed by clinic staff as someone who could benefit from linkage and retention services. Participants randomized to the intervention receive mHealth-supported patient navigation for 12 months. Participants in the control group receive the referring clinics standard of care patient support. The primary outcome is HIV virologic suppression at 12 months. A subset of participants will be interviewed at 12 months to learn about their HIV care experiences and, for those in the intervention arm, their experiences with the mLAR intervention. This protocol was developed in collaboration with the Baltimore City Health Department (BCHD) and the Maryland Department of Health (MDH) and with input from a community advisory board. Enrollment began on February 25, 2020. As of August 11, 2022, 411 of the 450 target participants had been enrolled. Pragmatic implementation science trials designed with input from key stakeholders, including health departments and community members, can help evaluate the evidence for mHealth interventions to reduce HIV health disparities. ClinicalTrials.gov NCT03934437 httpsclinicaltrials.govct2showNCT03934437. DERR1-10.219642691.

Additive cortical gray matter deficits in people living with HIV who use cocaine.

Cocaine use, which is disproportionately common in people living with HIV (PWH), is known to have neurotoxic effects that may exacerbate HIV neuropathogenesis. While both cocaine use and HIV disease are independently associated with deficits in gray matter (GM) volume, the additive effect of cocaine use to HIV disease on GM volume has not been explored. Here, we investigated subcortical and cortical brain volume differences between four groups of individuals with and without HIV disease andor cocaine use. Participants also completed a comprehensive neuropsychological testing battery, and HIV disease characteristics were recorded. Within subcortical regions, cocaine use was independently associated with higher volume in the dorsal striatum and pallidum, while HIV disease was associated with lower volume in the nucleus accumbens and thalamus. For cortical regions, there was an additive effect of cocaine use on HIV disease in parietal and occipital lobe volume with PWH who used cocaine displaying the lowest GM volume. Within regions that differed between groups, higher neurocognitive function was positively associated with thalamic, nucleus accumbens, dorsal striatum, and occipital lobe volume. For regions that showed a significant main effect of HIV disease, lower nadir CD4 T cell count was associated with lower nucleus accumbens and occipital lobe volume. Lower current CD4 T cell count was associated with lower occipital lobe volume. These results suggest that PWH who use cocaine are at greater risk for cortical atrophy than cocaine use or HIV disease alone.

Variations in Pre-exposure Prophylaxis (PrEP) Awareness and Healthcare Provider Interactions in a Nationally Representative Sample of American Men Aged 15-49 Years A Cross-Sectional Study.

Awareness of and discussions with a healthcare provider (HCP) around pre-exposure prophylaxis (PrEP), an effective HIV prevention method, are associated with PrEP uptake, yet few studies utilize representative samples or report on these outcomes using distinct behavioral risk subgroups. This cross-sectional study utilized responses given by men on the 2017-2019 National Survey of Family Growth, a nationally representative survey of Americans aged 15-49 years. Multiple logistic regression models were used to determine how respondents sociodemographic characteristics and HIV risk behaviors were related to PrEP awareness and HCP discussions. PrEP awareness was low (29.40%) as was the proportion who reported ever discussing PrEP with an HCP (4.48%). Odds of being PrEP aware and discussing PrEP with an HCP varied significantly within sexual behavior subgroups based on sociodemographic and behavioral characteristics highlighting the differential risks within distinct behavioral subgroupings of men. Sexual behavior subgroupings should be considered when promoting PrEP awareness and discussions as HIV risk behaviors vary considerably and sexual identity alone may not sufficiently capture ones HIV risk.

Verbal Memory Performance and Depressive Symptoms in Persons with Treated HIV.

The link between memory and comorbid depression in persons with HIV (PWH) is unclear based on evidence from published cohorts. We compared verbal memory in the HVLT-R in a well-characterized HIV cohort (n 354) with (n 102) or without (n 252) comorbid depressive symptoms, and examined memory correlates in both scenarios. Memory fell within unimpaired ranges, but was lower in depressed than non-depressed PWH. Memory was related to quality of life, sociodemographic, and mental health factors, but not to assessed HIV-related or antiretroviral factors. However, longitudinally (n 52) memory declined with presence and severity of depressive symptoms. In this treated cohort, verbal memory was unrelated to HIV-related variables but to quality of life and depressive symptoms. Greater performance decline over time also related to acute or ongoing depressive symptoms. These findings highlight the importance of addressing comorbid depressive symptoms to improve quality of life in persons with treated HIV.

Barriers to Condom Negotiation and Use Among Female Sex Workers in the United States and United States-Mexico Border Cities A Systematic Review.

Despite the effectiveness of male condoms, many Female Sex Workers (FSWs) report using condoms infrequently with multiple clients during sexual activity. As such, inconsistent condom use by FSWs is a public health concern as it can increase STI and HIV transmission. This systematic review synthesized extant evidence regarding barriers to condom use experienced by FSWs in the U.S and U.S. - Mexico border towns. The search was conducted through PubMed, CINAL, Cochrane, Medline, and PsychInfo. Studies were included if they were conducted in the U.S. or U.S. - Mexico borders, their target population was FSWs, they examined condom use barriers experienced by FSWs, and they were published in English between 2011 and February 2021. Condom use barriers among FSWs were reported in all the articles including alcohol consumption and drug use before sex, venue stability, socio-economic status vulnerability, violence and gendered power dynamics, trust of regular clients, and age. The review findings indicate the need to develop interventions promoting condom use for both FSWs and their clients, as well as alternative interventions for HIV prevention such as pre-exposure prophylaxis (PrEP).

Does the Association Between Stimulant use and High Risk Sexual Behavior Vary by Injection Drug Use, Sexual Minority Status, or HIV Infection Status A Meta-analysis.

There is strong evidence linking stimulant use, namely methamphetamine use, to sexual risk behavior among sexual minority men (SMM) we do not, however, have a good understanding of this relationship among other at-risk populations. In this study, we systematically reviewed associations between stimulant use (i.e., methamphetamine, crack cocaine, cocaine) and sexual risk behaviors among populations facing elevated risk of HIV transmission and acquisition (i.e., SMM, people who inject drugs (PWID), and people living with HIVAIDS (PLWH)). Random-effects meta-analyses and sensitivity analyses that included crude and adjusted estimates separately were conducted to evaluate the impact of potential confounding variables. The results showed strong relationships between stimulant use and condomless sex, transactional sex, and multiple sexual partners. Results were broadly consistent when analyses were stratified by type of stimulant (methamphetamine, crack cocaine, and other stimulants) and risk group. Sensitivity analyses with confounding variables did not greatly impact results. The results indicate that stimulant use is associated with numerous sexual risk behaviors regardless of risk group, suggesting prevention efforts focused on reducing methamphetamine-related HIV risk should target a range of at-risk populations.

Phospholipase B Is Critical for Cryptococcus neoformans Survival in the Central Nervous System.

Cryptococcus neoformans (

Monkeypox awareness and low vaccination hesitancy among men who have sex with men in China.

Men who have sex with men (MSM) have been recommended for targeted monkeypox vaccination. We aimed to investigate monkeypox awareness and explore the correlates of monkeypox vaccination hesitancy among MSM in China. We conducted a cross-sectional survey from August 10 to September 9, 2022. Awareness related to monkeypox and attitude towards monkeypox vaccination among MSM aged ≥18 years were collected. Multivariable logistic regression was applied to evaluate correlates of vaccination hesitancy. Discrepancy in awareness between subgroups regarding HIV status was assessed. A total of 1090 MSM were included (age median 30 years, IQR, 25-35 HIV-infected 53.12%). Only 13.85% respondents expressed high monkeypox vaccination hesitancy. Hesitancy was associated with no fixed income (aOR, 2.46, 95% CI, 1.48-4.11), infrequent information following (sometimes, 3.01, 1.55-5.83 seldom or never, 5.66, 2.58-12.45), and lack of worries about monkeypox endemic (1.78, 1.11-2.87). Participants who believed that HIV-infected cases accounted for a smaller proportion (1.62, 1.01-2.60), disagreed that monkeypox virus could be detected in semen (2.21, 1.26-3.88), and considered either replication-competent (1.84, 1.14-2.96) or replication-deficient (4.80, 2.26-10.21) monkeypox vaccine unsuitable for HIV-infected people were generally more hesitant. Compared with HIV-uninfected MSM, HIV-infected MSM supported more for vaccination promotion. MSM in China had low hesitancy towards monkeypox vaccination. Safety and affordability of vaccine, and availability of information were essential aspects to reduce hesitancy. Education on vaccination benefits should be encouraged to promote future vaccination plans. This article is protected by copyright. All rights reserved.

Delirium among people aging with and without HIV Role of alcohol and Neurocognitively active medications.

People aging with and without HIV (PWH and PWoH) want to avoid neurocognitive dysfunction, especially delirium. Continued use of alcohol in conjunction with neurocognitively active medications (NCAMs) may be a largely underappreciated cause, especially for PWH who experience polypharmacy a decade earlier than PWoH. We compare absolute and relative risk of delirium among PWH and PWoH by age, level of alcohol use, and exposure to NCAMs. Using the VACS cohort, we compare absolute and relative risk of inpatient delirium among PWH and PWoH by age, level of alcohol use, and exposure to NCAMs between 2007 and 2019. We matched each case based on age, raceethnicity, sex, HIV, baseline year, and observation time with up to 5 controls. The casecontrol date was defined as date of admission for cases and the date corresponding to the same length of time on study for controls. Level of alcohol use was defined using Alcohol Use Disorder Identification Test-Consumption (AUDIT-C). Medication exposure was measured from 45 to 3 days prior to index date medications were classified as anticholinergic NCAM, non-anticholinergic NCAM, or non NCAM and counts generated. We used logistic regression to determine odds ratios (ORs) for delirium associated with medication counts stratified by HIV status and adjusted for demographics, severity of illness, and related diagnoses. PWH experienced a higher incidence of delirium (5.6, 95% CI 5.3-5.91000 PY) than PWoH (5.0, 95% CI 4.8-5.11000 PY). In multivariable analysis, anticholinergic and non-anticholinergic NCAM counts and level of alcohol use demonstrated strong independent dose-response associations with delirium. Decreasing alcohol use and limiting the use of neurocognitively active medications may help decrease excess rates of delirium, especially among PWH.

Thioredoxin Interacting Protein Inhibitors In Diabetes Mellitus A Critical Review.

Diabetes Mellitus (DM)is one of the highest contributors to global mortality, exceeding numbers of even the three major infectious diseases in the world, namely Tuberculosis, HIV AIDS, and Malaria. DM is characterised by increased serum levels of glucose caused by a loss of beta cells of the pancreatic islets, responsible for the secretion of insulin. Upon accumulation of data via a wide array of literature surveys, it has been found that Thioredoxin Interacting Protein (TXNIP)presents itself as a vital factor in controlling the production and loss of beta islet cells. TXNIP inhibits the action of the Thioredoxin TRX protein found in the beta cells thereby rendering it ineffective in maintaining the cellular redox balance causing oxidative stress and subsequent consequences ultimately leading to aggravation of the disease. TRX exists in the form of two isoforms - TRX1, which is located in the cytosol and at times translocate to the nucleus, and TRX2, which is located in the nucleus. TRX is responsible for the maintenance of the normal cellular redox balance by reducing the oxidised proteins formed by the Reactive Oxygen Species (ROS)with the help of NADPH dependant TRX Reductase enzyme. This proves to be essential in the pathogenesis of Diabetes Mellitus as the beta cells of the pancreatic islets lack a sufficient amount of antioxidant systems. Thus, inhibition of TXNIP has become essential in the survival of beta cells, not only enhancing insulin secretion and sensitivity but also alleviating the diseases associated with Diabetes. Hence, TXNIP is discovered to be a unique therapeutic target in the management of DM.

Predictors of HIV Molecular Cluster Membership and Implications for Partner Services.

Public health surveillance data used in HIV molecular cluster analyses lack contextual information that is available from partner services data. Integrating these data sources in retrospective analyses can enrich understanding of the risk profile of people in clusters. In this study, HIV molecular clusters were identified and matched to information on partners and other information gleaned at the time of diagnosis, including co-infection with syphilis. We aimed to produce a more complete understanding of molecular cluster membership in Houston, Texas, a city ranking ninth nationally in rate of new HIV diagnoses that may benefit from retrospective matched analyses between molecular and partner services data to inform future intervention. Data from partner services were matched to molecular HIV records of people newly diagnosed from 2012-2018. By conducting analyses in HIV-TRACE using viral genetic sequences, molecular clusters were detected. Multivariable logistic regression models were used to estimate the association between molecular cluster membership and completion of a partner services interview, number of named partners, and syphilis co-infection. Using data from 4,035 people who had a viral genetic sequence and matched partner services records, molecular cluster membership was not significantly associated with completion of a partner services interview. Among those with sequences who completed a partner services interview (n3,869), 45.3% (n1,753) clustered. Molecular cluster membership was significantly associated with naming 1 or 3 partners compared to not naming any partners (adjusted odds ratio (aOR) 1.27 95% CI 1.08, 1.50, P0.003 and aOR 1.38 95% CI 1.06, 1.81, P0.02). Alone, co-infection with syphilis was not significantly associated with molecular cluster membership. Syphilis co-infection was associated with molecular cluster membership when coupled with incarceration (aOR 1.91 95% CI 1.08, 3.38, P0.03), a risk for treatment interruption. Enhanced intervention among those with similar profiles, such as people co-infected with other risks, may be warranted.

Alcohol use, suicidality and virologic non-suppression among young adults with perinatally acquired HIV in Thailand a cross-sectional study.

Young adults with perinatally acquired HIV (YA-PHIV) are facing transitions to adult life. This study assessed health risk behaviours (including substance use), mental health, quality of life (QOL) and HIV treatment outcomes of Thai YA-PHIV. A cross-sectional study was conducted in Thai YA-PHIV aged 18-25 years who were enrolled in a prospective cohort study at five tertiary paediatric HIV care centres in Thailand. Study data were obtained through face-to-face interviews from November 2020 to July 2021. Assessments were performed for alcohol use (Alcohol Use Disorders Identification Test AUDIT), smoking (Fagerstrom Test for Nicotine Dependence), drugsubstance use (Drug Abuse Screening Test DAST-10), depression (Patient Health Questionnaire for Adolescents PHQ-A), anxiety (Generalized Anxiety Disorder GAD-7) and QOL (World Health Organization QOL Brief-Thai). HIV treatment outcomes were extracted from the National AIDS Program database. Of 355 YA-PHIV, 163 (46%) were males their median age was 21.7 (interquartile range, IQR 20.2-23.5) years. There were 203 YA-PHIV (58%) who reported ever having sex 141 (40%) were sexually active in the past 6 months, of whom 86 (61%) reported 100% condom use. Overall, 49 (14%) met the criteria for harmful alcohol use 28 (7.9%) were alcohol dependent. Sixty (17%) were current smokers and 37 (11%) used drugssubstances. The frequency of moderate up to severe symptoms for depression was 18% and for anxiety was 9.7%. Their overall QOL was good in 180 (51%), moderate in 168 (47%) and poor in five (1.4%). There were 49 YA-PHIV (14%) with CD4 <200 cellsmm Regular screening for alcohol use and mental health, including suicidality, would be useful to identify YA-PHIV who need more intensive psychosocial support or referral services to ensure they can achieve and maintain a high QOL into adult life.

Cost-effectiveness of screening and treating anal pre-cancerous lesions among gay, bisexual and other men who have sex with men living with HIV.

Gay, bisexual and other men who have sex with men (GBM) living with HIV have a substantially elevated risk of anal cancer (85 cases per 100,000 person-years vs 1-2 cases per 100,000 person-years in the general population). The precursor to anal cancer is high-grade squamous intraepithelial lesion (HSIL). Findings regarding the cost-effectiveness of HSIL screening and treatment in GBM are conflicting. Using recent data on HSIL natural history and treatment effectiveness, we aimed to improve upon earlier models. We developed a Markov cohort model populated using observational study data and published literature. Our study population was GBM living with HIV aged ≥35 years. We used a lifetime horizon and framed our model on the Australian healthcare perspective. The intervention was anal HSIL screening and treatment. Our primary outcome was the incremental cost-effectiveness ratio (ICER) as cost per quality-adjusted life-year (QALY) gained. Anal cancer incidence was estimated to decline by 44-70% following implementation of annual HSIL screening and treatment. However, for the most cost-effective screening method assessed, the ICER relative to current practice, Australian Dollar (AUD) 135,800 per QALY gained, remained higher than Australias commonly accepted willingness-to-pay threshold of AUD 50,000 per QALY gained. In probabilistic sensitivity analyses, HSIL screening and treatment had a 20% probability of being cost-effective. When the sensitivity and specificity of HSIL screening were enhanced beyond the limits of current technology, without an increase in the cost of screening, ICERs improved but were still not cost-effective. Cost-effectiveness was achieved with a screening test that had 95% sensitivity, 95% specificity, and cost ≤ AUD 24 per test. Establishing highly sensitive and highly specific HSIL screening methods that cost less than currently available techniques remains a research priority. No specific funding was received for this analysis.

Prospects for tuberculosis elimination in Ethiopia feasibility, challenges, and opportunities.

To end the global tuberculosis (TB) epidemic and eliminate TB, countries around the world committed to significantly expanding the scope of their efforts, including rapid uptake of new tools, interventions, and strategies, and envisioned a world free of TB. Between 2010 and 2020, Ethiopia experienced a 5% average annual decline in TB incidence. However, at that current rate, ending the TB epidemic (<10 TB cases100,000 population) may not be possible soon. As a high TB and TBHIV burden country, Ethiopias TB epidemic is characterized by a high rate of transmission in the general population and hard-to-reach areas and progression of latent TB infection (LTBI) rather than cross-border migration. Studies suggest that a combination of interventions, such as intensive household screening with TB preventive therapy, has the potential to significantly decrease the incidence of TB. The feasibility of reducing the population-level TB incidence by a combination of interventions in Ethiopia is unknown. Based on the World Health Organizations TB elimination framework and the END TB strategic documents and previously published reviews in TB elimination we conducted a narrative review to summarize and estimated the effect of a combined intervention package (community-based TB screening for active case finding and TB and LTBI prevention and treatment among high-risk groups like household and close contacts). The projected annual decline of TB incidence was above 16%. With this level of impact and nationwide scale-up of the interventions, Ethiopia aligns well with ending the TB epidemic before 2035 and shifting toward TB elimination in the foreseeable future. In the Ethiopia setting, we recommend future studies generating evidence on the impact of the combination intervention package to reduce TB incidence in Ethiopia, which is aiming to shift from control to TB elimination.

Burden of hypertension and associated factors among HIV-positive adults in Busia County, Kenya.

the use of antiretroviral (ARVs) for the management of HIV (human immunodeficiency virus) infection has resulted in a prolonged lifespan among HIV-positive individuals. Both HIV infection and ARVs treatment put this population at a greater risk of developing hypertension. The study aimed at establishing the burden of hypertension and associated factors among HIV-positive population. a cross-sectional design was employed where a total of 280 HIV-positive adults in Busia County were selected in a multi-stage sampling procedure between March and August 2020. Sociodemographic, economic and behavioral information was collected using a structured questionnaire. Anthropometric measurements were taken using standard methods while clinical data were extracted from patients´ medical records. Proportion was used to establish hypertension burden. Analyses were done using the T-test, Chi-square, and odds ratio. among the 280 study participants, 194 (69.3%) were females, and 239(85.4%) over 35 years of age. Hypertensive cases were 55 (19.6%). The hypertensive group had a significantly higher mean age (52.25±10.4 vs 44.9±11.3 p0.002), waist-to-hip ratio (0.93±0.09 vs 0.89±0.07 p0.016), HIV duration (8.64±4.63 vs 6.86±4.04 p0.014) and cumulative ART treatment duration (8.31±4.61 vs 6.68±3.93 p0.018). Factors found to be significantly associated with hypertension in the bivariate analysis included age (p0.003) family history (p0.024) duration of alcohol intake (p0.034) HIV duration (p0.033) and treatment duration (p0.043). In the multivariate analysis, only age (p0.045) and family history (p0.018) contributed significantly in the logistic regression model. the study revealed a slightly lower burden of hypertension among HIV -positive adults in Busia County. Age and family history were the factors independently associated with hypertension in this study.

Predictors of Viral Load Status Over Time Among HIV Infected Adults Under HAART in Zewditu Memorial Hospital, Ethiopia A Retrospective Study.

HIV attacks the CD4 cells which are responsible for the bodys immune response to infectious agents. The main objective of this study was to identify predictors of viral load status over time among HIV patients under HAART in Zewditu Memorial Hospital. A retrospective institutional-based cohort study design was conducted on 161 HIV-infected adults under HAART whose follow-ups were from January 2014 up to December 2017. A generalized linear mixed-effects model was conducted to infer predictors of the status of viral load at 95% of CI). The descriptive statistics revealed that about 55.9% of the adults under treatment had a detected viral load status. Among the potential predictors, visiting time of patients (AOR 0.731, 95% (0.634,0.842) and p-value <0.01), age of patients (AOR 1.0666, 95% CI (1.0527,1.0917) and p-value <0.01), weight (AOR. 0.904, 95% CI (0.862, 0.946) and p-value <0.01), baseline CD4 cell count (AOR 0.996, 95% CI (0.994, 0.998) and P-value <0.01), educated patients (AOR 0.030, 95% CI (0.002, 0.385) and p-value0.0053), rural patients (AOR 6.30,95% CL (1.78, 2.25) and p-value0.0043), working status patients (AOR 0.5905, 95% CI (0.547,0.638), p-value <0.01), poor adherent patients (AOR 1.120, 95% CI (1.035,1.391) and p-value 0.016) and patients disclosed the disease status (AOR 0.195, 95% CI (0.023, 0.818) and p-value0.0134) significantly affected the detection status of viral loads, keeping all other covariates constant. The predictor variables visiting times, the weight of patients, residence area, age of patients, educational level, clinical stages, functional status, baseline CD4 cell count, adherence status, and disclosure status of the disease statistically and significantly affected the status of viral load. Hence, health-related education should be given for patients to disclose their disease status, to be good adherents based on the prescription given to the health staff. Due attentions should be given for rural and uneducated patients. Attention should be forwarded to for non-adherent patients to follow the instruction given by the health staff.

Multi-dimensional mismatch and barriers for promoting PrEP among men who have sex with men in China a cross sectional survey from the Demand-side.

Men who have sex with men (MSM) is a key population for preventing HIV in China, yet pre-exposure prophylaxis (PrEP) is not widely accepted in this population. The objective of this manuscript was to assessed the barriers in the acknowledgement and uptake focusing the demand side. An online questionnaire survey was conducted from December 2018 to January 2019. All participants were required to scan two-dimensional code which was the online crowdsourcing survey platform to complete the electronic questionnaire anonymously. Among 1915 MSM from thirty-four cities of China, 512 (26.7%) versus 1617 (84.4%) had an objective or subjective need of PrEP, respectively. One hundred and six (5.5%) reported affordability and only 23 (1.2%) had ever taken it. Age, living alone and occupation were associated with the objective needs. Age, income, sexual behavior were associated with actual usage. The participants who they had objective need to use PrEP are the population which we should focus on. A wide disconnect exists among the objective need, willingness, affordability and uptake of PrEP. Cost was the most prevalent barrier, accounting for 78.22% of individuals who needed and wished for PrEP but finally failed to receive it. The findings might facilitate optimizing future allocation of resources to better promote PrEP in Chinese MSM.

Pre-exposure prophylaxis (PrEP) for HIV prevention among people who inject drugs a global mapping of service delivery.

The World Health Organization (WHO) recommends oral pre-exposure prophylaxis (PrEP) for all people at substantial risk of HIV as part of combination prevention. The extent to which this recommendation has been implemented globally for people who inject drugs is unclear. This study mapped global service delivery of PrEP for people who inject drugs. Between October and December 2021, a desk review was conducted to obtain information on PrEP services for people who inject drugs from drug user-led networks and HIV, harm reduction, and human rights stakeholders. Websites of organizations involved in HIV prevention or services for people who inject drugs were searched. Models of service delivery were described in terms of service location, provider, and package. PrEP services were identified in 27 countries (15 high-income). PrEP delivery models varied within and across countries. In most services, PrEP services were implemented in healthcare clinics without direct links to other harm reduction services. In three countries, PrEP services were also provided at methadone clinics. In 14 countries, PrEP services were provided through community-based models (outside of clinic settings) that commonly involved peer-led outreach activities and integration with harm reduction services. This study indicates limited PrEP availability for people who inject drugs. There is potential to expand PrEP services for people who inject drugs within harm reduction programs, notably through community-based and peer-led services. PrEP should never be offered instead of evidence-based harm reduction programs for people who inject drugs however, it could be offered as an additional HIV prevention choice as part of a comprehensive harm reduction program.

Addressing key issues in HIV self-test program implementation for Black and Latino sexual minority men in the Southern United States a multiphase study protocol.

Black and Latino sexual minority men in the Southern United States have the highest HIV infection rates in the country. Increased HIV testing can help decrease onward HIV transmission through detecting previously undiagnosed infections. HIV self-testing is an evidence-based strategy to increase HIV testing among sexual minority men, but the implementation of this intervention in the Southern United States is limited. One implementation barrier is the lack of knowledge of Black and Latino sexual minority mens preferences for various HIV self-testing program characteristics and their willingness to pay for these preferences. In addition, little is known about facilitators and barriers to initiating HIV self-testing programs from the perspectives of HIV prevention implementation decision-makers in this region. We will conduct an online discrete choice experiment among Black and Latino sexual minority men in the Southern United States (n 300) to estimate this populations preferences for the following HIV self-testing program characteristics delivery strategy (home delivery, peer delivery, clinic pickup) delivery speed (same day, next day, 3 days, and 5 days) support (instructions only, during test, and 1 week after delivery) and price ($0, $20, $40, $50, $60). We will also use this choice data to generate willingness-to-pay estimates for each program characteristic. Guided by the Consolidated Framework for Implementation Research, we will then conduct semi-structured interviews (n 30) with HIV prevention program decision-makers at various health organizations serving Black and Latino sexual minority men in the region to further understand facilitators and barriers to implementation of the most preferred HIV self-testing program design. By gaining perspectives on HIV self-testing implementation from patients and providers, this project will build a roadmap for the initiation of HIV self-testing programs to decrease HIV incidence among one of the most disproportionately impacted populations in the USA.

Identifying the needs of older people living with HIV (≥ 50 years old) from multiple centres over the world a descriptive analysis.

Older People Living with HIV (OPWH) combine both aging and HIV-infection features, resulting in ageism, stigma, social isolation, and low quality of life. This context brings up new challenges for healthcare professionals, who now must aid patients with a significant comorbidity burden and polypharmacy treatments. OPWH opinion on their health management is hardly ever considered as a variable to study, though it would help to understand their needs on dissimilar settings. We performed a cross-sectional, comparative study including patients living with HIV aged ≥50 years old from multiple centers worldwide and gave them a survey addressing their perception on overall health issues, psychological problems, social activities, geriatric conditions, and opinions on healthcare. Data was analyzed through Chisquared tests sorting by geographical regions, age groups, or both. We organized 680 participants data by location (Center and South America CSA, Western Europe WE, Africa, Eastern Europe and Israel EEI) and by age groups (50- 55, 56-65, 66-75, >75). In EEI, HIV serostatus socializing and reaching undetectable viral load were the main problems. CSA participants are the least satisfied regarding their healthcare, and a great part of them are not retired. Africans show the best health perception, have financial problems, and fancy their HIV doctors. WE is the most developed region studied and their participants report the best scores. Moreover, older age groups tend to live alone, have a lower perception of psychological problems, and reduced social life. Patients opinions outline region- and age-specific unmet needs. In EEI, socializing HIV and reaching undetectable viral load were the main concerns. CSA low satisfaction outcomes might reflect high expectations or profound inequities in the region. African participants results mirror a system where general health is hard to achieve, but HIV clinics are much more appealing to them. WE is the most satisfied region about their healthcare. In this context, age-specific information, education and counseling programs (i.e. Patient Reported Outcomes, Patient Centered Care, multidisciplinary teams) are needed to promote physical and mental health among older adults living with HIVAIDS. This is crucial for improving health-related quality of life and patients satisfaction.

Physical-mental health and awareness of HIVSTIs among men who have sex with men in selected cities of India.

Men who have Sex with Men being sexual minorities are a vulnerable section of society and are at greater risk of ill-treatment if they are out of the closet regarding their sexuality. Previous evidence suggests that they experienced heightened susceptibility to physical and mental illnesses owing to widespread discrimination and victimization across different walks of life, particularly in developing countries. However, there is a paucity of sound data and scientific understanding related to linkages between physical-mental health and awareness about Human Immunodeficiency VirusSexually Transmitted Infections among Men who have Sex with Men in the Indian context. Using a mixed-method approach, the present study examined the association between physical-mental well-being and awareness of comprehensive Human Immunodeficiency VirusSexually Transmitted Infectionsrelevant health behaviours based on primary data collected from 300 respondents from six selected metro cities in India. Descriptive statistics, chi-square test and binary logistic regression model have been used for the quantitative data analyses. In-depth interviews were conducted to contextualize and appreciate the substantive meanings and significance coming out from the quantitative results with the lived experiences of the study respondents. Finding suggests that one-fourth of the respondents were experiencing long-term illnesses while close to four out of ten respondents experienced short-term illnesses. About one-third of the respondents experienced disordered eating behaviour and mood swings. Close to one-fifth of the respondents reportedly contemplated suicidal thoughts. Awareness related to Sexually Transmitted Infections and preventive measures related to Human Immunodeficiency Virus risk was considerably low among Men who have Sex with Men. Awareness about sexual and reproductive health issues among Men who have Sex with Men needs to be strengthened to curtail the disproportionate risk and vulnerability of Human Immunodeficiency Virus and Sexually Transmitted Infections. The public healthcare system needs to be sensitized and upgraded to cater user-friendly quality healthcare services, without any discrimination against sexual minorities including Men who have Sex with Men. Furthermore, generating public awareness about gender and sexuality-related matters and reducing stigma and discrimination is critical for achieving the health-related sustainable development goals in India without leaving no one behind.

Heavily treatment-experienced people living with HIV in the OPERA® cohort population characteristics and clinical outcomes.

Multi-class resistance, intolerance, and drug-drug interactions can result in unique antiretroviral (ART) combinations for heavily treatment-experienced (HTE) people living with HIV (PLWH). We aimed to compare clinical outcomes between HTE and non-HTE PLWH. Eligible ART-experienced PLWH in care in the OPERA® Cohort were identified in a cross-sectional manner on December 31, 2016 and observed from the date of initiation of the ART regimen taken on December 31, 2016 until loss to follow up, death, study end (December 31, 2018), or becoming HTE (non-HTE group only). In the absence of resistance data, HTE was defined based on the ART regimens used (i.e., exposed to ≥ 3 core agent classes or regimen suggestive of HTE). Time to virologic undetectability, failure, and immunologic preservation were assessed using Kaplan-Meier methods cumulative probabilities were compared between the two groups. Regimen changes, incident morbidities, and death were described. A total of 24,183 PLWH (2277 HTE PLWH, 21,906 non-HTE) were followed for a median of 28 months (IQR 21, 38). Viremic HTE PLWH (viral load VL ≥ 50 copiesmL) were less likely to achieve undetectability (VL < 50 copiesmL 24-month cumulative probability 80% 95% Confidence Interval 77-82) than their non-HTE counterparts (85% 84-86). No difference was observed in the probability of maintaining VLs < 200 copiesmL over the first 48 months after achieving suppression (< 50 copiesmL). HTE PLWH were less likely than non-HTE PLWH to maintain CD4 cell counts ≥ 200 cellsµL (24-month cumulative probability 95% HTE 91-93 97% non-HTE 97-97), and more likely to change regimens (45% HTE 41% non-HTE). Incident non-AIDS defining event (ADE) morbidities were common in both populations, though more likely among HTE PLWH (45%) than non-HTE PLWH (35%). Incident ADE morbidities and deaths were uncommon among HTE (ADEs 5% deaths 2%) and non-HTE (ADEs 2% deaths 1%) PLWH. HTE PLWH were at greater risk of unfavorable treatment outcomes than non-HTE PLWH, suggesting additional therapeutic options are needed for this vulnerable population.

A Relationship-Focused HIV Prevention Intervention for Young Sexual Minority Men in the United States A Pilot Randomized Controlled Trial of the We Prevent Intervention.

We Prevent is a virtual counseling intervention designed to improve communication as a mechanism for reducing HIV risk among young sexual minority men (SMM) in relationships. We evaluated the feasibility, acceptability, and preliminary efficacy of We Prevent in comparison to standard Counseling, Testing, and Referral among a national sample of 318 SMM ages 15-24 in a pilot randomized control trial. We found significant differences in condomless sex with outside partners however, there were no differences in other sexual behaviors, sexual agreements, intimate partner violence (IPV), or communication between the conditions across the 9-month follow-ups. Stratified analyses found non-significant trends suggestive that We Prevent may reduce condomless sex for those ages 15-17 and for relationships over 1-year and may reduce IPV in relationships over 1-year. Though study retention was adequate, session attendance was low. Exit interviews participants reported benefits of We Prevent and provided insights into how to increase uptake.

Perspectives of people living with HIV and health workers about a point-of-care adherence assay a qualitative study on acceptability.

Current antiretroviral therapy (ART) adherence monitoring is premised on patients self-reported adherence behaviour (prone to recall error) and verified by blood viral load measurement (which can delay results). A newly developed Urine Tenofovir Rapid Assay (UTRA) assesses tenofovir in urine at point-of-care and is a novel tool to test and immediately respond to adherence levels of people living with HIV (PLHIV). We explored PLHIV and health workers initial perceptions about integrating the UTRA into routine medical care for adherence support. We conducted a series of once-off in-depth qualitative interviews with PLHIV (

Application of CAR-T cell technology in autoimmune diseases and human immunodeficiency virus infection treatment.

Chimeric antigen receptor (CAR) T-cell therapy is an immunotherapy approach that has played a tremendous role in the battle against cancer for years. Since the CAR T lymphocytes are unrestricted-major histocompatibility complex T lymphocytes, they could identify more targets than natural T cells, resulting in practical and widespread functions. The good prospects of CAR T-cell therapy in oncology can be additionally applied to treat other diseases such as autoimmune and infectious diseases. CAR-T cell-derived immunotherapy for autoimmune disorders can be allocated to CAR-Tregs and chimeric autoantibody receptor T cells. Other generations of CARs target human immunodeficiency virus (HIV) proteins. In this review, we summarize CAR-T cell therapies in autoimmune disorders and HIV infection.

Examining participant representation by sex, race, ethnicity and age in United States blood donation and blood transfusion clinical trials.

Significant inequities based on sex, race, ethnicity, and age exist among participants in clinical trials dedicated to investigating medical disease states. While general demographic data regarding blood donors and blood transfusion recipients have been studied extensively, the demographics of participants involved in blood donation and blood transfusion clinical trials are unknown. We performed a cross-sectional analysis of United States (U.S.) -based interventional blood donation and blood transfusion clinical trials registered with Clinicaltrials.gov to ascertain the composition of participants sex, race, ethnicity, and age, as well as diagnostic conditions and geographic trial locations.Eligible trials were undertaken between July 2003 and August 2020. Thirty-eight of the one hundred and fifty-two blood donation and blood transfusion clinical trials met inclusion criteria (seven blood donation and thirty-one blood transfusion trials). While the participant dataset from trial reports were incomplete, 100 % of blood donation trials reported sex and age, 71.4 % reported race, and 42.3 % reported ethnicity. 96.8 % of blood transfusion trials reported sex, 51.6 % reported race, 38.7 % reported ethnicity, and 100 % reported age. Among 2720 participants enrolled in the seven blood donation trials, females were underrepresented (28.5 %) compared to U.S. Census data. Conversely, female (50.8 %) and male participants (49.2 %) were equally represented in blood transfusion trials (9255 participants). White participants were overrepresented in blood donation trials (73.4 %), while Hispanic or Latinos were underrepresented in both blood donation (7.7 %) and blood transfusion (8.2 %) trials compared to 2019 U.S.Census data. Only 8.3 % of blood transfusion clinical trials open to adults reported including older adults (i.e., ≥ 65yo). Despite mandatory reporting requirements and an already established framework, researchers frequently failed to report complete demographics of blood donation and blood transfusion clinical trial participants. Furthermore, various demographic groups were underrepresented in blood donation andor blood transfusion clinical trials, including females, Hispanic or Latino individuals, and older adults. These findings demonstrate the need for implementation of strategies to ensure equitable representation of individuals in blood donation and transfusion clinical trials.

Sex. Maybe We Should Do Things to be Healthy About It. Adolescent-Caregiver Discussions About Sex.

Adolescents are disproportionately burdened with HIV. Numerous barriers limit adolescent pre-exposure prophylaxis (PrEP) use for HIV prevention. We explored adolescent-caregiver perspectives on discussing sexual health and PrEP to inform future caregiver interventions as a possible strategy to promote PrEP use. We conducted separate in-depth interviews with adolescents aged 14-18 living in Alabama and their parentguardian (caregiver). Interviews explored attitudes about sex, knowledge and attitudes about HIV prevention and PrEP, and attitudes about PrEP communication within adolescent-caregiver groups. Thematic analysis of adolescent and caregiver interviews was conducted independently and then triangulated to compare shared themes. Nine adolescents and seven caregivers contributed to five dyads and two triads. Adolescents had a median age of 16 years (range 14-18) five were girls (55%), and five were non-Hispanic Black (55%). Most caregivers were mothers (5, 71%), non-Hispanic Black (5, 71%), with a median age of 41 (36-56) years. All adolescents expressed willingness to involve their caregiver around PrEP use. Major themes included as follows 1) caregiver efforts to overcome cultural taboos about sex and sexuality foster adolescents willingness to talk with caregivers about sex 2) evolving societal norms and reflections on their own upbringings motivate caregivers to discuss and support adolescents with sexual health and 3) caregivers desire to engage in sexual health discussions with providers and support their teens with PrEP. As socio-cultural norms around sex evolve, adolescent-caregiver discussions about sexual health and PrEP may be an opportunity to increase PrEP use and reduce HIV infections among select adolescent sub-populations.

The effect of mobile phone utilization for enhanced adherence counselling intervention among persons with HIV.

The conduct of physical enhanced adherence counselling (EAC) for antiretroviral therapy (ART) non-adherers is often flawed by objectionable time lag from commencement to timely completion of the process. Therefore, we conducted a retrospective cohort study of 342 adults (≥18 years) with HIV on ART to determine the outcome of utilizing mobile phone based EAC intervention. Structural equation modelling framework, with full information maximum likelihood estimator was used to elucidate the pathways linking the relationship between individual characteristics, perceived barriers to ART adherence, and the applied interventions. A total of 321(93.9%) participants completed the required 3 EAC sessions over 60-days. The proportion of viral load (VL) re-suppression (<1000 copiesmL) after EAC intervention was 66.6%. The mean durations of EAC onset from time of high VL confirmation and completion of EAC were 6.26 ± 3.22 and 59.99 ± 5.14 days, respectively. In the simultaneous model (Comparative Fit Index 0.89, Tucker-Lewis Index 0.851, Root Mean Square (RMS) Error of Approximation 0.049, Standardized RMS Residual 0.059), the variables forgot, knowledgebeliefs, side effect of drugs, lostran out of drugs, scheduling, and stigma were significant barrier factors contributing to poor ART adherence. The use of mobile phones for EAC intervention was effective for early initiation and timely completion of the sessions.

Predicting and influencing PrEP use the role of motivational and attitudinal factors.

This study examined PrEP attitude and HIV risk factors associated with PrEP motivation and evaluated the efficacy of a mock public health video that addresses both motivational and stigma issues for improving PrEP uptake over a standard educational video. Gay, bisexual, and other men who have sex with men (GBMSM

An automated ultra-fast, memory-efficient, and accurate method for viral genome classification.

The classification of different organisms into subtypes is one of the most important tools of organism studies, and among them, the classification of viruses itself has been the focus of many studies due to their use in virology and epidemiology. Many methods have been proposed to classify viruses, some of which are designed for a specific family of organisms and some of which are more general. But still, especially for certain categories such as Influenza and HIV, classification is facing performance challenges as well as processing and memory bottlenecks. In this way, we designed an automated classifier, called PC-mer, that is based on k-mer and physicochemical characteristics of nucleotides, which reduces the number of features about 2

Elevated frequency and everyday functioning implications of vascular depression in persons with HIV disease.

Depression and cardiovascular disease are common and associated with one another in HIV disease. This study aimed to determine the frequency and everyday functioning implications of the clinical syndrome of vascular depression among people living with HIV (PLWH). Participants in this cross-sectional study included 536 PLWH and 272 seronegative individuals who completed a biomedical and psychiatric research evaluation. Vascular depression was operationalized as the current presence of 1) two or more vascular conditions and 2) depression as determined by a normative elevation on the DepressionDejection subscale of the Profile of Mood States or a diagnosis of Major Depressive Disorder per the Composite International Diagnostic Interview. Everyday functioning was measured by both self- and clinician-rated activities of daily living. A logistic regression model showed that HIV was associated with a three-fold increased risk of vascular depression, independent of potential confounding factors. A second logistic regression model within the PLWH sample showed that PLWH with vascular depression had significantly greater odds of dependence in everyday functioning as compared to PLWH with either vascular disease or depression alone. The elevated frequency of vascular depression in PLWH is consistent with the vascular depression hypothesis from the late-life depression literature. The high rate of functional dependence among PLWH with vascular depression highlights the clinical importance of prospective work on this syndrome in the context of HIV disease.

Gender-specific effects of COVID-19 lockdowns on scientific publishing productivity Impact and resilience.

The SARS-CoV2 pandemic led to drastic social restrictions globally. Early data suggest that women in science have been more adversely affected by these lockdowns than men, with relatively fewer scientific articles authored by women. However, these observations test broad populations with many potential causes of disparity. Australia presents a natural experimental condition where several states of similar demographics and disease impact had differing approaches in their social isolation strategies. The state of Victoria experienced 280 days of lockdowns from 2020 to 2021, whereas the comparable state of New South Wales experienced 107 days, most of these in 2021, and other states even fewer restrictions. To assess how the gender balance changed in Australian biomedical publishing with the lockdowns, we created a custom workflow to analyse PubMed data from more than 120,000 published articles submitted in 2019-2021 from Australian authors. Broadly, Australian women have been incredibly resilient to the challenges faced by the lockdowns. There was an increase in the number of published articles submitted in 2020 that was equally due to women as men, including from Victoria. On the other hand, articles specifically addressing COVID-19 were significantly less likely to be authored by women than those on other topics, a finding not likely due to particular gender imbalance in virology or viral epidemiology, since publications on HIV followed similar patterns to previous years. By 2021, this imbalance had reversed, with more COVID-19-related papers authored by women than men. These data suggest women from Victoria were less able to rapidly transition to new research early in the pandemic but had accommodated to the new conditions by 2021. This work indicates we need strategies to support women in science as the pandemic continues and to continue to monitor the situation for its impact on vulnerable groups.

Disease burden among Ukrainians forcibly displaced by the 2022 Russian invasion.

The Russian invasion of Ukraine on February 24, 2022, has displaced more than a quarter of the population. Assessing disease burdens among displaced people is instrumental in informing global public health and humanitarian aid efforts. We estimated the disease burden in Ukrainians displaced both within Ukraine and to other countries by combining a spatiotemporal model of forcible displacement with age- and gender-specific estimates of cardiovascular disease (CVD), diabetes, cancer, HIV, and tuberculosis (TB) in each of Ukraines 629 raions (i.e., districts). Among displaced Ukrainians as of May 13, we estimated that more than 2.63 million have CVDs, at least 615,000 have diabetes, and over 98,500 have cancer. In addition, more than 86,000 forcibly displaced individuals are living with HIV, and approximately 13,500 have TB. We estimated that the disease prevalence among refugees was lower than the national disease prevalence before the invasion. Accounting for internal displacement and healthcare facilities impacted by the conflict, we estimated that the number of people per hospital has increased by more than two-fold in some areas. As regional healthcare systems come under increasing strain, these estimates can inform the allocation of critical resources under shifting disease burdens.

Higher Dose Oral Fluconazole for the Treatment of AIDS-related Cryptococcal Meningitis (HIFLAC)-report of A5225, a multicentre, phase III, two-stage, dose-finding, safety, tolerability and efficacy randomised, amphotericin B-controlled trial of the AIDS Clinical Trials Group.

The WHO recommended 1200mgday of fluconazole (FCZ) in the induction phase of cryptococcal meningitis (CM) in HIV prior to 2018 in regions where amphotericin-B (AMB) was unavailable. A 2-stage AMB-controlled, dose-escalation study to determine the maximum tolerated dose and the safetyefficacy of an induction-consolidation strategy of higher doses FCZ (1200mg-2000mgday), adjusted for weight and renal function (eGFR)in adults with CM was undertaken. In Stage-1, three induction doses of FCZ (1200mgday, 1600mgday and 2000mgday) were tested in sequential cohortsand compared with AMB in a 31 ratio. A particular dose was not tested in Stage 2 if there were significant predetermined safety or efficacy concerns. In Stage-2, the 1200mg dose was excluded per protocol because of increased mortality, and participants were randomised to 1600mg, 2000mg FCZ or AMB in a 111 ratio. One hundred and sixty eight participants were enrolled with 48, 50, and 48 in the AMB, 1600mg and 2000mg cohorts. The Kaplan Meier proportion for mortality (90% CI) at 10 and 24 weeks for AMB was 17% (10, 29) and 24% (15, 37), compared to 20% (12, 32) and 30% (20, 43) for 1600mg, and 33% (23, 46) and 38% (27, 51) for 2000mgday FCZ. With the exception of a higher incidence of gastrointestinal side effects in the 2000mg cohort, both induction doses of FCZ were safe and well tolerated. There were no life-threatening changes in electrocardiogram QTc which were similar across all doses of FCZ and AMB. The median (IQR) change in log10 cryptoccal colony forming units (CFU) from week 0 to week 2 was -8(-4.1,-1.9) for AMB -2.5(-4.0, -1.4) for 1600mg FCZ and -8 (-3.2, -1.0) for 2000mg FCZ. The proportion (90% CI) CSF CM negative at 10 weeks was 81%(71,90) for AMB 56%(45,69) for 1600mg FCZ and 60%(49,73) for 2000mg FCZ. Induction phase weight and renal-adjusted doses of 1600mg and 2000mgday FCZ for CM were safe and well tolerated except for increased GI side effects in the 2000mgday dose, and had similar times to achieve CSF sterilization, but took significantly longer than AMB. The WHO recommended 1200mg FCZ was associated with a high mortality. While not statistically significant, mortality was numerically lower in the AMB compared to 1600mg and 2000mg FCZ These data make a case for a phase 3 study of higher doses of FZC.

HIV-1 release requires Nef-induced caspase activation.

HIV infection remains incurable to date and there are no compounds targeted at the viral release. We show here HIV viral release is not spontaneous, rather requires caspases activation and shedding of its adhesion receptor, CD62L. Blocking the caspases activation caused virion tethering by CD62L and the release of deficient viruses. Not only productive experimental HIV infections require caspases activation for viral release, HIV release from both viremic and aviremic patient-derived CD4 T cells also require caspase activation, suggesting HIV release from cellular viral reservoirs depends on apoptotic shedding of the adhesion receptor. Further transcriptomic analysis of HIV infected CD4 T cells showed a direct contribution of HIV accessory gene Nef to apoptotic caspases activation. Current HIV cure focuses on the elimination of latent cellular HIV reservoirs that are resistant to infection-induced cell death. This has led to therapeutic strategies to stimulate T cell apoptosis in a kick and kill approach. Our current work has shifted the paradigm on HIV-induced apoptosis and suggests such approach would risk to induce HIV release and thus be counter-productive. Instead, our study supports targeting of viral reservoir release by inhibiting of caspases activation.

Strengthening health systems capacity for linkage to HIV care for adolescent girls and young women and adolescent boys and young men in South Africa (SheSCap-Linkage) Protocol for a mixed methods study in KwaZulu-Natal, South Africa.

Adolescent girls and young women (AGYW) aged 15-24 years and adolescent boys and young men (ABYM) aged 15-34 years represent one of the populations at highest risk for HIV-infection in South Africa. The National Department of Health adopted the universal test and treat (UTT) strategy in 2016, resulting in increases in same-day antiretroviral therapy initiations and linkage to care. Monitoring progress towards attainment of South Africas 95-95-95 targets amongst AGYW and ABYM relies on high quality data to identify and address gaps in linkage to care. The aim of this study is to describe the current approaches for engaging AGYW and ABYM in the treatment continuum to generate knowledge that can guide efforts to improve linkage to, and retention in, HIV care among these populations in KwaZulu-Natal, South Africa. This is a mixed methods study, which will be conducted in uMgungundlovu district of KwaZulu-Natal, over a 24-month period, in 22 purposively selected HIV testing and treatment service delivery points (SDPs). For the quantitative component, a sample of 1100 AGYW aged 15-24 years and ABYM aged 15-35 years old will be recruited into the study, in addition to 231 healthcare providers (HCPs) involved in the implementation of the UTT program. The qualitative component will include 30 participating patients who were successfully linked to care, 30 who were not, and 30 who have never tested for HIV. Key informant interviews will also be conducted with 24 HCPs. Logistic regression will be used to model the primary outcomes on SDP types, while a time to event analysis will be conducted using a Cox regression model and adjusting the standard errors of the hazard ratio for the clustering of participants within SDPs. For qualitative data, a general inductive approach of analysis will be used. Findings from the study will be communicated to the study population and results will be presented to stakeholders and at appropriate local and international conferences. Outputs will also include a policy brief, peer reviewed journal articles and research capacity building through research degrees.

Prevalence of HIV seropositive status and associated factors among family members of index cases of antiretroviral clinical attendants in Sodo Town, Southern Ethiopia.

Human immunodeficiency virus is primarily transmitted through sexual contact with an infected partner and babies born to mothers infected with the virus. Partners of people living with HIV and children whose parents have HIV are at higher risk of contracting HIV unless they take preventive measures. This study aimed at identifying prevalence and determinants of HIV infection among family members of index cases on antiretroviral treatment (ART). A community-based cross-sectional study was conducted among 623 randomly selected family members of HIV index cases in Sodo Town from February to June 2021. A pre-tested structural questionnaire was used to collect data. Binary logistic regression was used to identify variables independently associated with the outcome variable. The adjusted odds ratio (AOR) with 95% confidence interval (CI) was used to show the strength of association, and a P-value 0.05 was used as a cut-off point to determine the level of statistical significance of point estimate. This study revealed that 31.5% (95%CI 27.6-35.2%) of family members of index cases were HIV seropositive. In subgroup analysis, this study also revealed that 11.1% (95%CI 8.4-14.5%) of biological children and 69.6% (95%CI 63.1-75.6%) of spousal partners of index cases were HIV seropositive. Immediate ART initiation of index cases (AOR 0.148, 95%CI 0.067-0.325), being bedridden or ambulatory functional status at enrollment (AOR 7.71, 95%CI 3.5-17), and baseline CD4 level of 350 cellsml (AOR 8.06, 95%CI 1.8-36) were statistically significant with the outcome variable among biological children. Among spousal partners, STI history or symptoms (AOR 5.7, 95%CI 1.86-17.5), early disclosure (AOR 0.062, 95%CI 0.024-0.159), immediate ART initiation (AOR 0.172, 95%CI 0.044-0.675), and duration of infection (AOR 5.09, 95%CI 1.8-14.4) were statistically associated with the outcome variable. As evidenced by our data, the risk of HIV among family members of index cases is high. Interventions like immediate ART initiation, early disclosure, screening, and early treatment of STIs for minimizing HIV transmission might be given.

Variation in missed doses and reasons for discontinuation of anti-tuberculosis drugs during hospital treatment for drug-resistant tuberculosis in South Africa.

Updated World Health Organization (WHO) treatment guidelines prioritize all-oral drug-resistant tuberculosis (DR-TB) regimens. Several poorly tolerated drugs, such as amikacin and para-aminosalicylic acid (PAS), remain treatment options for DR-TB in WHO-recommended longer regimens as Group C drugs. Incomplete treatment with anti-TB drugs increases the risk of treatment failure, relapse, and death. We determined whether missed doses of individual anti-TB drugs, and reasons for their discontinuation, varied in closely monitored hospital settings prior to the 2020 WHO DR-TB treatment guideline updates. We collected retrospective data on adult patients with microbiologically confirmed DR-TB between 2008 and 2015 who were selected for a study of acquired drug resistance in the Western Cape Province of South Africa. Medical records through mid-2017 were reviewed. Patients received directly observed treatment during hospitalization at specialized DR-TB hospitals. Incomplete treatment with individual anti-TB drugs, defined as the failure to take medication as prescribed, regardless of reason, was determined by comparing percent missed doses, stratified by HIV status and DR-TB regimen. We applied a generalized mixed effects model. Among 242 patients, 131 (54%) were male, 97 (40%) were living with HIV, 175 (72%) received second-line treatment prior to first hospitalization, and 191 (79%) died during the study period. At initial hospitalization, 134 (55%) patients had Mycobacterium tuberculosis with resistance to rifampicin and isoniazid (multidrug-resistant TB MDR-TB) without resistance to ofloxacin or amikacin, and 102 (42%) had resistance to ofloxacin andor amikacin. Most patients (129 53%) had multiple hospitalizations and DST changes occurred in 146 (60%) by the end of their last hospital discharge. Incomplete treatment was significantly higher for amikacin (18%), capreomycin (18%), PAS (17%) and kanamycin (16%) than other DR-TB drugs (P<0.001), including ethionamide (8%), moxifloxacin (7%), terizidone (7%), ethambutol (7%), and pyrazinamide (6%). Among the most frequently prescribed drugs, second-line injectables had the highest rates of discontinuation for adverse events (range 0.56-1.02 events per year follow-up), while amikacin, PAS and ethionamide had the highest rates of discontinuation for patient refusal (range 0.51-0.68 events per year follow-up). Missed doses did not differ according to HIV status or anti-TB drug combinations. We found that incomplete treatment for second-line injectables and PAS during hospitalization was higher than for other anti-TB drugs. To maximize treatment success, interventions to improve person-centered care and mitigate adverse events may be necessary in cases when PAS or amikacin (2020 WHO recommended Group C drugs) are needed.

Moderators of LGBQ-affirmative cognitive behavioral therapy ESTEEM is especially effective among Black and Latino sexual minority men.

Lesbian, gay, bisexual, and queer (LGBQ)-affirmative cognitive behavioral therapy (CBT) focused on minority stress processes can address gay and bisexual mens transdiagnostic mental and behavioral health concerns. Identifying moderators of treatment outcomes may inform the mechanisms of LGBQ-affirmative CBT and subpopulations who may derive particular benefit. Data were from a clinical trial in which gay and bisexual men with mental and behavioral health concerns were randomized to receive Effective Skills to Empower Effective Men (ESTEEM an LGBQ-affirmative transdiagnostic CBT Racialethnic minority identification, namely as Black or Latino, was the only statistically significant moderator of treatment efficacy ( Black and Latino gay and bisexual men experiencing comorbid mental and behavioral health risks might particularly benefit from a minority stress-focused LGBQ-affirmative CBT. Future research should identify mechanisms for this moderation to inform targeted treatment delivery and dissemination. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Heroin use and neuropsychological impairments comparison of intravenous and inhalational use.

Injection and inhalational heroin use are associated with different levels of brain exposure to heroin and its metabolites and differences in the severity of dependence, which might lead to differential impacts on neuropsychological functions. We examined the difference and the magnitude of difference in the neuropsychological functions between inhalational and injection heroin-dependent subjects and also compared them with healthy controls. The study sample comprised three groups 73 subjects with injection heroin dependence, 74 with inhalational heroin dependence, and 75 healthy controls (HC). We excluded patients with HIV, head injury, epilepsy, and severe mental illness. Neuropsychological assessments were done by Standard Progressive Matrices, Wisconsin Card Sorting Test (WCST), Iowa Gambling Task, Trail-Making Tests A and B (TMT), and Verbal and Visual Memory 1 and 2 Backtests (NBT). We estimated independent effects of the groups on various neuropsychological test parameters, adjusted for age and duration of dependence. In the WCST, the inhalational heroin-dependent group took more trials to complete the first category and had higher scores in the failure to maintain set than controls. The intravenous group had higher total errors than controls in verbal working memory tests and Visual Working Memory 2 Backtest. This group scored higher commission errors in the Verbal 2 Backtest than the controls. The two groups of heroin users differed in failure to maintain set and Verbal Working Memory 2 Backtests. The effect sizes of the group differences were modest. Either route of heroin use is associated with cognitive impairments inhalational and injection use involve different cognitive domains.

Persons with HIV Develop Spike-Specific Lymph Node Germinal Center Responses following SARS-CoV-2 Vaccination.

COVID-19 disproportionately affects persons with HIV (PWH) in worldwide locations with limited access to SARS-CoV-2 vaccines. PWH exhibit impaired immune responses to some, but not all, vaccines. Lymph node (LN) biopsies from PWH demonstrate abnormal LN structure, including dysregulated germinal center (GC) architecture. It is not clear whether LN dysregulation prevents PWH from mounting Ag-specific GC responses in the draining LN following vaccination. To address this issue, we longitudinally collected blood and draining LN fine needle aspiration samples before and after SARS-CoV-2 vaccination from a prospective, observational cohort of 11 PWH on antiretroviral therapy 2 who received a two-dose mRNA vaccine series and 9 who received a single dose of the Ad26.COV2.S vaccine. Following vaccination, we observed spike-specific Abs, spike-specific B and T cells in the blood, and spike-specific GC B cell and T follicular helper cell responses in the LN of both mRNA vaccine recipients. We detected spike-specific Abs in the blood of all Ad26.COV2.S recipients, and one of six sampled Ad26.COV2.S recipients developed a detectable spike-specific GC B and T follicular helper cell response in the draining LN. Our data show that PWH can mount Ag-specific GC immune responses in the draining LN following SARS-CoV-2 vaccination. Due to the small and diverse nature of this cohort and the limited number of available controls, we are unable to elucidate all potential factors contributing to the infrequent vaccine-induced GC response observed in the Ad26.COV2.S recipients. Our preliminary findings suggest this is a necessary area of future research.

Characterization of Megabat-Favored, CA-Dependent Susceptibility to Retrovirus Infection.

The isolation of the Koala retrovirus-like virus from Australian megabats and the identification of endogenous retroviruses in the bat genome have raised questions on bat susceptibility to retroviruses in general. To answer this, we studied the susceptibility of 12 cell lines from 11 bat species to four well-studied retroviruses (human and simian immunodeficiency viruses HIV and SIV and murine leukemia viruses B- and N-MLV). Systematic comparison of retroviral susceptibility among bats revealed that megabat cell lines were overall less susceptible to the four retroviruses than microbat cell lines, particularly to HIV-1 infection, whereas lineage-specific differences were observed for MLV susceptibility. Quantitative PCR of reverse transcription (RT) products, infection in heterokaryon cells, and point mutation analysis of the capsid (CA) revealed that (i) HIV-1 and MLV replication were blocked at the nuclear transport of the pre-integration complexes and before andor during RT, respectively, and (ii) the observed lineage-specific restriction can be attributed to a dominant cellular factor constrained by specific positions in CA. Investigation of bat homologs of the three previously reported post-entry restriction factors constrained by the same residues in CA, tripartite motif-protein 5α (TRIM5α), myxovirus resistance 2B (Mx2MxB), and carboxy terminus-truncated cleavage and polyadenylation factor 6 (CPSF6-358), demonstrated poor anti-HIV-1 activity in megabat cells, whereas megabat TRIM5α restricted MLV infection, suggesting that the major known CA-dependent restriction factors were not dominant in the observed lineage-specific susceptibility to HIV-1 in bat cells. Therefore, HIV-1 susceptibility of megabat cells may be determined in a manner distinct from that of primate cells.

Differences in Immune Responses in Individuals of Indian and European Origin Relevance for the COVID-19 Pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, large differences in susceptibility and mortality due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported between populations in Europe and South Asia. While both host and environmental factors (including Mycobacterium bovis BCG vaccination) have been proposed to explain this, the potential biological substrate of these differences is unknown. We purified peripheral blood mononuclear cells from individuals living in India and the Netherlands at baseline and 10 to 12 weeks after BCG vaccination. We compared chromatin accessibility between the two populations at baseline, as well as gene transcription profiles and cytokine production capacities upon stimulation. The chromatin accessibility of genes important for adaptive immunity was higher in the Indians than in the Europeans, while the latter had more accessible chromatin regions in genes of the innate immune system. At the transcriptional level, we observed that the Indian volunteers displayed a more tolerant immune response to stimulation, in contrast to a more exaggerated response in the Europeans. BCG vaccination strengthened the tolerance program in the Indians but not in the Europeans. These differences may partly explain the different impact of COVID-19 on the two populations.

Acute retroviral syndrome is associated with lower CD4 nadir and delayed viral suppression, which are blunted by immediate ART initiation.

To describe the prevalence of acute retroviral syndrome (ARS) and associated findings during primary HIV, and explore the relationship of ARS to clinical, virological, and immunological outcomes within a longitudinal screen, retest and treat study that minimized ascertainment bias. We evaluated ARS symptoms among 216 persons with acute and early incident HIV within the Sabes study of timing of antiretroviral therapy (ART) initiation during primary HIV in Peru. We evaluated patient reported symptoms and exam findings during primary HIV and used logistic regression and generalized linear models to evaluate associations with CD4 and CD8 T cell counts, HIV viral load, and a panel of 23 soluble markers of immune activation. 61% of participants had at least one ARS finding and 35% had at least 3. More ARS findings were reported in those enrolled within a month of estimated date of detectable infection (EDDI). Having more ARS signssymptoms was associated with increased risk of CD4 decrease below 350 cellsmL within the first 24 weeks, failure to suppress HIV viral load, and was most strongly associated with elevated IP-10. Immediate ART blunted effects on symptoms, CD4 and viral load, as associations were strongest in the arm that started ART after 24 weeks. Detrimental associations of ARS with CD4 counts, and CD4CD8 ratio were not maintained at 2 or 4 years. ARS has marked associations with short-term immunologic function and virologic suppression, which were mitigated in participants randomized to initiate ART immediately during primary infection.

Lower T cell response against SARS-CoV-2 variants of concern after mRNA vaccine and risk of breakthrough infections in people living with HIV.

We evaluated T-cell immune responses against SARS-CoV-2 variants of concern (VOC) after vaccination in people living with HIV (PWH), and their impact on the incidence of disease. Prospective cohort study. Peripheral blood mononuclear cells (PBMCs) were collected a median of 53 days after second dose of mRNA vaccine. Humoral response and T cell responses against the spike (S) glycoprotein of wild type SARS-CoV-2 (ancestral Wuhan variant) and mutated S-protein regions found in the Delta and Omicron variants were assessed by flow cytometry analysis. In 142 PWH without preceding SARS-CoV-2 infection, bivariate correlations showed a close association between T-cell responses to the different variants. However, despite at least 70% of PWH had cellular immune response to any variant, CD4 and CD8 T cell responses against VOC were lower in frequency and magnitude (-3% and -20% for Delta, -33% and -28% for Omicron variant) compared to that observed against the Wuhan strain. A higher magnitude of SARS-CoV-2 spike-specific CD8T cell responses against all the variants was observed in those PWH with greater immune reconstitution. Notably, 27 symptomatic breakthrough infections (19%) in the setting of Delta and Omicron transmission were observed during follow-up, associated with a significant lower humoral and T-cell response to ancestral strain and VOC. On the other hand, only 1 PWH with COVID-19 (4%) required hospitalization. A blunted T-cell response against Delta and Omicron variant is observed in PWH who received two doses of mRNA vaccine. This lower immune response is associated with breakthrough SARS-CoV-2 infections.

Viral suppression among adults with HIV receiving routine dolutegravir-based antiretroviral therapy and 3HP.

We aimed to evaluate safety of 3 months weekly isoniazid-rifapentine (3HP) for tuberculosis (TB) prevention when co-administered with dolutegravir-based antiretroviral therapy (TLD), and compare viral suppression among those initiating TLD3HP vs. TLD alone. We analyzed data from an ongoing Phase 3 randomized trial comparing TB screening strategies among adults with CD4≤350 cellsμL initiating routine antiretroviral therapy (ART) in Kampala, Uganda. TB screen-negative participants without contraindications are referred for self-administered 3HP. HIV viral load is routinely measured at six- and twelve-months. Here, we included TB-negative participants who initiated TLD with or without 3HP. We determined the number who discontinued 3HP due to drug toxicity. In addition, we assessed viral suppression at 6- and 12-months and used log-binomial regression to assess risk of viremia at 6-months for participants who initiated TLD3HP vs. TLD alone. Of 453 participants initiating TLD (287 63.4% female, median age 30 years IQR 25-37, median pre-ART CD4 count 188 cellsμL IQR 86-271), 163 (36.0%) initiated 3HP. Of these, 154 (94.5%) completed 3HP and one (0.6%) had treatment permanently discontinued due to a possible 3HP-related adverse event. At 6-months, for participants who received TLD3HP, risk of viremia >50 copiesmL was 1.51 (95% CI 1.07-2.14) times that of participants who received TLD alone. There was no difference in viral suppression between those who received TLD3HP vs. TLD alone at 12-months. Co-administration of TLD3HP was well-tolerated. However, those who received TLD3HP were less likely to achieve viral suppression within six-months compared to those who received TLD alone.