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36,826,983
Desires for Individual- and Interpersonal-Level Patient Portal Use for HIV Prevention Among Urban Sexual Minority Men Cross-sectional Study.
Gay, bisexual, and other sexual minority men have expressed the acceptability of patient portals as tools for supporting HIV prevention behaviors, including facilitating disclosure of HIV and other sexually transmitted infection (STIHIV) laboratory test results to sex partners. However, these studies, in which Black or African American sexual minority men were undersampled, failed to determine the relationship of reported history of discussing HIV results with sex partners and anticipated willingness to disclose web-based STIHIV test results using a patient portal. Among a sample of predominantly Black sexual minority men, this study aimed to (1) determine preferences for patient portal use for HIV prevention and (2) test the associations between reported history of discussing HIV results and anticipated willingness to disclose web-based STIHIV test results with most recent main and nonmain partners using patient portals. Data come from audio-computer self-assisted interview survey data collected during the 3-month visit of a longitudinal cohort study. Univariate analysis assessed patient portal preferences by measuring the valuation rankings of several portal features. Multiple Poisson regression models with robust error variance determined the associations between history of discussing HIV results and willingness to disclose those results using web-based portals by partner type, and to examine criterion validity of the enhancing dyadic communication (EDC) scale to anticipated willingness. Of the 245 participants, 71% (n174) were Black and 22% (n53) were White. Most participants indicated a willingness to share web-based STIHIV test results with their most recent main partner. Slightly fewer, nonetheless a majority, indicated a willingness to share web-based test results with their most recent nonmain partner. All but 2 patient portal features were valued as high or moderately high priority by >80% of participants. Specifically, tools to help manage HIV (n183, 75%) and information about pre- and postexposure prophylaxis (both 71%, n173 and n175, respectively) were the top-valuated features to include in patient portals for HIV prevention. Discussing HIV test results was significantly associated with increased prevalence of willingness to disclose web-based test results with main (adjusted prevalence ratio aPR 1.46, 95% CI 1.21-1.75) and nonmain partners (aPR 1.54, 95% CI 1.23-1.93). Our findings indicate what features Black sexual minority men envision may be included in the patient portals design to optimize HIV prevention, further supporting the criterion validity of the EDC scale. Efforts should be made to support Black sexual minority mens willingness to disclose STIHIV testing history and status with partners overall as it is associated significantly with a willingness to disclose testing results digitally via patient portals. Future studies should consider discussion behaviors regarding past HIV test results with partners when tailoring interventions that leverage patient portals in disclosure events.
36,826,980
HIV Epidemiology, Care, and Treatment Outcomes Among Student and Nonstudent Youths Living With HIV in Southwest China Between 1996 and 2019 Historical Cohort Study.
Nearly one-third of new HIV infections occurred among youth in 2019 worldwide. Previous studies suggested that student youths living with HIV and nonstudent youths living with HIV might differ in some risk factors, transmission routes, HIV care, and disease outcomes. This study aimed to compare the HIV epidemic, disease outcomes, and access to care among student and nonstudent youths living with HIV aged 16 to 25 years in Guangxi, China. We performed a historical cohort study by extracting data on all HIV or AIDS cases aged 16 to 25 years in Guangxi, China, during 1996-2019 from the Chinese Comprehensive Response Information Management System of HIV or AIDS. We conducted analyses to assess possible differences in demographic and behavioral characteristics, HIV care, and disease outcomes between student and nonstudent youths living with HIV. Multivariate Cox regression was used to assess differences in mortality and virologic failure between student and nonstudent cases. A total of 13,839 youths aged 16 to 25 years were infected with HIV during 1996-2019. Among them, 10,202 cases were infected through sexual contact, most of whom were men (n5507, 54%) 868 (8.5%) were students, and 9334 (91.5%) were not students. The number of student youths living with HIV was lower before 2006 but gradually increased from 2007 to 2019. In contrast, the nonstudent cases increased rapidly in 2005, then gradually declined after 2012. Student cases were mainly infected through homosexual contact (n614, 70.7% vs n1447, 15.5% P<.001), while nonstudent cases were more likely to be infected through heterosexual contact (n7887, 84.5% vs n254, 29.3% P<.001). Moreover, nonstudent cases had a significantly lower CD4 count than student cases at the time of HIV diagnosis (332 vs 362 cellsμL P<.001). Nonstudents also had a delayed antiretroviral therapy (ART) initiation compared to students (93 days vs 22 days P<.001). Furthermore, the mortality rate of 0.4 and 1.0 deaths per 100 person-years were recorded for student and nonstudent youths with HIV, respectively. Overall, the mortality risk in nonstudent cases was 2.3 times that of student cases (adjusted hazard ratio AHR 2.3, 95% CI 1.2-4.2 P.008). The virologic failure rate was 2.3 and 2.6 per 100 person-years among student and nonstudent youths living with HIV, respectively. Nonstudent cases had double the risk of virologic failure compared to student cases (AHR 1.9, 95% CI 1.3-2.6 P<.001). Nonstudent youths living with HIV might face a low CD4 count at the time of HIV diagnosis, delayed ART initiation, and increased risk of death and virologic failure. Thus, HIV prevention and interventions should target youths who dropped out of school early to encourage safe sex and HIV screening, remove barriers to HIV care, and promote early ART initiation to curb the HIV epidemic among youths.
36,826,779
Racial Differences in Social Determinants of Health and Outcomes Among HispanicLatino Persons with HIV-United States, 2015-2020.
HispanicLatino people with HIV (PWH) experience disparities in health outcomes compared with other racial and ethnic groups. Disaggregated data based on race for HispanicLatino PWH in the United States are rarely reported, potentially masking inequities. The Medical Monitoring Project (MMP) is a complex sample survey of adults with diagnosed HIV. We used weighted interview and medical record data collected from June 2015-May 2021 to examine differences in social determinants of health (SDH) and health outcomes by self-reported race among HispanicLatino adults with diagnosed HIV. Compared with White HispanicLatino PWH, Black HispanicLatino PWH were more likely to be unemployed (PR, 1.4 CI, 1.2-1.8), have a disability (PR, 1.3 CI, 1.2-1.5), have experienced homelessness (PR, 1.8 CI, 1.2-2.6), and have been incarcerated (PR, 2.6 CI, 1.5-4.5). American IndianAlaska Native (AIAN) (PR, 1.8 CI, 1.1-2.7) and multiracial (PR, 2.0 CI, 1.4-2.9) HispanicLatino PWH were more likely to have experienced homelessness than White HispanicLatino PWH. Black (PR, 1.3 CI, 1.2-1.5) and multiracial (PR, 1.2 CI, 1.1-1.5) HispanicLatino PWH were more likely to be virally unsuppressed than White HispanicLatino PWH. Black, multiracial, and AIAN HispanicLatino PWH experience disparities in SDH and HIV outcomes. Lumping HispanicLatino people into one racial and ethnic category obscures health disparities, which might limit our progress towards reaching national HIV goals. Future studies should consider disaggregating by other factors such as Hispanic origin, place of birth, immigration status, and primary language. Doing so recognizes the diversity of the HispanicLatino population.
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Safer Sex Negotiation Among Ghanaian Women in Sexual Unions Does Womens Household Decision-Making Capacity Matter
Womens ability to negotiate for safer sex has been found to be dependent on their household decision making power. However, there is paucity of studies investigating the association between womens household decision making power and safer sex negotiation in Ghana. Thus, we examined the association between womens household decision making autonomy and safer sex negotiation among Ghanaian women in sexual unions using the 2014 Ghanas Demographic and Health Survey. Descriptive statistics, Chi-square test, and multivariable logistic regression models were performed. Statistical significance was set at p < .05 at 95% confidence interval. The results showed high prevalence of safer sex negotiation among women with high household decision-making capacity (91.6%). Compared to women with low household decision making autonomy, those with high autonomy in household decision making were more likely to negotiate for safer sex (aOR 2.06 CI 1.32-3.21). Women aged 25-34 were more likely to negotiate for safer sex compared to those aged 15-24 (aOR 1.50 CI 1.07-2.11). Higher odds of safer sex negotiation were found among women with comprehensive HIV and AIDS knowledge (aOR 1.49 CI 1.09-2.05), women who had tested for HIV (aOR 1.57 CI 1.27-1.95) and those exposed to newspaper (aOR 1.80 CI 1.17-2.78) compared to those who had no comprehensive knowledge on HIV and AIDS, those who had never tested for HIV and those who were not exposed to newspaper, respectively. However, women who belonged to other ethnic groups and the Islamic religion had lower odds of safer sex negotiation compared to Akans (aOR 0.68 CI 0.48-0.96) and Christian women (aOR 0.63 CI 0.46-0.85). Women empowerment programmes need to be intensified to enable Ghanaian women with low household decision making autonomy to negotiate for safer sex with their partners. Ghana could achieve the Sustainable Development Goals (SDGs), particularly, SDG 3.7 (universal access to sexual and reproductive health services), and SDG 5 (achieve gender equality and empower all women and girls) when household decision-making capacity among women is further strengthened.
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HIV Infection Indicator Disease-Based Active Case Finding in a University Hospital Results from the SHOT Project.
In 2014, UNAIDS launched renewed global targets for HIV control to achieve by 2025, known as the three 95 95% of people living with HIV (PWH) diagnosed, of which 95% are receiving treatment, of which 95% are on sustained virological suppression. In Italy, new HIV diagnoses have been steadily decreasing since 2012. However, in 2020, 41% of new diagnoses presented with less than 200 CD4 cellsµL and 60% with less than 350 CD4 cellsµL. Implementing testing and early treatment is a key strategy to prevent AIDS, late presentation, and HIV transmission. We selected non-Infectious Diseases Units based on the European project HIDES and engaged colleagues in a condition-guided HIV screening strategy. We enrolled 300 patients, of which 202 were males (67.3%) and 98 were females (32.7%). Most of the screening was performed in Infectious Diseases (ID) and Hematologic wards. In total, we diagnosed eleven new HIV infections with a hospital prevalence in the study population of 3.7%. Five (45.4%) had a CD4 count <100mm
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Long-Term Survivors in a Cohort of People Living with HIV Diagnosed between 1985 and 1994 Predictive Factors Associated with More Than 25 Years of Survival.
Although the mortality rate among individuals diagnosed during the pre-Highly Active Antiretroviral Treatment era has been substantial, a considerable number of them survived. Our study aimed to evaluate the prevalence of HIV long-term survivors in a cohort of People Living with HIV diagnosed between 1985 and 1994 and to speculate about potential predictive factors associated to long survival. This is a retrospective single-center study. Subjects surviving more than 300 months (25 years) from HIV diagnosis were defined as Long Term Survivors. Overall, 210 subjects were enrolled. More than 75.24% of the included people living with HIV were males, with a median age of 28 years (IQR 25-34). The prevalent risk factors for HIV infection were injection drug use (47.62%), followed by unprotected sex among heterosexual individuals (23.81%). Ninety-three individuals (44.29%) could be defined as LTS with a median (IQR) survival of 333 (312-377) months. A hazard ratio of 12.45 (95% CI 7.91-19.59) was found between individuals who were exposed to Highly Active AntiRetroviral Treatment (HAART) and individuals who were not, with the latter being at greater risk of death. The availability and accessibility of effective antiretroviral therapy for people living with HIV remain the cornerstone of survival.
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Empowering Tennessee Pharmacists to Initiate PrEP Using Collaborative Pharmacy Practice Agreements.
The uptake of Pre-Exposure Prophylaxis (PrEP) has revolutionized the fight against the Human Immunodeficiency Virus (HIV) epidemic. Consistent obstacles remain that have influenced the slow uptake of PrEP in the United States of America (USA). In order to address these barriers, pharmacists must be included in the dispensing and management of PrEP through collaborative pharmacy practice agreements (CPPAs). Our aim for this study was to characterize pharmacists perceptions of initiating PrEP through a CPPA in the state of Tennessee. This qualitative study was conducted in the USA in 2021 with pharmacists practicing in Tennessee. A framework and specific questions guided the thematic analysis. The words and phrases were coded inductively and later collapsed into categories and placed into emergent themes. Two themes illustrate the voices of practicing pharmacists integration in the dispensing and management of PrEP (1) Learning from other states and previous successful CPPAs to advance and expand innovative models of patient care and (2) advocacy through public policy change to empower pharmacists to initiate PrEP. This qualitative study focused on exploring pharmacists perceptions on the opportunity of initiating PrEP through a CPPA in Tennessee. These findings highlight the preparedness of pharmacists to advocate for easier initiative of PrEP in pharmacies across Tennessee, whether through relaxing existing CPPA regulation or pursuing independent prescriptive authority for pharmacists.
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Pathogenesis, Diagnostic Challenges, and Risk Factors of Potts Disease.
Tuberculosis (TB) prevalence is increasing in developed nations and continuing to cause significant mortality in low- and middle-income countries. As a result of the uptick in cases, there also exists an increased prevalence of extrapulmonary TB. TB is caused by
36,826,057
Vaccine- and Breakthrough Infection-Elicited Pre-Omicron Immunity More Effectively Neutralizes Omicron BA.1, BA.2, BA.4 and BA.5 Than Pre-Omicron Infection Alone.
Since the emergence of SARS-CoV-2 Omicron BA.1 and BA.2, several Omicron sublineages have emerged, supplanting their predecessors. Here we compared the neutralization of Omicron sublineages BA.1, BA.2, BA.4 and BA.5 by human sera collected from individuals who were infected with the ancestral B.1 (D614G) strain, who were vaccinated (3 doses) or with breakthrough infection with pre-Omicron strains (Gamma or Delta). All Omicron sublineages exhibited extensive escape from all sera when compared to the ancestral B.1 strain and to Delta, albeit to different levels depending on the origin of the sera. Convalescent sera were unable to neutralize BA.1, and partly neutralized BA.2, BA.4 and BA.5. Vaccinee sera partly neutralized BA.2, but BA.1, BA.4 and BA.5 evaded neutralizing antibodies (NAb). Some breakthrough infections (BTI) sera were non-neutralizing. Neutralizing BTI sera had similar neutralizing ability against all Omicron sublineages. Despite similar levels of anti-Spike and anti-Receptor Binding Domain (RBD) antibodies in all groups, BTI sera had the highest cross-neutralizing ability against all Omicron sublineages and convalescent sera were the least neutralizing. Antibody avidity inferred from the NT50antibody titer ratio was highest in sera from BTI patients, underscoring qualitative differences in antibodies elicited by infection or vaccination. Together, these findings highlight the importance of vaccination to trigger highly cross-reactive antibodies that neutralize phylogenetically and antigenically distant strains, and suggest that immune imprinting by first generation vaccines may restrict, but not abolish, cross-neutralization.
36,825,949
Prevalence of Congenital Infections in Newborns and Universal Neonatal Hearing Screening in Santa Catarina, Brazil.
to verify the frequency of congenital infections in newborns and their possible associations with the universal-neonatal-hearing-screening (UNHS) results, and evaluate a reference UNHS service in the Unified Health System ( Historical cohort study with data analysis of newborns attending prestigious hearing-health SUS services from January 2017 to December 2021, in Santa Catarina, Brazil. The quality of screening coverage was assessed based on the quality indicators proposed by the Brazilian neonatal-hearing-screening-care guidelines ( In the last five years, the prestigious services performed UNHS on 34,801 newborns and met the DATAN quality indicators. Congenital syphilis was the most frequent (1.59%) congenital infection in newborns, followed by HIV (0.87%), whereas the least frequent was rubella (0.029%). Prestigious UNHS services reached ≥95% hearing screening coverage. Considering all congenital infections, the prevalence was 2.87%, with congenital syphilis the most frequent. Newborns with congenital syphilis or HIV are more likely to fail UNHS.
36,825,608
What are the risk factors for death among children with pneumonia in low- and middle-income countries A systematic review.
Knowledge of the risk factors for and causes of treatment failure and mortality in childhood pneumonia is important for prevention, diagnosis, and treatment at an individual and population level. This review aimed to identify the most important risk factors for mortality among children aged under ten years with pneumonia. We systematically searched MEDLINE, EMBASE, and PubMed for observational and interventional studies reporting risk factors for mortality in children (aged two months to nine years) in low- and middle-income countries (LMICs). We screened articles according to specified inclusion and exclusion criteria, assessed risk of bias using the EPHPP framework, and extracted data on demographic, clinical, and laboratory risk factors for death. We synthesized data descriptively and using Forest plots and did not attempt meta-analysis due to the heterogeneity in study design, definitions, and populations. We included 143 studies in this review. Hypoxaemia (low blood oxygen level), decreased conscious state, severe acute malnutrition, and the presence of an underlying chronic condition were the risk factors most strongly and consistently associated with increased mortality in children with pneumonia. Additional important clinical factors that were associated with mortality in the majority of studies included particular clinical signs (cyanosis, pallor, tachypnoea, chest indrawing, convulsions, diarrhoea), chronic comorbidities (anaemia, HIV infection, congenital heart disease, heart failure), as well as other non-severe forms of malnutrition. Important demographic factors associated with mortality in the majority of studies included age <12 months and inadequate immunisation. Important laboratory and investigation findings associated with mortality in the majority of studies included confirmed Pneumocystis jirovecii pneumonia (PJP), consolidation on chest x-ray, pleural effusion on chest x-ray, and leukopenia. Several other demographic, clinical and laboratory findings were associated with mortality less consistently or in a small numbers of studies. Risk assessment for children with pneumonia should include routine evaluation for hypoxaemia (pulse oximetry), decreased conscious state (e.g. AVPU), malnutrition (severe, moderate, and stunting), and the presence of an underlying chronic condition as these are strongly and consistently associated with increased mortality. Other potentially useful risk factors include the presence of pallor or anaemia, chest indrawing, young age (<12 months), inadequate immunisation, and leukopenia.
36,825,555
Longitudinal impact of stressful life events on HIV-related risk and psychosocial problems among MSM in Chennai and Mumbai, India.
Studies show that stressful life events (SLE) (e.g., discrimination, financial problems) can lead to psychosocial problems and exacerbate condomless anal sex (CAS) without protection via pre-exposure prophylaxis (PrEP) among men who have sex with men. However, few studies have examined this relationship among men who have sex with men in India, and none have examined this longitudinally. As a part of an HIV-prevention intervention, 608 MSM from Chennai and Mumbai, India, completed behavioral surveys at baseline, 4, 8, and 12 months. We used longitudinal generalized estimating equations (GEE) modeling to examine the relationship between SLE and its severity and subsequent psychosocial problems, CAS, and history of diagnosed sexually transmitted infection (STI). All models are adjusted for age, sexual identity, intervention arm, human immunodeficiency virus status, and recruitment city. The number of SLE and their corresponding perceived impact score remained consistent at each time point. In multivariable GEE models, the number of SLE was predictive of CAS, depression, and harmful drinking. Similarly, the ratio of the impact of SLE was predictive of CAS, depression, and diagnosed STI. However, harmful drinking was not predictive in this model. These findings provide evidence that can inform future interventions, which can be used to enhance self-acceptance, coping skills, and other forms of resiliency.
36,825,536
HSV-2 prevalence and association with inflammatory cytokines among sexual and gender minorities (SGM) living with and without HIV-1 from Lagos, Nigeria.
Herpes simplex virus type 2 (HSV-2) is common globally and contributes significantly to the risk of acquiring HIV-1, yet these two sexually transmitted infections (STIs) have not been sufficiently characterized for sexual and gender minorities (SGM) across sub-Saharan Africa. To help fill this gap, we performed a retrospective study using plasma and serum samples from 183 SGM enrolled at the Lagos site of the TRUSTRV368 cohort in Nigeria, assayed them for HSV-2 antibodies with the Kalon ELISA and plasma cytokines and chemokines with Luminex, and correlated the findings with HIV-1 viral loads and CD4 counts. We found an overall HSV-2 prevalence of 36.6% (49.5% and 23.9% among SGM with and without HIV-1, respectively, p<0.001). Moreover, HSV-2 positive status was associated with high circulating concentrations of CCL11 among antiretroviral therapy (ART) treated (p0.031) and untreated (p0.015) participants, and with high concentrations of CCL2 in the untreated group (p0.004), independent of VL. Principal component analysis revealed a strong association of cytokines with HIV-1 viral load independent of HSV-2 status. In conclusion, our study finds that HSV-2 prevalence among SGM with HIV-1 is twice as high than HSV-2 prevalence among SGM without HIV-1 in Lagos and suggests that this is associated with higher levels of certain systemic cytokines. Additional work is needed to further characterize the relationship between HSV-2 and HIV-1 in SGM and help develop targeted therapies for co-infected individuals.
36,825,522
Immune cell cross talk in the establishment of HIV-1 latency.
Revolutionary progress in combinational antiretroviral therapy (cART) has transformed Human Immunodeficiency Virus (HIV) infection into a chronic manageable disease yet there exists an uneasy truce between the virus and the immune cells, where inflammation is limited but infection continues to fester from latent reservoirs of the virus. Clinical studies have identified the major immune cell types that constitute the latent HIV-1 reservoirs as monocytesmacrophages and CD4 T cells. Latency probing approaches have thrown some light on the interaction between the virus and the reservoir cells from the time of onset of infection. However, research combining latency reversal strategies and immunotherapies face daunting obstacles in clinical trials because of the lack of in-depth knowledge on viral pathogenesis and mechanisms of viral evasion, leaving us behind in the battle for HIV cure. This article reviews existing knowledge on the cells and mechanisms that contribute to the establishment and survival of HIV reservoirs in infected individuals.
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The influence of HIV and its treatment on Hypertensive Disorders Of Pregnancy (HDP) in women from a low to middle income country.
To establish a potential relationship between HDP and HIV infection METHODS This cross sectional observational study involving 300 women with HDP was undertaken from September 2018 to February 2019, in a regional hospital in Durban, South Africa, a setting with a background HIV prevalence of 45% among pregnant women. All women with new onset elevation of blood pressure after the 20 0f the 300 women with HDP, the HIV prevalence was 30%, compared to the historical seroprevalence of 45% within the hospital, p0.028. For all categories of HDP, there were fewer primigravid women amongst women living with HIV (WLHIV), compared to those uninfected 30% versus 50.2% respectively, p0.001 HDP developed later in gestation in WLHIV compared to uninfected women, (32.6 versus 34 weeks respectively, (p0.023), however, there were significant maternal complications of abruption and elevated liver enzymes amongst WLHIV, (p0.02 and 0.014 RESPECTIVELY). CONCLUSION HIV or its treatment seems to have a protective effect in the development of HDP, however, the complications of HDP may be significant in WLHIV receiving treatment.
36,825,492
Isothermal nucleic acid amplification technology in HIV detection.
Nucleic acid testing for HIV plays an important role in the early diagnosis and monitoring of antiretroviral therapy outcomes in HIV patients and HIV-infected infants. Currently, the main molecular diagnostic methods employed are complex, time-consuming, and expensive to operate in resource-limited areas. Isothermal nucleic acid amplification technology overcomes some of the shortcomings of traditional assays and makes it possible to use point-of-care tests for molecular HIV detection. Here, we summarize and discuss the latest technological advances in isothermal nucleic acid amplification for HIV detection, with the intent of providing guidance for the development of subsequent HIV assays with high sensitivity and specificity.
36,825,369
System mapping with adolescents Using group model building to map the complexity of obesity.
Public health research and practice is increasingly employing systems thinking to help grapple with complex issues, from obesity to HIV treatment. At the same time, there is growing recognition that to address a given problem it is essential collaborate with those most at risk of or affected by it. Group model building (GMB), a process grounded in system dynamics, combines systems thinking and participatory methods to structure and address complex issues. As part of the CO-CREATE project we conducted GMB sessions with young people in six countries to create causal loop diagrams showing the factors that they believe drive obesity. This paper describes the background to GMB and the process we used to construct causal loop diagrams it discusses how GMB contributed to generating noteworthy and useful findings, and the strengths and limitations of the method. Using GMB, we identified areas of concern to adolescents in relation to obesity that have so far had little attention in obesity research and policy mental health and online activity. In using GMB, we also helped answer calls for a more participatory approach to youth involvement in research and policy development.
36,825,290
Study on molecular mechanisms of CD4 dependency and independency of HIV-1 gp120.
Different HIV-1 strains have different antibody neutralization phenotypes (or CD4-dependencies). However, the molecular mechanisms underlying these differences remain to be elucidated. In this study, we constructed gp120 structural models from the CD4-dependent, neutralization-resistant JR-FL strain and the CD4-independent, neutralization-sensitive R2 strain and carried out several conventional molecular dynamics (MD) simulations and free energy landscape (FEL) constructions. Comparative analyses of the MD simulations and FELs indicated that R2 gp120 had higher global structural flexibility and greater conformational diversity than JR-FL gp120. This provides the preconditions for R2 gp120 to adopt a more open conformation than JR-FL gp120. Essential dynamics (ED) analysis showed that the collective motions of R2 gp120 tend towards an open state while those of JR-FL gp120 tend to retain a closed state. Based on conformational selection theory, R2 gp120s more readily sampled open state makes it more sensitive to neutralizing antibodies (or more CD4-independent) than JR-FL gp120, which may explain why the HIV-1 R2 and JR-FL strains show CD4-independent and -dependent phenotypes, respectively. Our study provides thermodynamic and kinetic insights into the CD4-dependent and -independent molecular mechanisms of HIV-1 gp120 and helps shed light on HIV-1 immune evasion.
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Cochrane corner community-level interventions to increase access to food in low- and middle-income countries.
Food insecurity and hunger is a continuing problem in Africa, with access to food being critical to address it. Community-level interventions may help to increase access to food, specifically, nutritious food. We highlight a Cochrane review that assessed community level interventions aiming to increase access to nutritious food in low- and middle-income countries (LMICs), including those that improve buying power, address food prices, and the social environment. Randomised controlled trials and prospective controlled studies that assessed the effects of these interventions on food security and nutritional status were included, providing relevant implications for practice in LMICs. Findings suggest that unconditional cash transfers (UCTs) are important for improving food security, and that UCTs and food vouchers may increase dietary diversity and reduce stunting. This highlights the importance of current programmes in Africa, the need to reflect and refine where needed, and expand their capacity. A holistic approach to address food insecurity in the region.
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Evaluation of the HIV drug resistance surveillance system in Mozambique, 2017-2018.
In the past ten years, the prevalence of primary Human Immunodeficiency Virus (HIV) drug resistance has ranged from zero to 25%, with higher and increasing rates in countries with access to antiretroviral therapy (ART), a specific case in Mozambique. World Health Organization (WHO) recommended that countries implement and routinely evaluate representative HIV drug resistance (HIVDR) research to monitor the emergency and transmission of HIV drug resistance mutations. This study aimed to describe the functioning of the system and also to identify gaps in the sensitivity, representativeness and quality of the data using the WHO methodology for Pre-Treatment and Acquired Approaches. We conducted a descriptive evaluation of the information system for surveillance of HIVDR in Mozambique in 2017-2018, based on updated guidelines for evaluating of public health surveillance systems from the Center for Disease Control and Prevention (CDC). The evaluation was conducted in all provinces using secondary data extracted from a cross-sectional survey database on HIVDR, with HIV positive cases at the beginning of ART aged ≥15 years. The system was described through informal conversations with HIVDR stakeholders and the simplicity, data quality and representativeness attributes were evaluated. With 322 positive cases at the beginning of ART (mean age32.5 years, SD±11.1), about 63.0% (203322) cases were women and 37.6% (121322) men. The system was implemented in 25 health facilities distributed across all 11 Mozambican provinces and was considered representative. The system used two data collection instruments, the ART book and the form accompanying samples sent to the reference laboratory. The ART form, with 27 variables, was sent offline at two levels (health facility and National Institute of Health (NHI)), accompanied by dried blood spot samples for viral load testing and genotyping in the NHI virology laboratory, and was considered simple according to the standardized criteria. The system´s data quality was considered regular at 79.9%, with about 59.8% (11561932) of variable fields completed and 100% (19321932) consistency. The system used a single national laboratory to measure the prevalence of resistance to HIV drugs and was considered simple, with regular quality and representative data. We recommended public health efforts such as conducting genotyping tests be expanded to the provincial level, and periodic monitoring of system´s data collection procedures using forms.
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Presynaptic Hemiparkinsonism Following Cerebral Toxoplasmosis Case Report and Literature Review.
Cerebral toxoplasmosis (CTx) is a central nervous system opportunistic infection with variable neurological manifestations. Although tropism of We report a human immunodeficiency virus-positive patient who developed a complex MD featuring unilateral tremor combined with parkinsonism and dystonia following an acute episode of disseminated CTx. Her dopamine transporter scan (DaTscan) documented contralateral presynaptic dopaminergic deficit. Levodopa initiation improved both tremor and parkinsonism after ineffective trials of several other medications over the years. A total of 64 patients presenting with CTx-related MDs have been described. The most common MD was chorea (44%), followed by ataxia (20%), parkinsonism (16%), tremor (14%), dystonia (14%), myoclonus (3%), and akathisia (2%). DaTscan was performed only in 1 case, of Holmes tremor, that demonstrated reduced presynaptic dopaminergic uptake. Positive response to dopaminergic treatment was reported in 3 cases of Holmes tremor and 2 cases of parkinsonism. Presynaptic dopaminergic deficit may occur in CTx-related tremor combined with parkinsonism. Its identification should prompt initiation of levodopa, thus avoiding unnecessary trials of other drugs.
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Assessment of anti-CD20 antibody pre-treatment for augmentation of CAR-T cell therapy in SIV-infected rhesus macaques.
During chronic HIV and SIV infections, the majority of viral replication occurs within lymphoid follicles. In a pilot study, infusion of SIV-specific CD4-MBL-CAR-T cells expressing the follicular homing receptor, CXCR5, led to follicular localization of the cells and a reduction in SIV viral loads in rhesus macaques. However, the CAR-T cells failed to persist. We hypothesized that temporary disruption of follicles would create space for CAR-T cell engraftment and lead to increased abundance and persistence of CAR-T cells. In this study we treated SIV-infected rhesus macaques with CAR-T cells and preconditioned one set with anti-CD20 antibody to disrupt the follicles. We evaluated CAR-T cell abundance and persistence in four groups of SIVmac239-infected and ART-suppressed animals untreated, CAR-T cell treated, CD20 depleted, and CD20 depletedCAR-T cell treated. In the depletion study, anti-CD20 was infused one week prior to CAR-T infusion and cessation of ART. Anti-CD20 antibody treatment led to temporary depletion of CD20 cells in blood and partial depletion in lymph nodes. In this dose escalation study, there was no impact of CAR-T cell infusion on SIV viral load. However, in both the depleted and non-depleted animals, CAR-T cells accumulated in and around lymphoid follicles and were Ki67. CAR-T cells increased in number in follicles from 2 to 6 days post-treatment, with a median 15.2-fold increase in follicular CAR-T cell numbers in depletedCAR-T treated animals compared to an 8.1-fold increase in non-depleted CAR-T treated animals. The increase in CAR T cells in depleted animals was associated with a prolonged elevation of serum IL-6 levels and a rapid loss of detectable CAR-T cells. Taken together, these data suggest that CAR-T cells likely expanded to a greater extent in depletedCAR-T cell treated animals. Further studies are needed to elucidate mechanisms mediating the rapid loss of CAR-T cells and to evaluate strategies to improve engraftment and persistence of HIV-specific CAR-T cells. The potential for an inflammatory cytokine response appears to be enhanced with anti-CD20 antibody treatment and future studies may require CRS control strategies. These studies provide important insights into cellular immunotherapy and suggest future studies for improved outcomes.
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Extracellular vesicle-Serpine-1 affects neural progenitor cell mitochondrial functions and synaptic density modulation by amyloid beta and HIV-1.
Brain endothelial extracellular vesicles carrying amyloid beta (EV-Aβ) can be transferred to neural progenitor cells (NPCs) leading to NPC dysfunction. However, the events involved in this EV-mediated Aβ pathology are unclear. EV-proteomics studies identified Serpine-1 (plasminogen activator inhibitor 1, PAI-1) as a major connecting hub on several protein-protein interaction maps. Serpine-1 was described as a key player in Aβ pathology and was linked to HIV-1 infection as well. Therefore, the aim of this work was to address the hypothesis that Serpine-1 can be transferred via EVs from brain endothelial cells to NPCs and contribute to NPC dysfunction. HBMEC concentrated and released Serpine-1 via EVs, the effect that was potentiated by HIV-1 and Aβ. EVs loaded with Serpine-1 were readily taken up by NPCs, and HIV-1 enhanced this event. Interestingly, a highly specific Serpine-1 inhibitor PAI039 increased EV-Aβ transfer to NPCs in the presence of HIV-1. PAI039 also partially blocked mitochondrial network morphology and mitochondrial function alterations in the recipient NPCs, which developed mainly after HIV Aβ-EV transfer. PAI039 partly attenuated HIV-EV-mediated decreased synaptic protein levels in NPCs, while increased synaptic protein levels in NPC projections. These findings contribute to a better understanding of the complex mechanisms underlying EV-Serpine-1 related Aβ pathology in the context of HIV infection. They are relevant to HIV-1 associated neurocognitive disorders (HAND) in an effort to elucidate the mechanisms of neuropathology in HIV infection.
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The association between childhood adversity and the conserved transcriptional response to adversity (CTRA) in sexual minority men.
Adverse childhood experiences (ACES) increase risk for mental and physical health disorders in adulthood, particularly in individuals from sexual and ethnic minority groups. The effects of ACES on health may be mediated by the immune system. The exact mechanisms by which an environmental exposure, such as childhood adversity, can affect the immune system are still unknown. The aim of this study was to determine whether early adversity predicts significant changes in the expression of a predefined set of immune-related genes, known as the conserved transcriptional response to adversity (CTRA), in a diverse group of sexual minority men (SMM). Participants included HIV positive and negative males from the mSTUDY. Expression data from 53 CTRA genes were obtained at baseline and 12-month follow-up. Childhood adversity was measured with the 10-item ACES questionnaire. Wilcoxon rank sum and chi-squared tests were used to assess differences in sociodemographic variables and HIV status between exposed (cumulative ACES ≥ 3) and unexposed groups (cumulative ACES ≤ 2). Linear mixed models were used to determine associations between ACES (cumulative score, dichotomous measure and subscales) and CTRA gene expression. There were no differences in age and employment status between the exposed and unexposed groups. A larger number of exposed participants were HIV positive than in the unexposed group (p 0.03). There were no significant associations between any of the ACES variables and CTRA gene expression. A range of factors may have contributed to this unexpected finding. Further studies are needed to assess the biological effects of ACES in adulthood.
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Measuring Stigma Associated with Hepatitis B Virus Infection in Sierra Leone Validation of an Abridged Berger HIV Stigma Scale.
Stigma associated with hepatitis B virus (HBV) is common in endemic countries however instruments are lacking to accurately measure HBV-related stigma. We therefore aimed to develop and validate a concise instrument for measuring perceived HBV-related stigma in Sierra Leone. We enrolled 220 people living with HBV (PWHB) aged ≥ 18 years from August to November 2022. The initial Likert-scale instrument entailed 12 items adapted from Bergers HIV Stigma Scale. We included 4 additional items adapted from the USAID indicators for enacted stigma. The proposed scales psychometric properties were assessed. After item reduction, the final HBV Stigma Scale consisted of 10 items and had good internal consistency (overall Cronbachs α 0.74), discriminant and construct validity. Exploratory factor analysis produced a 3-dimensional structure accounting for 59.3% of variance personalized stigma driven by public attitudes (6 items), negative self-image (2 items), and disclosure concerns (2 items). Overall, 72.8% of respondents reported perceived HBV stigma (mean score 29.11 ± 4.14) and a similar a proportion (73.6%) reported at least one instance of enacted stigma. In assessing criterion-related validity, perceived HBV-related stigma correlated strongly with enacted stigma (r 0.556) and inversely with having familyfriends with HBV (r -0.059). The 10-item HBV Stigma Scale demonstrated good internal consistency and validity and is suitable for screening for HBV-related stigma in Sierra Leone. The psychometric properties of the scale can be optimized with item additionsmodifications and confirmatory factor analysis. The scale may help in combating stigma as a barrier to achieving HBV global elimination goals.
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HIV-1 interaction with an O-glycan-specific bacterial lectin enhances virus infectivity and cell-to-cell viral transfer.
While bacterial dysbiosis has been associated with increased HIV-1 transmission risk, little is known about direct associations between HIV-1 and bacteria. This study evaluated HIV-1 interactions with bacteria through glycan-binding lectins that affect virus infectivity. The Streptococcal Siglec-like lectin SLBR-N, which is part of the fimbriae shrouding the bacteria surface and recognizes α2,3 sialyated O-linked glycans, was noted for the ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. SLBR-N was demonstrated to capture HIV-1 virions, bind to O-glycans on HIV-1 Env, and augment CD4 binding to Env. Other SLBRs recognizing distinct O-glycans also enhanced HIV-1 infectivity, albeit to lower extents, whereas N-glycan-binding bacterial lectins FimH and Msl had no effect. Enhancing effects were recapitulated with O-glycan-binding plant lectins. Hence, this study highlights the potential contribution of O-glycans in promoting HIV-1 infection through the exploitation of O-glycan-binding lectins from commensal bacteria at the mucosa.
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Ionic Liquid Coating-Driven Nanoparticle Delivery to the Brain Applications for NeuroHIV.
Delivering cargo to the central nervous system (CNS) remains a pharmacological challenge. For infectious diseases such as HIV, the CNS acts as a latent reservoir that is inadequately managed by systemic antiretrovirals (ARTs). ARTs thus cannot eradicate HIV, and given CNS infection, patients experience an array of neurological deficits that are collectively referred to as neuroHIV. Herein we report the development of bioinspired ionic liquid-coated nanoparticles (IL-NPs) for
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The impact of carceral churn and healthcare organizations on HIVAIDS incidence in Arkansas.
•Penal and healthcare institutions generate and mitigate community-level health inequality, respectively.•Arkansas Counties with high prison churn and disadvantage have higher rates of HIVAIDS.•Hospital density moderates effect of prison churn on incidence of HIVAIDS.
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Acute HIV Presenting With Unilateral Facial Nerve Paralysis A Case Report.
Cranial nerve VII palsy is one of the most common cranial nerve pathologies seen in clinical practice. In the vast majority of cases, the cause is thought to be idiopathic and is also referred to as Bells palsy. These cases are normally self-limiting and often treated with a short course of corticosteroids for symptom management. However, prompt work-up and diagnosis are crucial, as non-idiopathic causes can often be life-altering and necessitate prompt intervention. Here, we report a unique case of a 43-year-old immigrant male who presented to the emergency department with a three-day history of worsening facial droop and slurred speech, with associated facial pain, headaches, and dizziness for the previous week. On exam, there was stark right facial weakness involving both the upper and lower portions of the face with no sensory deficits. The patients right eye was erythematous and painful, with no ability to fully open or close the right eyelid. The initial workup showed minor transaminitis with pancytopenia. A thorough workup was initiated, and all testing and serology were normal, with the exception of initial HIV screening. This was then followed by polymerase chain reaction (PCR) and viral load testing, which confirmed a new diagnosis of acute HIV infection presenting with unilateral CN VII palsy. In this report, we discuss the etiology, clinical features, differentials, and treatment options for facial nerve paralysis, along with the subtle connection to acute HIV infection.
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Hormone Prescription and HIV ScreeningPreventive Practices Among Clinicians Providing Care for Transgender Individuals.
Through a survey-based approach, we sought to investigate regional differences in gender-affirming hormone therapy (GAHT) prescribing practices, as well as HIV screening and prevention practices among clinicians providing care to transgender individuals. Our survey was disseminated between December 2019 and January 2021 to clinicians who prescribe GAHT within New England (United States). Between-group differences in GAHT prescribing and HIV screeningprevention practices were evaluated by practice setting and subspecialty. Of the 20 survey respondents, 55% practiced in health care settings affiliated with an academic institution, 45% practiced in a community-based health care setting, and 30% were Endocrinologists. Clinicians in community-based health care settings reported more frequently prescribing oral 17β-estradiol ( Regional GAHT prescribing practices varied by setting. Additional research is needed to better understand whether these differences translate to differences in GAHT efficacy and side-effects. Further, HIV screeningprevention practices varied by subspecialty. Integrated GAHT and HIV screeningprevention across subspecialties could help reduce the disproportionate burden of HIV faced by the transgender community.
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The Pattern of Tuberculosis in Iran A National Cross-Sectional Study.
Despite of the remarkable achievement in control of tuberculosis, it is still a challenging health problem in Iran. Success in any health program depends on monitor the diseases epidemiology and finding the gaps. We aimed to describe the epidemiological profile of TB patients in Iran to find the gaps in the TB program and using the finding to set the program activities. This cross-sectional study was performed based on the data of tuberculosis patients registered in Iran in 2016-2017. The information of all TB patients is registered in the TB registry software. The patients were followed during the treatment phase. The data were analyzed by SPSS 23 software using Chi-Square test. Overall 12% of cases were Afghans and 72.3% of patients had pulmonary tuberculosis. There was a significant difference in the success rate of treatment in smear-positive pulmonary patients by gender, HIV status, marital status, history of hospitalization and incarceration ( Despite of the TB treatment success and low prevalence of MDR cases, TB incidence has not been decreased significantly in Iran. Delay in diagnosis, high TB burden in refugees and close contact investigation and prophylaxis are important issues in the TB control program in Iran to be considered in the control planning.
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Superwoman schema uncovering repercussions of coping strategies used among Black women at high risk for HIV.
The Superwomen Schema (SWS) describes a social framework that encompasses the role that many Black women adopt in response to chronic stress, financial pressures, and an intersection of oppression. Woods-Giscombé (Superwoman Schema African American Womens Views on Stress, Strength, and Health. Qualitative Health Research 20 (5) 668-683, 2010) characterizes SWS using five tenets obligation to manifest strength, obligation to suppress emotions, resistance to vulnerability or dependency, determination to succeed despite a lack of resources, and an obligation to help others. The goal of this study is to determine the connection between SWS among Black women and substance use as a means of maintaining mental health, garnering resilience, and coping with external pressures. We aimed to highlight systemic and infrastructural racism and prejudice and how they relate, not only to the adoption of SWS, but also how they may contribute to substance use. This study is a secondary analysis of a larger study on HIV prevention Black and Latine women at high risk for HIV. Only Black participants (n 10) were included in this secondary analysis. The interviews were conducted 3 times across 3 months. Interviews were coded and analyzed using thematic content analysis in NVivo. Themes of undiagnosed mental health symptoms, medical mistrust, institutional distrust, and aversion to help-seeking were recurrent in our data. Our research confirmed and assessed dual repercussions of SWS among Black women both as a defense that granted resilience in the face of seemingly insurmountable odds and as a construct that encouraged substance use as a coping mechanism for compromised mental health. This study contextualized this subset of coping and substance use to address and dismantle systemic contributors.
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Cultural Repertoires and Situated Selections as an Alternative Framework to Hegemonic Masculinities Findings From Eswatini.
Since the 1980s studies on men have frequently utilized Connells framework of hegemonic masculinities. We critically appraise this framework in the context of a population-based HIV pre-exposure prophylaxis study in Eswatini. Our findings highlight that men confidently show variation in their behavior and choices, which manifest across different men and within the same men acting in particular situations and over the life course. This led us to interrogate the hegemonic masculinities framework on the following grounds Mens choices and behavior do not seem to fit the model of aspiring to a hegemonic ideal the delineation of masculine traits as hegemonic or subordinate remain vague in terms of responsibility, fidelity, and consideration for others the binary gender concept underpinning hegemonic masculinities seems outdated. Building on the work of Hirsch and Kachtan, we propose cultural repertoires as an alternative framework which also bridges the gender divide.
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Emergomyces pasteurianus in Man Returning to the United States from Liberia and Review of the Literature.
A 65-year-old man with HIV sought treatment for fever, weight loss, and productive cough after returning to the United States from Liberia. Fungal cultures grew Emergomyces pasteurianus, and the patients health improved after beginning voriconazole. We describe the clinical case and review the literature, treatment, and susceptibilities for E. pasteurianus.
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Incidence and risk factors of hypertriglyceridemia in males with human immunodeficiency virus who are treated with combination antiretroviral therapy a retrospective cohort study.
Hypertriglyceridemia is associated with subclinical atherosclerosis and vascular inflammation even when low-density lipoprotein cholesterol levels are normal. However, few cohort studies on hypertriglyceridemia have been conducted in males with higher susceptibility to human immunodeficiency virus (HIV)-related deterioration of arterial structure and function. Our objective was to investigate the incidence of hypertriglyceridemia during treatment with combination antiretroviral therapy (cART) in males with HIV and explore its related risk factors. In this retrospective study, we included 309 males living with HIV (median age 31 years interquartile range 26-42.5) who initiated cART treatment in our hospital from January 2013 to December 2018. We collected follow-up data on serum triglycerides and other related information as of June 31, 2021. A Cox proportional hazards regression model was used to analyze the related risk factors. In 666.7 person-years, hypertriglyceridemia occurred in 140 patients (triglyceride ≥2.3 mmolL 200 mgdL), and the incidence rate was 21.0 per 100 person-years (Patients who took the lamivudine 3TC tenofovir disoproxil fumarate TDF efavirenz EFV regimen accounted for 77.0% of the total patients.). Multiple Cox regression analysis showed that baseline CD4CD8 ratio < 0.20 (hazard ratio HR, 2.705 95% confidence interval (CI) 1.381-5.296 P 0.004, body mass index (BMI) ≥ 24.0 kgm During the course of cART treatment, the incidence of hypertriglyceridemia in males with HIV was high. The main risk factors influencing its occurrence are a low baseline CD4CD8 ratio, overweight and obesity, and the use of AZT or LPVr in the cART regimen.
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Public health determinants of child malaria mortality a surveillance study within Siaya County, Western Kenya.
Malaria deaths among children have been declining worldwide during the last two decades. Despite preventive, epidemiologic and therapy-development work, mortality rate decline has stagnated in western Kenya resulting in persistently high child malaria morbidity and mortality. The aim of this study was to identify public health determinants influencing the high burden of malaria deaths among children in this region. A total of 221,929 children, 111,488 females and 110,441 males, under the age of 5 years were enrolled in the Kenya Medical Research InstituteCenter for Disease Control Health and Demographic Surveillance System (KEMRICDC HDSS) study area in Siaya County during the period 2003-2013. Cause of death was determined by use of verbal autopsy. Age-specific mortality rates were computed, and cox proportional hazard regression was used to model time to malaria death controlling for the socio-demographic factors. A variety of demographic, social and epidemiologic factors were examined. In total 8,696 (3.9%) children died during the study period. Malaria was the most prevalent cause of death and constituted 33.2% of all causes of death, followed by acute respiratory infections (26.7%) and HIVAIDS related deaths (18.6%). There was a marked decrease in overall mortality rate from 2003 to 2013, except for a spike in the rates in 2008. The hazard of death differed between age groups with the youngest having the highest hazard of death HR 6.07 (95% CI 5.10-7.22). Overall, the risk attenuated with age and mortality risks were limited beyond 4 years of age. Longer distance to healthcare HR of 1.44 (95% CI 1.29-1.60), l ow maternal education HR 3.91 (95% CI 1.86-8.22), and low socioeconomic status HR 1.44 (95% CI 1.26-1.64) were all significantly associated with increased hazard of malaria death among children. While child mortality due to malaria in the study area in Western Kenya, has been decreasing, a final step toward significant risk reduction is yet to be accomplished. This study highlights residual proximal determinants of risk which can further inform preventive actions.
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SARS-CoV-2 antibody prevalence, correlates, and access to harm reduction services among people who inject drugs living with and without HIV and their partners in Kenya.
In sub-Saharan Africa many people who inject drugs (PWID) are living with undiagnosed or untreated HIV and experience high levels of poverty and conditions that can contribute to worse outcomes from SARS-CoV-2 infection. Identifying the burden of SARS-CoV-2 infection in marginalized populations like PWID may contribute to controlling the pandemic. This is a nested cross-sectional study within an ongoing cohort study that recruits PWID living with HIV and their injecting andor sexual partners at needle and syringe program sites and methadone clinics in Kenya. Blood samples were collected from consenting participants at enrollment to determine SARS-CoV-2 antibodies using a Platellia BioRad SARS-CoV-2 total antibody enzyme-linked immunosorbent assay. Baseline data were collected on HIV status, antiretroviral therapy and methadone adherence. We used logistic regression to identify factors associated with antibody positivity and descriptive statistics to report SARS-CoV-2 antibody prevalence. One thousand participants were enrolled between April and July 2021, of whom 323 (32.3%) were women and 677 (67.7%) were men. Median age of participants was 36 years (interquartile range 30, 42). SARS-CoV-2 antibody positivity was found in 309 (30.9%) participants. Disruption in obtaining methadone service was reported by 106 (24.3%) of the participants. Men were significantly less likely than women to have SARS-CoV-2 antibodies (adjusted odds ratio aOR 0.68, 95% confidence interval CI 0.51, 0.95 p < 0.01) Participants who reported a sexual or injecting partner diagnosed with SARS-CoV-2 were twofold more likely to have SARS-CoV-2 antibodies detected (aOR 2.21, 95% CI 1.06, 4.58 p < 0.032). Living with HIV was not associated with presence of SARS-CoV-2 antibodies. The seroprevalence of SARS-CoV-2 of 30.9% in this cohort suggests high transmission rates within this population. SARS-CoV-2 seroprevalence was similar for people living with and without HIV. A large portion of this population was noted to have had disruption in access to harm reduction services.
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Applying mathematical modelling to estimate the impact of COVID-19-related VMMC service disruptions on new HIV infections in Zimbabwe.
The COVID-19 pandemic has overwhelmed health systems with knock on effects on diagnosis, treatment, and care. To mitigate the impact, the government of Zimbabwe enforced a strict lockdown beginning 30 March 2020 which ran intermittently until early 2021. In this period, the Ministry of Health and Childcare strategically prioritized delivery of services leading to partial and full suspension of services considered non-essential, including HIV prevention. As a result, Voluntary Medical Male Circumcision (VMMC) services were disrupted leading to an 80% decline in circumcisions conducted in 2020. Given the efficacy of VMMC, we quantified the potential effects of VMMC service disruption on new HIV infections in Zimbabwe. We applied the GOALS model to evaluate the impact of COVID-19-related disruptions on reducing new HIV infections over 30-years. GOALS is an HIV simulation model that estimates number of new HIV infections based on sexual behaviours of population groups. The model is parameterized based on national surveys and HIV program data. We hypothesized three coverage scenarios by 2030 scenario I - pre-COVID trajectory 80% VMMC coverage Scenario II - marginal COVID-19 impact 60% VMMC coverage, and scenario III - severe COVID-19 impact 45% VMMC coverage. VMMC coverage between 2020 and 2030 was linearly interpolated to attain the estimated coverage and then held constant from 2030 to 2050, and discounted outcomes at 3%. Compared to the baseline scenario I, in scenario II, we estimated that the disruption of VMMC services would generate an average of 200 (176-224) additional new infections per year and 7,200 new HIV infections over the next 30 years. For scenario III, we estimated an average of 413 (389-437) additional new HIV infections per year and 15,000 new HIV infections over the next 30 years. The disruption of VMMC services could generate additional future HIV treatment costs ranging from $27 million to $55 million dollars across scenarios II and III, respectively. COVID-19 disruptions destabilized delivery of VMMC services which could contribute to an additional 7,200 new infections over the next 30 years. Unless mitigated, these disruptions could derail the national goals of reducing new infections by 2030.
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Nurses reflections on caring for sexual and gender minorities pre-post stigma reduction training in Uganda.
Men who have sex with men (MSM) and transgender women (TGW) have a significant HIV burden worldwide. Data from eight countries across sub-Saharan Africa found a pooled HIV prevalence of 14% among MSM and 25% among TGW. Stigma and discrimination among healthcare providers are barriers to healthcare access by these populations. We sought to explore nurses attitudes before and after sensitivity training to reduce stigma in HIV prevention and care provision to MSM and transgender persons in Uganda. An explorative qualitative study comprising in-depth interviews. Nineteen nurses who underwent sensitivity training in caring for the vulnerable, priority and key populations in Uganda participated. We interviewed each participant before and after the stigma reduction training and analyzed the data with NVivo. Eight (8) themes emerged from the reflections before the training, namely, the definition of MSM and transgender persons, legal concerns, mental illness, attitude in health care provision, personal perceptions, self-efficacy, insufficient training preparation, and reasons for gender or sexual orientation preference. The post-training reflections suggested a change in knowledge and attitude. Five themes emerged for MSM stigma reduction, sexual practices and sexuality, the need for tailored health approaches, MSM and the law and corrected misconceptions. For transmen, reproductive health needs, social needs, safety needs, Gender identity recognition and reduced stigma, discrimination, and barriers to care. Finally, the reflections on their attitudes towards transwomen were on five topics Gender affirming care, Healthcare provision for transwomen, Need for further training, New knowledge acquired, and Sexual violence. Nurses attitudes and empathy for vulnerable and key populations improved following the training. Nursing training programs should consider incorporating sexual and gender minority (SGM) specific health training into their curricula to decrease negative attitudes. There is a need to identify best practices and conduct implementation research to provide culturally sensitive and affirming healthcare delivery in sub-Saharan Africa. Future studies should evaluate the effect of provider sensitivity training on sexual health and HIV outcomes for SGM. Furthermore, interventions targeting higher-level stigma, such as structural and policy levels, are critical because they influence interpersonal stigma reduction efforts and initiatives.
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Tuberculosis Preventive Therapy among Persons Living with HIV, Uganda, 2016-2022.
During October 2016-March 2022, Uganda increased tuberculosis (TB) preventive therapy coverage among persons living with HIV from 0.6% to 88.8%. TB notification rates increased from 881.1 to 972.5 per 100,000 persons living with HIV. Timely TB screening, diagnosis, and earlier treatment should remain high priorities for TBHIV prevention programming.
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Effectiveness and safety of tenofovir alafenamide in children and adolescents living with HIV a systematic review.
Tenofovir alafenamide (TAF) is approved for paediatric use in fixed-dose combination tablets, but efficacy and safety data in children are limited. We conducted a systematic review on the efficacyeffectiveness and safety of TAF in infants, children and adolescents living with HIV. We searched MEDLINE, Embase, the Cochrane Library, clinical trial registries, reference lists and relevant conferences to identify literature published January 2009-March 2021. We included clinical trials and observational studies assessing the efficacyeffectiveness or safety of TAF through ≥6 months of treatment in participants aged 0-19 years. Overall 3626 abstracts and 371 full papers were screened. Four single-arm, innovator-funded trials (341 participants) and a pooled analysis of those trials were identified. All four trials included treatment-experienced and virally suppressed children or adolescents. One trial also included treatment-naïve adolescents with baseline viral load >1000 copiesml. The risk of bias was rated as low in one study and unclear in the other three owing to missing data on study design (all conference presentations). At 48 weeks, 92% (4650) of treatment-naïve participants were virally suppressed (one trial). Among treatment-experienced participants with viral load at 48 weeks, 214 of 224 participants were virally suppressed. Across the studies, one grade 34 adverse event was considered drug-related (intermediate uveitis). There were three discontinuations for adverse events (grade 2 anxiety and insomnia, grade 1 iridocyclitis drug-related and grade 1 pulmonary tuberculosis unrelated to treatment). One accidental death occurred across the four studies. In the pooled analysis of 223 participants, the median change in bone mineral density z-score (height- and age-adjusted) from baseline to 48 weeks was -0.12 (interquartile range IQR -0.46, 0.17) to 0.05 (IQR not reported) for spine, and -0.09 (IQR -0.33, 0.07) to 0.09 (IQR not reported) for total body less head. Weight-for-age z-scores increased by 0.25 from baseline to 48 weeks. Four single-arm trials were identified in this systematic review, with initial evidence suggesting good viral suppression and no obvious safety concerns in children and adolescents on TAF-containing regimens over 24-48 weeks. However, further comparative and longer-term safety data are needed in children and adolescents, including on weight and metabolic changes.
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A Census Tract-Level Examination of HIV Care Outcomes and Social Vulnerability Among BlackAfrican American, HispanicLatino, and White Adults in the Southern United States, 2018.
We examined the association between social vulnerability and HIV diagnoses, linkage to HIV medical care, and viral suppression among adults in the Southern U.S. Data from CDCs National HIV Surveillance System (NHSS) were used to determine census tract-level HIV diagnosis rates and percentages of persons linked to care within one month and with viral suppression within six months of diagnosis among BlackAfrican American, HispanicLatino, and White adults aged ≥ 18 years residing in the Southern U.S. in 2018. Census tract-level social vulnerability data were obtained from the 2018 CDC Social Vulnerability Index (SVI). Rate and proportion ratios were used to determine the difference between the lowest quartile of SVI scores (Q1) and the highest quartile (Q4) by age group, transmission category, and region of residence and stratified by sex assigned at birth. Areas with the highest social vulnerability (Q4) had the highest rates of HIV diagnoses (Black 56.5, HispanicLatino 27.2, and White 10.3). Those in Q4 also had the lowest percentages of adults linked to care (Black 76.1%, HispanicLatino 81.2%, and White 77.8%), and the lowest percentages of adults with viral suppression (Black 59.8%, HispanicLatino 68.4%, and White 65.7%). This ecological study found an association between social vulnerability, HIV diagnoses, and poorer care outcomes among BlackAfrican American, HispanicLatino, and White adults. Tailoring interventions and improving access for persons residing in areas with the highest social vulnerability is necessary to reduce HIV transmission and improve health outcomes in the Southern U.S.
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Open-Label, Drug-Drug Interaction Study Between the HIV-1 Maturation Inhibitor GSK3640254 and a Metabolic Probe Cocktail in Healthy Participants.
GSK3640254 (GSK254) is an HIV-1 maturation inhibitor with pharmacokinetics (PK) supporting once-daily dosing. GSK254 will be co-administered with cytochrome P450 enzyme substrates and drug transporters, including other antiretrovirals, in people living with HIV-1 (PLWH). In this open-label study, healthy participants received a single dose of a cocktail of eight cytochrome P450 and transporter probe substrates on Day 1, followed by a 10-day washout before receiving GSK254 200 mg once daily from Days 11 to 20 and a single dose of cocktail GSK254 200 mg on Day 21. Geometric least-squares mean ratios and 90% confidence intervals were obtained using linear mixed-effects models. Adverse events (AEs) were monitored. Of 20 participants enrolled, 19 completed the study. Plasma concentrations of all cocktail substrates were generally similar with or without GSK254 co-administration. All 90% confidence intervals around geometric least-squares mean ratios for cocktail substrate PK parameters indicated no to weak interactions. Steady-state plasma GSK254 concentrations were achieved by Day 17 and maintained through Day 21. Nine participants (45%) reported 17 AEs most (88%) were grade 1. Two grade 2 treatment-related AEs (maculopapular rash leading to withdrawal and papular rash) were reported during GSK254 administration alone. Co-administration of GSK254 with a metabolic probe cocktail in healthy participants indicated very low risk of clinically relevant effect on PK of any substrates or associated metabolites. No new safetytolerability concerns were identified. These results support ongoing phase IIb and planned phase III studies of GSK254 in PLWH.
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Antiretrovirals for Human Immunodeficiency Virus Treatment and Prevention in Pregnancy.
Safe and effective antiretroviral medications are needed during pregnancy to reduce maternal morbidity and mortality associated with untreated human immunodeficiency virus (HIV) infection and to prevent viral transmission to the infant. Pharmacokinetic studies have helped inform the appropriate dosing of antiretroviral medications during pregnancy. However, data from these studies consistently become available years after initial regulatory approvals in nonpregnant adults. In this article, the authors provide an overview of considerations in use of antiretroviral medications in pregnant people with or at risk for HIV, pharmacokinetic studies that helped support recommended options, and therapies either under active investigation or in need of prospective study.
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Mapping the interplay between NK cells and HIV therapeutic implications.
Although highly effective at durably suppressing plasma HIV-1 viremia, combination antiretroviral therapy (ART) treatment regimens do not eradicate the virus, which persists in long-lived CD4 T cells. This latent viral reservoir serves as a source of plasma viral rebound following treatment interruption, thus requiring lifelong adherence to ART. Additionally, challenges remain related not only to access to therapy but also to a higher prevalence of comorbidities with an inflammatory etiology in treated HIV-1 individuals, underscoring the need to explore therapeutic alternatives that achieve sustained virologic remission in the absence of ART. Natural killer (NK) cells are uniquely positioned to positively impact antiviral immunity, in part due to the pleiotropic nature of their effector functions, including the acquisition of memory-like features, and, therefore, hold great promise for transforming HIV-1 therapeutic modalities. In addition to defining the ability of NK cells to contribute to HIV-1 control, this review provides a basic immunologic understanding of the impact of HIV-1 infection and ART on the phenotypic and functional character of NK cells. We further delineate the qualities of memory NK cell populations, as well as the impact of HCMV on their induction and subsequent expansion in HIV-1 infection. We conclude by highlighting promising avenues for optimizing NK cell responses to improve HIV-1 control and effect a functional cure, including blockade of inhibitory NK receptors, TLR agonists to promote latency reversal and NK cell activation, CAR NK cells, BiKEsTriKEs, and the role of HIV-1-specific bNAbs in NK cell-mediated ADCC activity against HIV-1-infected cells.
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Immune recovery among Romanian HIVAIDS patients receiving darunavirritonavir or darunavircobicistat regimens in cART management A three-year study.
Approximately two-thirds of Romanian HIV patients were parenterally infected with the F subtype of HIV in early childhood. They are now in the context of immunological aging, with immunosuppression posing an additional challenge in developing the most effective and well-tolerated regimens. The risk of an improper immune recovery is higher in these patients than in newly diagnosed patients. The primary goal of this retrospective study was to conduct a comparative analysis of the immune recovery, measured at three time points, on 462 HIV-infected patients who were registered at the Matei Balş National Institute of Infectious Diseases, Bucharest, Romania, between 2018 and 2021, as follows darunavir (DRV) 600 mg plus ritonavir (RTV) 100 mg (twice daily) was given to 384 patients, while DRV 800 mg plus cobicistat (COBI) 150 mg was given to 78 patients (once daily). The immune response was assessed by counting T lymphocytes, CD4 count cellsmm
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Pathways connecting socioeconomic marginalization and overdose A qualitative narrative synthesis.
This qualitative narrative synthesis sought to identify pathways connecting socioeconomic marginalization (SEM) and overdose for people who use drugs. We included studies with qualitative examination of SEM and fatal and non-fatal overdose published in English between 2000 and 2021. Studies were systematically identified and screened by searching MEDLINE (Ovid), Embase (Ovid), PsycINFO (EBSCOhost), CINAHL (EBSCOhost), Google Scholar, Cochrane Central Registry of Controlled Trials (CENTRAL), and Cochrane Drug and Alcohol Group (CDAG) Specialized Registry, citations, and contacting experts. Risk of bias and quality assessments were performed using the Critical Appraisal Skills Programme checklist and the Confidence in the Evidence from Reviews of Qualitative Research approach. Data were synthesized using a thematic synthesis approach. The primary search strategy found 5909 articles that met the initial screening criteria. The review and screening process led to a final dataset of 27 qualitative articles. The four key findings of this narrative synthesis revealed aspects of SEM which shaped drug poisoning risk for people who use drugs (1) resource insufficiency, labor market exclusion and deindustrialization, (2) homelessness and housing, (3) policing, criminalization, and interactions with emergency services, and (4) gendered and racialized dimensions of inequality. Findings led to creating a typology that includes material, behavioral, psychological, social, and environmental pathways that contain multiple mechanisms connecting SEM to overdose. This review revealed reciprocal connections between overdose and SEM via institutional pathways with reinforcing mechanisms, and interrelationships present within and between pathways. Quality assessments indicated moderate confidence in three of four findings (Findings 2,3, and 4 above) and high confidence in one finding (Finding 1). SEM is strongly linked to drug poisoning, and the mechanisms establishing these connections can be classified within four pathways. The interconnectedness of these mechanisms can lead to intensification of overdose risk and reinforcement of SEM itself.
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Comparative efficacy and acceptability of non-pharmacological interventions for depression in people living with HIV A systematic review and network meta-analysis.
Treatment for depression in people living with HIV has increasingly turned to non-pharmacological treatments due to the adverse reactions of pharmacotherapy. However, it remains unclear which non-pharmacological treatment is the most effective and acceptable for depression in people living with HIV. To compare and rank the efficacy and acceptability of different non-pharmacological treatments for depression in people living with HIV. A systematic review and Bayesian network meta-analysis. We systematically searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, PsycArticles, CINAHL, ProQuest, OpenGrey, and international trial registers for published and unpublished studies from their inception to September 1, 2022, and searched key conference proceedings from January 1, 2020, to September 25, 2022. We searched for randomized controlled trials of any non-pharmacological treatments for depression in adults living with HIV (≥18 years old). Primary outcomes were efficacy (mean change scores in depression) and acceptability (all-cause discontinuation). We used a random-effects network meta-analysis model to synthesize all available evidence. The methodological quality of the included studies was assessed using the Cochrane Collaboration Risk of Bias Tool. We registered this study in PROSPERO, number CRD42021244230. A total of 53 randomized controlled trials were included in this network meta-analysis involving seven non-pharmacological treatments for depression in people living with HIV. For efficacy, mind-body therapy, interpersonal psychotherapy, cognitive-behavioral therapy, supportive therapy, and education were significantly more effective than most control conditions (standardized mean differences ranged from -0.96 to -0.36). Rankings probabilities indicated that mind-body therapy (79%), interpersonal psychotherapy (71%), cognitive-behavioral therapy (62%), supportive therapy (57%), and education (57%) might be the top five most significantly effective treatments for depression in people living with HIV, in that order. For acceptability, only supportive therapy and interpersonal psychotherapy were significantly less acceptable than most control conditions (odds ratios ranged from 1.92 to 3.43). Rankings probabilities indicated that education might be the most acceptable treatment for people living with HIV (66%), while supportive therapy (26%) and interpersonal psychotherapy (10%) might rank the worst. The GRADE assessment results suggested that most results were rated as moderate to very low for the confidence of evidence. Our study confirmed the efficacy and acceptability of several non-pharmacological treatments for depression in people living with HIV. These results should inform future guidelines and clinical decisions for depression treatment in people living with HIV.
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Deadly mpox risk in people with untreated HIV comes into view.
Analysis of hundreds of patients suggests mpox is a different disease in immunocompromised patients.
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Supernatural beliefs, religious affiliations, and HIV testing among recently arrived Asian-born men who have sex with men in Australia.
HIV testing rates among recently arrived (≤5 years) Asian-born men who have sex with men (MSM) in Australia remain suboptimal. Research indicates that belief in supernatural determinants of health (supernatural beliefs) may be an important barrier to greater HIV test uptake. We examined potential associations between supernatural beliefs and HIV testing among recently arrived Asian-born MSM in Australia. In 2019, an online survey was completed by 186 self-identified MSM born in Asia, and who arrived in Australia within the past five years and were never diagnosed with HIV. Supernatural belief was measured as the extent to which one felt that health was influenced by supernatural forces. Measures of association were estimated with multiple logistic regression. Participants with supernatural beliefs were significantly less likely to have tested for HIV in the past year. The adjusted predicted probability of not testing for HIV in the past year was 44.8% among those who held supernatural beliefs (95% CI 30.5-59.2%), but only 5.2% among those who did not hold supernatural beliefs (95% CI 1.9-8.6%). Religious affiliation was not significantly associated with testing for HIV. Supernatural beliefs may be an important but underappreciated barrier to HIV testing among recently arrived Asian-born MSM in Australia.
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Emergency department experiences of people who use drugs who left or were discharged from hospital against medical advice.
People who use drugs (PWUD) frequent emergency departments at a higher rate than the general population, and experience a greater frequency of soft tissue infections, pneumonia, and chronic conditions such as, HIVAIDs and hepatitis C. This population has distinct health care considerations (e.g. withdrawal management) and are also more likely to leave or be discharged from hospital against medical advice. This study examines the experiences of PWUD who have left or been discharged from hospital against medical advice to understand the structural vulnerabilities that shape experiences with emergency departments. Semi-structured qualitative interviews were conducted with 30 PWUD who have left or been discharged from hospital against medical advice within the past two years as part of a larger study on hospital care and drug use in Vancouver, Canada. Findings characterize the experiences and perceptions of PWUD in emergency department settings, and include (1) stigmatization of PWUD and compounding experiences of discrimination (2) perceptions of overall neglect (3) inadequate pain and withdrawal management and (4) leaving ED against medical advice and a lack of willingness to engage in future care. Structural vulnerabilities in ED can negatively impact the care received among PWUD. Findings demonstrate the need to consider how structural factors impact care for PWUD and to leverage existing infrastructure to incorporate harm reduction and a structural competency focused care. Findings also point to the need to consider how withdrawal and pain are managed in emergency department settings.
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Increased uptake of tuberculosis preventive therapy (TPT) among people living with HIV following the 100-days accelerated campaign A retrospective review of routinely collected data at six urban public health facilities in Uganda.
Tuberculosis preventive therapy (TPT) effectively decreases rates of developing active tuberculosis disease in people living with HIV (PLHIV) who are at increased risk. The Uganda Ministry of Health launched a 100-day campaign to scale-up TPT in PLHIV in July 2019. We sought to examine the effect of the campaign on trends of TPT uptake and characteristics associated with TPT uptake and completion among persons in HIV care. We retrospectively reviewed routinely collected data from 2016 to 2019 at six urban public health facilities in Uganda. HIV care database and paper-based TPT registers at six public health facilities in Kampala, Uganda were retrospectively reviewed. Estimated trends of TPT (given as Isoniazid monotherapy) uptake and completion across the 4 years, among PLHIV aged 15 years and above, and factors associated, were examined using Poisson regression model with robust standard errors using generalized estimating equation (GEE) models. On average, a total of 39,774 PLHIV aged 15 years and above were eligible for TPT each calendar year at the six health facilities. Across all 4 years, more than 70% were females (range 73.5% -74.6%) and the median age ranged from 33 to 34 years. From 2016 quarter one to 2019 quarter two, TPT uptake was consistently below 25%, but, as expected, the uptake significantly increased by about 3-folds from 22.1% to 61.2%, in 2019 quarter two (i.e. before the roll-out of the 100-day accelerated TPT intervention) and quarter three (i.e. after the roll-out of the 100-day accelerated TPT intervention) respectively. This increase remained highly significant even after adjusting for patients baseline characteristics (adjusted prevalence ratio aPR 2.58 95%CI 2.45, 2.72, P-value<0.001). TPT completion was consistently high at above 70% at most of the time, but, it increased significantly among those initiated during 2018 quarter four and in the subsequent two quarters after the roll-out of the 100-day accelerated TPT intervention (i.e. TPT completion was 83.2%, 95.3%, and 97.1% among individuals initiated during 2018 quarter4, and 2019 quarters 1 and 2, respectively). The increase in TPT completion during this period remained significant even after adjusting for patients baseline characteristics (aPR 95%CI 1.09 1.04, 1.14, P value<0.001, and 1.10 1.05,1.15, P value<0.001, for individuals initiated during 2019 quarter 1, and 2, respectively compared to those initiated during 2018 quarter 4). Not on ART or newly started on ART compared to ART experienced, and pregnant at TPT initiation compared to not pregnant were associated with poor TPT completion, whereas older age (≥25 years versus 15-24 years) was associated with higher TPT completion. The targeted 100-day campaign dramatically increased TPT uptake and completion among PLHIV suggesting a viable catch up strategy to meet WHO guidelines. Future analysis with additional years of data post 100-days TPT intervention is required to evaluate the sustainability of the observed gains.
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HIV virologic response, patterns of drug resistance mutations and correlates among adolescents and young adults A cross-sectional study in Tanzania.
The emergence of HIV drug resistance mutations (DRMs) is of significant threat to achieving viral suppression (VS) in the quest to achieve global elimination targets. We hereby report virologic outcomes and patterns of acquired DRMs and its associated factors among adolescents and young adults (AYA) from a broader HIV drug resistance surveillance conducted in Tanzania. Data of AYA was extracted from a cross-sectional study conducted in 36 selected facilities using a two-stage cluster sampling design. Dried blood spot (DBS) samples were collected and samples with a viral load (VL) ≥1000 copiesmL underwent genotyping for the HIV-1 pol gene. Stanford HIV database algorithm predicted acquired DRMs, Fishers exact test and multivariable logistic regression assessed factors associated with DRMs and VS, respectively. We analyzed data of 578 AYA on antiretroviral therapy (ART) for 9-15 and ≥ 36 months among them, 91.5% and 88.2% had VS (VL<1000copiesmL) at early and late time points, respectively. Genotyping of 64 participants (11.2%) who had VL ≥1000 copiesml detected 71.9% of any DRM. Clinically relevant DRMs were K103N, M184V, M41L, T215YF, L210WL, K70R, D67N, L89VT, G118R, E138K, T66A, T97A and unexpectedly absent K65R. Participants on a protease inhibitor (PI) based regimen were twice as likely to not achieve VS compared to those on integrase strand transfer inhibitors (INSTI). The initial VL done 6 months after ART initiation of ≥1000copiesmL was the primary factor associated with detecting DRMs (p .019). VS amongst AYA is lower than the third UNAIDs target. Additionally, a high prevalence of ADR and high levels of circulating clinically relevant DRMs may compromise the long-term VS in AYA. Furthermore, the first VL result of ≥1000copiesml after ART initiation is a significant risk factor for developing DRMs. Thus, strict VL monitoring for early identification of treatment failure and genotypic testing during any ART switch is recommended to improve treatment outcomes for AYA.
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Maternal biomarkers of endothelial dysfunction and pregnancy outcomes in women with and without HIV in Botswana.
Women living with HIV-1 (WLHIV) are at higher risk of having an adverse birth outcome, but the underlying mechanism(s) are unknown. We hypothesized that HIV-associated endothelial activation could adversely impact placental function and lead to impaired fetal growth or stillbirth. We used stored samples from WLHIV and HIV-negative women who had enrolled during pregnancy in the observational Botswana Tshipidi cohort. Written informed consent was obtained from the participants. We measured plasma levels of markers of endothelial activation (soluble vascular adhesion molecule 1 VCAM-1, intercellular adhesion molecule 1 ICAM-1 and E-selectin) from samples taken during pregnancy. We compared log10 biomarker levels by maternal HIV status and by the timing of ART initiation (ART prior to conception vs. during pregnancy ART prior to sample collection vs. no ART prior to sampling) using t-tests and the Kruskal-Wallis rank test. We evaluated the association between these biomarkers and adverse birth outcomes (composite of stillbirth or small for gestational age SGA) using univariate and multivariate log-binomial regression controlling for maternal age (continuous) and timing of ART start. We also used generalized linear models (GLM) to evaluate the association between continuous birthweight (in grams) and gestational age (in weeks) and markers of endothelial dysfunction, adjusting for maternal age (continuous) and timing of ART relative to sample collection. Specimens collected before delivery were available for 414 women (372 WLHIV and 42 HIV-negative women), with a median age of 28 years and median gestational age at sample collection of 30 weeks (range 26, 35 weeks). WLHIV had significantly higher median VCAM1 (p 0.002) than HIV-negative women, but HIV-negative women had higher median ICAM1 (p 0.01) e-Selectin levels did not differ by maternal HIV status. Women starting ART during pregnancy had higher log10 VCAM1 levels than those on ART before conception, regardless of whether the sample was collected before (p 0.02) or after (p 0.03) ART initiation. However, ICAM1 and e-Selectin did not differ significantly by ART status or ART timing. Ninety-eight women (91 WLHIV and 7 HIV-negative), or 9 (2%) and 89 (22%) included in this study, had a stillborn or SGA baby respectively. Univariate and adjusted analyses did not show significant associations between levels of any of the biomarkers with these adverse birth outcomes. However, lower birthweight (p 0.03) and lower gestational age at delivery were associated e-Selectin and ICAM (p 0.008), respectively. Maternal HIV infection and lack of ART (or recent ART initiation) were associated with one marker of greater endothelial activation (VCAM-1), but not with other markers (ICAM-1 nor E-selectin) in pregnancy. e-Selectin was associated with lower birthweight and every unit increase in log ICAM-1 at delivery was associated with lower gestation age at delivery.
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Cryptococcal Meningitis and Clinical Outcomes in Persons with HIV A Global View.
Cryptococcal meningitis (CM) is a major cause of morbidity and mortality in persons with HIV(PWH). Little is known about CM outcomes and availability of diagnostic and treatment modalities globally. This retrospective cohort study investigated CM incidence and all-cause mortality after CM diagnosis in PWH in the IeDEA cohort from 1996-2017. We estimated overall and region-specific incidence and incidence rate ratios using quasi-Poisson models adjusted for sex, age, calendar year, time-updated CD4, and time-updated antiretroviral therapy (ART) status. Mortality after CM diagnosis was examined using multivariable Cox models. A site survey from 2017 assessed availability of CM diagnostic and treatment modalities. Among 518,852 PWH, there were 3,857 diagnosed cases of CM with an estimated incidence of 1.54 per 1000 person-years. Mortality over a median of 2.6 years of post-CM diagnosis follow-up was 31.6%, with 29% lost to follow-up. 2,478 (64%) were diagnosed with CM after ART start with a median of 253 days from ART start to CM diagnosis. Older age (HR 1.31 for 50 vs 35 years 95%CI 1.12-1.53), lower CD4 (HR 1.15 for 200 vs 350 cellsmm3 95%CI 1.03-1.30), and earlier year of CM diagnosis (HR 0.51 for 2015 vs 2000 95%CI 0.37-0.70) were associated with higher mortality. Of 89 sites, 34% reported access to amphotericin B 12% had access to flucytosine. Mortality after CM diagnosis was high. A substantial portion of CM cases occurred after ART start, though incidence and mortality may be higher than reported due to ascertainment bias. Many sites lacked access to recommended CM treatment.
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IL15 enhances HIV-1 infection by promoting survival and proliferation of CCR5CD4 T cells.
HIV-1 usually utilize CCR5 as the co-receptor and rarely switches to CXCR4-tropic until late stage of infection. CCR5CD4 T cells are the major virus-producing cells in viremic patients as well as SIV-infected non-human primates. The differentiation of CCR5CD4 T cells is associated with the availability of IL15, which increases during acute HIV-1 infection. Here, we report that CCR5 is expressed by CD4 T cells exhibiting effector or effector memory phenotype with high expression levels of the IL2IL15 receptor common beta and gamma chains. IL15 but not IL7 improves the survival of CCR5CD4 T cells, drives their expansion, and facilitates HIV-1 infection in vitro and in humanized mice. Our study suggests that IL15 plays confounding roles in HIV-1 infection, and future studies on the IL15-based boosting of anti-HIV-1 immunity should carefully exam the potential effects on the expansion of HIV-1 reservoirs in CCR5CD4 T cells.
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Mobile Phone Apps for HIV Prevention Among College-Aged Black Women in Atlanta Mixed Methods Study and User-Centered Prototype.
Black women in college are disproportionately affected by HIV diagnoses. Mobile apps can facilitate the innovative delivery of accurate HIV and sexual and reproductive health information. However, mobile health interventions are severely underused in this population. We aimed to quantitatively and qualitatively explore the perspectives of college-aged Black women on using a mobile health app for HIV prevention and sexual and reproductive health. The data obtained from Black women were used to design preliminary mobile app wireframes and features. This explanatory, sequential mixed methods study took place from 2019 to 2020 and targeted Black women who were enrolled in college or who had recently graduated from college. Convenience sampling was used during the quantitative phase, followed by purposive sampling in the qualitative phase. A cross-sectional web-based survey evaluating the willingness to use a mobile app for HIV prevention was conducted in the quantitative phase. Descriptive statistics were used for all variables. A separate focus group discussion was conducted with Black women in college to expand on the quantitative results. Focus group discussions explored their perceptions on HIV and health content delivered through a mobile app along with potential features that participants desired within the app. Using the data obtained, we selected the primary features for the app prototype. In total, we enrolled 34 participants in the survey, with 6 participating in focus group discussions. Over half of the respondents reported a willingness to use an app that contained pre-exposure prophylaxis content. Women who claimed recent sexual activity reported being more likely to use an app feature that would allow them to order an at-home HIV testing kit than their non-sexually active counterparts. The emerging themes from the focus group session were Black womens health concerns, HIV risk, sources of health information, and preferred app features. The content in our prototype included speaking with a specialist, HIV and pre-exposure prophylaxis information, holistic wellness, and features promoting engagement and retention. The results of our study guided the design of wireframes for an app prototype targeting HIV prevention in college-aged Black women. The rapid growth of mobile devices in Black communities, coupled with high rates of smartphone ownership among Black youth, makes mobile health interventions a promising strategy for addressing sexual and reproductive health disparities. Participants in our sample were willing to use a culturally appropriate and gender-considerate app for their sexual health needs. Our findings indicate that Black women in college may be excellent candidates for mobile app-based interventions.
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Anti-GM-CSF Neutralizing Autoantibodies in Colombian Patients with Disseminated Cryptococcosis.
Cryptococcosis is a potentially life-threatening fungal disease caused by encapsulated yeasts of the genus Cryptococcus, mostly C. neoformans or C. gattii. Cryptococcal meningitis is the most frequent clinical manifestation in humans. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been discovered in otherwise healthy adult patients with cryptococcal meningitis, mostly caused by C. gattii. We hypothesized that three Colombian patients with cryptococcal meningitis caused by C. neoformans in two of them would carry high plasma levels of neutralizing auto-Abs against GM-CSF. We reviewed medical and laboratory records, performed immunological evaluations, and tested for anti-cytokine auto-Abs three previously healthy HIV-negative adults with disseminated cryptococcosis. Peripheral blood leukocyte subset levels and serum immunoglobulin concentrations were within the normal ranges. We detected high levels of neutralizing auto-Abs against GM-CSF in the plasma of all three patients. We report three Colombian patients with disseminated cryptococcosis associated with neutralizing auto-Abs against GM-CSF. Further studies should evaluate the genetic contribution to anti-GM-CSF autoantibody production and the role of the GM-CSF signaling pathway in the immune response to Cryptococcus spp.
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Accelerated epigenetic aging in older adults with HIV disease associations with serostatus, HIV clinical factors, and health literacy.
The prevalence of older persons with HIV (PWH) disease has increased considerably in the last 20 years, but our understanding of biological factors of aging and their clinical correlates among PWH remains limited. Study participants were 149 persons aged 50 and older, including 107 PWH and 42 seronegatives. All participants completed a blood draw, research medical evaluation, structured psychiatric interview, neurocognitive assessment, questionnaires, and measures of health literacy. Four epigenetic clocks were generated from stored blood samples using standardized laboratory methods. In regression models adjusting for sex and smoking status, PWH had significantly higher epigenetic aging acceleration values than seronegatives on all four indicators. Within the PWH sample, higher levels of epigenetic aging acceleration were moderately associated with lower current CD4 count, AIDS diagnoses, higher scores on the Veterans Aging Cohort Study Index, and lower telomere values. Higher epigenetic aging acceleration indices were also associated with lower health literacy among PWH. PWH experience accelerated aging as measured by a series of epigenetic clocks, which may be linked to immune compromise and risk of all-cause mortality. Health literacy may be a modifiable target for mitigating the risk of accelerated aging among older PWH.
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RELA tunes innate-like interferon IIII responses in human T cells.
In innate immune cells, intracellular sensors such as cGAS-STING stimulate type IIII interferon (IFN) expression, which promotes antiviral defense and immune activation. However, how IFN-IIII expression is controlled in adaptive cells is poorly understood. Here, we identify a transcriptional rheostat orchestrated by RELA that confers human T cells with innate-like abilities to produce IFN-IIII. Despite intact cGAS-STING signaling, IFN-IIII responses are stunted in CD4 T cells compared with dendritic cells or macrophages. We find that lysine residues in RELA tune the IFN-IIII response at baseline and in response to STING stimulation in CD4 T cells. This response requires positive feedback driven by cGAS and IRF7 expression. By combining RELA with IRF3 and DNA demethylation, IFN-IIII production in CD4 T cells reaches levels observed in dendritic cells. IFN-IIII production provides self-protection of CD4 T cells against HIV infection and enhances the elimination of tumor cells by CAR T cells. Therefore, innate-like functions can be tuned and leveraged in human T cells.
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Epidemiology of Herpes Zoster in the pre-vaccination era establishing the baseline for vaccination programmes impact in Spain.
BackgroundHerpes zoster (HZ) affects 1 in 3 persons in their lifetime, and the risk of HZ increases with increasing age and the presence of immunocompromising conditions. In Spain, vaccination guidelines were recently updated to include the recommendation of the new recombinant zoster vaccine (RZV) for certain risk groups.AimTo describe the epidemiology of HZ-related hospitalisations in Spain in order to prioritise vaccination recommendations and define a baseline to monitor the effectiveness of vaccination policies.MethodsRetrospective study using the National Health Systems Hospital Discharge Records Database, including all HZ-related hospitalisations from 1998 to 2018.ResultsThe 65,401 HZ-related hospitalisations, corresponded to an annual mean hospitalisation rate of 6.75 per 100,000 population. There was an increasing trend of HZ hospitalisations over the study period. This rate was higher in males and older age groups, particularly over 65 years. Comorbidities with higher risk of readmission were leukaemialymphoma (RR 2.4 95% CI 2.3-2.6) and solid malignant neoplasm (RR 2.2 95% CI 2.1-2.4). Comorbidities associated with higher risk of mortality were leukaemialymphoma (RR 2.9 95% CI 2.7-3.2), solid malignant neoplasm (RR 2.9 95% CI 2.7-3.1) and HIV infection (RR 2.2 95% CI 1.8-2.7).ConclusionOf all patients hospitalised with HZ, those with greater risk of mortality or readmission belonged to the groups prioritised by the current vaccination recommendations of the Spanish Ministry of Health. Our study provided relevant information on clinical aspects of HZ and established the base for future assessments of vaccination policies.
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Resilience during the COVID-19 pandemic among people living with HIV A cross-sectional study.
This study aims to investigate the factors shaping resilience during the COVID-19 pandemic among people living with HIV (PLWH). A total of 341 participants were included in this cross-sectional study. The online survey included scales of resilience, depression anxiety, loneliness, social support, COVID-19 fear, stress, and sociodemographic information. Logistic regression test results showed loneliness (OR 2.548, 95% CI 1.251, 5.189), social support (OR 2.217, 95% CI 1.148, 4.279), income (OR 2.581, 95% CI 1.217, 5.472), sexual orientation (OR 2.707, 95% CI 1.004, 7.300), age (OR 1.044, 95% CI 1.006, 1.083) and COVID-19 fear (OR 0.891, 95% CI 0.840, 0.944) were statistically significant factors associated with resilience among PLWH. In conclusion, reducing COVID-19 fear by providing the correct information about the COVID-19 pandemic, fortifying the level of social support satisfaction, as well as minimising the level of loneliness have the potential to improve psychological resilience among PLWH.
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Radiation Treatment for Cancer of the Anal Margin.
To identify best treatment practices by examining outcomes of anal margin cancer patients treated with radiotherapy. Relevant literature was compared with 38 patients at our institution treated 1979 to 2019 with curative radiotherapy. Median age was 51. Four patients had T1, 22 had T2, and 12 had T3 disease based on the American Joint Committee on Cancer (AJCC) staging at time of diagnosis. Nodal staging distribution was N033 N12 N22 N31. Median radiation dose was 56 Gy30 fractions. Five received nodal radiation for node positivity, 29 received elective nodal radiation, and 29 had perineal boost. Twenty-seven received concurrent chemotherapy. Three patients experienced isolated local recurrence, 2 had isolated inguinal node recurrences, and 2 developed distant metastases, 1 of whom also had local and regional recurrence. Ten-year disease-free survival (DFS), cause-specific survival, and overall survival were 87%, 92%, and 68%, respectively. One patient did not complete radiation, and 4 had unexpected treatment breaks. Two received salvage abdominoperineal resections. At last follow-up, 17 were alive with no evidence of disease, 2 were alive with anal margin cancer present, 3 had died with anal margin cancer present at 11, 18, and 21 months from radiation therapy, and 16 had died from intercurrent disease. Median follow-up was 6.6 years (range 0.9 to 29.0 y). Age ≥51 was associated with worse locoregional control (P0.018) and DFS (P0.0233), males had worse DFS (P0.0311), and HIV-positive patients had worse overall survival (P0.006). Radiation provides high locoregional control of anal margin cancer with good long-term outcomes.
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Severe Acute Respiratory Syndrome Coronavirus 2 Evolution and Escape From Combination Monoclonal Antibody Treatment in a Person With HIV.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) escape from combination monoclonal antibody treatment is rarely reported. We describe an immunocompromised individual with human immunodeficiency virus and persistent SARS-CoV-2 infection in whom substantial SARS-CoV-2 evolution occurred, including the emergence of 2 mutations associated with escape from the monoclonal antibody cocktail received.
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Epidemiological characteristics and real-world treatment outcomes of hepatitis C among HIVHCV co-infected patients in Myanmar A prospective cohort study.
In Myanmar, public sector treatment programs for hepatitis C virus (HCV) infection were nonexistent until June 2017. WHO highlights the importance of simplification of HCV service delivery through task-shifting among health workers and decentralization to the primary health care level. Between November 2016 and November 2017, a study was conducted to describe the epidemiological data and real-world outcomes of treating HIVHCV coinfected patients with generic direct acting antiviral (DAA) based regimens in the three HIV clinics run by nonspecialist medical doctors in Myanmar. HCV co-infection among people living with HIV (PLHIV) from two clinics in Yangon city and one clinic in Dawei city was screened by rapid diagnostic tests and confirmed by testing for viral RNA. Nonspecialist medical doctors prescribed sofosbuvir and daclatasvir based regimens (with or without ribavirin) for 12 or 24 weeks based on the HCV genotype and liver fibrosis status. Sustained virologic response at 12 weeks after treatment (SVR12) was assessed to determine cure. About 6.5% (141721,777) of PLHIV were co-infected with HCV. Of 864 patients enrolled in the study, 50.8% reported history of substance use, 27% history of invasive medical procedures and 25.6% history of incarceration. Data on treatment outcomes were collected from 267 patients of which 257 (96.3%) achieved SVR12, 7 (2.6%) failed treatment, 2 (0.7%) died and 1 (0.4%) became loss to follow-up. The study results support the integration of hepatitis C diagnosis and treatment with DAA-based regimens into existing HIV clinics run by nonspecialist medical doctors in a resource-limited setting. Epidemiological data on HIVHCV co-infection call for comprehensive HCV care services among key populations like drug users and prisoners in Yangon and Dawei.
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Sexual Health and Sexual Quality of Life Among Individuals With Spinal Cord Injury in Latin America.
Sexual changes are an area of primary concern for individuals with spinal cord injury (SCI) and their partners, but the topic has gone largely unexplored in the research literature. This study examined how individuals with SCI in Latin America experience their sexuality and what issues they and their partners face in this area. A total of 248 individuals with SCI from Latin America completed an online 60-item survey regarding sexuality. The majority of participants (87.7%) reported that they had noticed changes in sexuality after the injury, mainly physical problems (50.7%), emotional problems (38.7%), and changes in relationships with partners (27.5%). Regarding sexual desire, 47.2% indicated that desire remained the same after SCI. The majority of participants (81.9%) indicated not having received any information about sexuality after SCI during their hospital stay but reported that they would have liked to have received information (98.1%). Of all participants, 66.1% reported never having been asked about problems or difficulties in their sexual life after SCI by any health professional. Interventions designed to educate individuals with SCI regarding the effect of injury on their sexual functioning, responsiveness, and expression, as well as to support them in maintaining and enhancing their sexual well-being, may be extremely beneficial, particularly in Latin America. Findings highlight the distinct need for professionals to introduce the topic of sexuality by discussing it in a straightforward, nonjudgmental manner and to integrate discussions about sex and related issues into assessment, planning, and ongoing treatment.
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Achieving the cancer moonshot in Africa.
For decades now, the United States (US) has been a leading contributor in global health with the government, academic institutions, foundations, non-profits and industry investing and partnering with African countries, as seen with the US Presidents Emergency Plan for AIDS Relief (PEPFAR) program. Now as more people survive HIVAIDs and other infectious diseases in Africa and live longer, non-communicable diseases like cancer are on the rise, in what can be described as a growing health iceberg, hidden under epidemics of infectious diseases. There is now more urgent need for international collaborations on cancer, which has become a leading cause of death in both Africa and the US, underpinned by poignant disparities in access to care. The re-ignited Cancer Moonshot in the USA and publication of the Lancet Oncology Commission report for sub-Saharan Africa in 2022 provide a timely and valuable framework for growing US-Africa collaborations in the coming years towards attaining the goal of the cancer moonshot both in the US and Africa. This goal is to reduce cancer death rate by at least 50% over the next 25 years, and to improve the experience of those living with and surviving cancer. The US-Africa summit taking place in Washington in December 2022 provides a momentous opportunity to identify recommendations or priority areas, some of them included in this article, and initiating action for win-win collaborations towards achieving the cancer moonshot in Africa.
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null
Human immunodeficiency virus (HIV) is an infectious virus that depletes the CD4
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Malignant Syphilis A Rare Case of Early Secondary Syphilis in an Immunocompetent Patient.
Early malignant syphilis is an uncommon form of secondary syphilis and characterized by pleomorphic multiple round-to-oval papules, some with necrosis, and associated with systemic signs and symptoms. Usually seen in immunosuppressed patients, mainly those infected with HIV, it can also be observed in immunocompetent patients. We report a case in a young healthy woman with the characteristic features of the disease and with favourable skin lesion evolution after appropriate treatment with penicillin. Skin lesions can be caused by numerous systemic diseases.Syphilis is the great mimicker and should always be considered as a diagnosis in those with skin lesions.
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Complex Case Management of Mycobacterium Tuberculosis Extrapulmonary Manifestation to the Right Sacroiliac Joint.
While Mycobacterium tuberculosis is a common bacterial pathogen that infects the respiratory system, especially in endemic regions, it may uncommonly manifest in other organ systems, such as the nervous, gastrointestinal, or musculoskeletal systems. Sacroiliac joint infections are rare, and only 1%-5% of all infections are tuberculous in nature. Given nonspecific inflammatory signs in both laboratory and radiologic examinations, early identification of the causative agent can be difficult. In this report, we present the case of a 29-year-old Eritrean woman who presented with an uncommon extrapulmonary tuberculosis manifestation of the right sacroiliac joint. The patient reported pain for two years before a formal diagnosis with multiple computed tomography scans demonstrated fluid collections about her right hip and thigh. The patients medical history of developmental delay, psychosis, outdated medication documentation, non-therapeutic use of numerous psychiatric medications contraindicated for traditional anti-tubercular therapy, and socioeconomic history of a lack of social support and treatment arrangements with the patients caregiver all complicated the treatment course. Given the rise in tuberculosis cases worldwide and vulnerability factors in patients with mental illnesses such as poverty, homelessness, diabetes, and HIV infection that can predispose patients to tuberculosis infections, early diagnosis and treatment are essential to reduce long-term consequences and improve clinical outcomes. Further research in the development of new tuberculosis treatment plans is essential to addressing an equitable treatment course alongside fighting against the recent rise in drug-resistant tuberculosis.
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HIV-associated Burkitt lymphoma in the combination antiretroviral therapy era Real-world outcomes and prognostication.
We performed a retrospective study to analyze the clinical characteristics and outcomes of human immunodeficiency virus-associated Burkitts lymphoma in Chongqing University Cancer Hospital, southwest China, from March 2012 to February 2022. In the entire cohort, the median age was 36 years (range, 28-60 years), and more patients were male (82.4%). The median CD4
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Prevalence and risk factors for subclinical atherosclerosis amongst adults living with HIV in University of Abuja Teaching Hospital, Gwagwalada.
Subclinical atherosclerosis characterizes cardiovascular diseases (CVD), and Human Immunodeficiency Virus (HIV) infection and antiretroviral therapy (ART) are identified risk factors for atherosclerosis. Meanwhile, data on HIV and atherosclerosis in Nigeria are limited. We sought to estimate the prevalence of subclinical atherosclerosis and associated risk factors amongst adult persons living with HIVAIDS (PLHIV) enrolled at University of Abuja Teaching Hospital, Gwagwalada, Abuja (UATH). This was a cross-sectional study of 277 consecutively selected PLHIV ≥18 years enrolled for HIV care and treatment at UATH. Pretested structured questionnaire was used to collect data from consenting ART-experienced and ART-naïve patients on risk factors of atherosclerosis. Carotid intima media thickness (CIMT) ≥0.71 mm as measured by Doppler ultrasonography was used to identify patients with sub-clinical atherosclerosis. Two logistic regression models with (Model-A) and without (Model-B) traditional risk factors were fitted to identify risk factors of subclinical atherosclerosis. Participants mean age was 39.44 ± 10.71 years with female preponderance (64.26%). Overall prevalence of subclinical atherosclerosis was 43.32% (62.25% in ART-experienced). Model-A identified male sex AOR 4.33(1.74-10.76), Subclinical atherosclerosis was higher in ART-experienced patients, and this was irrespective of presence or absence of traditional risk factors. And advancing HIV disease and duration on ART were found as significant risk factors for subclinical atherosclerosis. We therefore recommend routine CVD risk screening in PLHIV.
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Benign lymphoepithelial cyst of parotid gland without human immunodeficiency virus infection A case report.
Benign lymphoepithelial cyst (BLEC) of the parotid gland is a rare benign embryonic-dysplastic cystic tumor in the anterolateral neck that occurs most commonly in human immunodeficiency virus (HIV)-positive adults and rarely in non-acquired immune deficiency syndrome patients. The main presentation is a slow-growing, painless mass, and secondary infection may cause acute inflammatory symptoms. A 44-year-old Chinese male patient presented with a 1-year history of a mass in the left side of the neck. On physical examination, a mass similar in size and shape to a quail egg was found in the left parotid gland. The mass was tough, without tenderness, and easily moveable. The results of HIV tests, including antibody and nucleic acid tests and CD4 T cell examination, were negative. Imaging examination revealed a left parotid gland mass. The patient underwent surgical treatment, and BLEC was diagnosed based on postoperative pathology. After 2 years of follow-up, the patient survived well without related discomfort. The detailed characteristics of a BLEC in a patient without HIV infection contribute to an improved understanding of this rare disease.
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HIV Nef Expression Down-modulated GFAP Expression and Altered Glutamate Uptake and Release and Proliferation in Astrocytes.
HIV infection of astrocytes leads to restricted gene expression and replication but abundant expression of HIV early genes Tat, Nef and Rev. A great deal of neuroHIV research has so far been focused on Tat protein, its effects on astrocytes, and its roles in neuroHIV. In the current study, we aimed to determine effects of Nef expression on astrocytes and their function. Using transfection or infection of VSVG-pseudotyped HIV viruses, we showed that Nef expression down-modulated glial fibrillary acidic protein (GFAP) expression. We then showed that Nef expression also led to decreased GFAP mRNA expression. The transcriptional regulation was further confirmed using a GFAP promoter-driven reporter gene assay. We performed transcription factor profiling array to compare the expression of transcription factors between Nef-intact and Nef-deficient HIV-infected cells and identified eight transcription factors with expression changes of 1.5-fold or higher three up-regulated by Nef (Stat1, Stat5, and TFIID), and five down-regulated by Nef (AR, GASISRE, HIF, Sp1, and p53). We then demonstrated that removal of the Sp1 binding sites from the GFAP promoter resulted in a much lower level of the promoter activity and reversal of Nef effects on the GFAP promoter, confirming important roles of Sp1 in the GFAP promoter activity and for Nef-induced GFAP expression. Lastly, we showed that Nef expression led to increased glutamate uptake and decreased glutamate release by astrocytes and increased astrocyte proliferation. Taken together, these results indicate that Nef leads to down-modulation of GFAP expression and alteration of glutamate metabolism in astrocytes, and astrocyte proliferation and could be an important contributor to neuroHIV.
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Using Twitter Data Analysis to Understand the Perceptions, Awareness, and Barriers to the Wide Use of Pre-Exposure Prophylaxis in the United States.
User-generated social media posts such as tweets can provide insights about the publics perception, cognitive, and behavioral responses to health-related issues. Pre-Exposure Prophylaxis (PrEP) is one of the most effective ways to reduce the risk of HIV infection. However, its utilization is low in the US, especially among populations disproportionately affected by HIV such as the age group of under 24 years old. It is therefore important to understand the barriers to the wider use of PrEP in the US using social media posts. In this study, we collected tweets from Twitter about PrEP in the past 4 years to identify such barriers by first identifying tweets about personal discussions, and then performing textual analysis using word analysis, UMLS semantic type analysis, and topic modeling. We found that the public often discussed advocacy, risksbenefits, access, pricing, insurance coverage, legislation, stigma, health education, and prevention of HIV. This result is consistent with the literature and can help identify strategies for promoting the use of PrEP, especially among young adults.
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Epidemiology of herpes simplex virus type 2 in Europe systematic review, meta-analyses, and meta-regressions.
Herpes simplex virus type 2 (HSV-2) infection is a globally prevalent, life-long, sexually transmitted infection. This study characterized HSV-2 seroprevalence in Europe for various at-risk populations and proportions of HSV-2 detection in genital ulcer disease (GUD) and in genital herpes. Data on neonatal herpes and HSV-2s contribution to HIV transmission were also reviewed. Cochrane and PRISMA guidelines were followed to systematically review, synthesize, and report HSV-2 related findings. The search was conducted in PubMed and Embase databases up to February 20, 2022. Any publication reporting data on the outcome measures was included. Meta-analyses and meta-regressions were conducted. 211 relevant reports were identified, including 12 overall incidence measures, 294 overall (813 stratified by factors such as age and sex) seroprevalence measures, 13 overall (15 stratified by sex) proportions of HSV-2 detection in clinically diagnosed GUD, and 70 overall (183 stratified by factors such as age and sex) proportions of HSV-2 detection in laboratory-confirmed genital herpes. Pooled mean seroprevalence was 12.4% (95% CI 11.5-13.3%) among general populations, 27.8% (95% CI 17.5-39.4%) among men who have sex with men, 46.0% (95% CI 40.1-51.8%) among people living with HIV and people in HIV discordant couples, and 63.2% (95% CI 55.5-70.6%) among female sex workers. Most measures showed heterogeneity in HSV-2 seroprevalence. The pooled mean seroprevalence among general populations increased with age and was 0.65-fold (95% CI 0.58-0.74) lower in men than women. Seroprevalence decreased by 1% per calendar year. Pooled mean proportions of HSV-2 detection in GUD and in genital herpes were 22.0% (95% CI 15.3-29.6%) and 66.0% (95% CI 62.9-69.1%), respectively. HSV-2 detection in genital herpes cases was 1.21-fold (95% CI 1.10-1.32) higher in men compared to women and decreased by 1% per calendar year. Incidence of neonatal herpes indicated an increasing trend. Although seroprevalence is declining, a significant proportion of Europes population is infected with HSV-2. HSV-2 accounts for approximately one-fifth of GUD cases and two-thirds of genital herpes cases. Findings support the need to invest in HSV-2 vaccine development, and sexual and reproductive health services. Qatar National Research Fund NPRP 9-040-3-008 and pilot funding from the Biomedical Research Program at Weill Cornell Medicine in Qatar supported this study.
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A cross-sectional study on the prevalence of HIV and hepatitis B virus co-infection among students of a tertiary institution in Ekiti State, Southwest Nigeria.
Nigeria aims to eradicate public-health threats such as HIVAIDS and hepatitis B virus (HBV) by 2030. However, to achieve the short- and medium-term response target, and end the epidemic by 2030, there is the need to monitor and estimate the population level of HIV and HBV epidemic trends to boost the countrys strategic frameworks chances of success. Hence, we uncovered the prevalence of HIV and HBV among full-time, newly admitted undergraduate university students in Southwestern Nigeria between 2015 and 2017. In this regard, 4 ml of blood samples was collected from each subject into Ethylene Diamine Tetraacetic Acid (EDTA) bottles and were allowed to stand for one hour. Samples were allowed to separate into plasma and corpuscles on the bench. HIV screening was done using an immunochromatographic method via a highly sensitive kit DETERMINE® (Abbott Diagnostic Division, Netherlands) and were later confirmed using Enzyme Linked Immunosorbent Assay (ELISA) Uni-Gold® manufactured by Trinity Biotech Plc, Ireland. HBV screening was carried out using an immunoassay method for the detection of the hepatitis B surface antigen (HBsAg). Out of the 4,623 subjects recruited, 2,545 were male while 2,078 were female. The overall prevalence of HIV was found to be 0.13% while that of HBV was 2.23%. Conclusively, although HIV was found to be less prevalent among the study as compared to HBV however, the higher transmission propensity of HBV necessitates even more urgent efforts to eradicate the infectious diseases.
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Knowledge domain and emerging trends in HIV-MTB co-infection from 2017 to 2022 A scientometric analysis based on VOSviewer and CiteSpace.
Co-infection with
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Efficacy of a comprehensive strategy for the detection and treatment of hepatitis C infection in a population attending addiction centers.
The burden hepatitis C infection in people with history or current drug use suppose a high risk of hepatic complications and transmission infectious disease. This population is poor linked to heath system and is difficult to achieve them and support treatment because they have high rates of lost follow-up. Our aim was to evaluate an intervention for the diagnosis and treatment of chronic hepatitis C and HIV in this population. Six-hundred and eighty-three people attended in Drugs and Addictions Centers (DAC) were asked to participate in health counseling and provide blood sample for test HCV, HIV, and syphilis from April 2019 to June 2020. Totally 556 subjects were surveyed and tested. All of them were assigned to a patient navigation program to improve health education and linking to the sanitary system. Hepatitis C infection patients were evaluated in an ampliated medical consult to evaluate hepatic stage with transient liver elastography and initiated Direct Acting Antivirals to achieve Sustained Viral Response. Of the 556 patients who agreed to participate in the study, 33 (5.9%) had active HCV infection. Of the 33 patients infected with HCV, three were lost to follow-up once the diagnosis of HCV infection was made. Twenty-eight patients (93.3%) completed treatment and 26 achieved Sustained Viral Response (78.8%). Of the 30 patients, seven (23.3%) had advanced fibrosis, and of these, four (16.6%) had liver cirrhosis. One of the cirrhotic patients had hepatic space-occupying lesions at the baseline evaluation and was diagnosed with hepatocarcinoma. Our study suggests that the implementation of strategies based on personalized intervention models can contribute to the control of HCV infection in DAC users.
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null
We performed a systematic review of published cases. We describe 6 new cases of PCPCOVID-19 coinfection. Among our cases (n 6) and those in the literature (n 69) with available data, the median age (interquartile range IQR) was 59 (44-77) years (n 38), 72% (4765) were male, and the mortality rate was 30.9% (2168). Long-term corticosteroid use was noted in 45.1% (2351), advanced HIV infection (defined as a CD4 count <200 cellsμL) in 17.6% (951), and antineoplastic chemotherapy in 13.7% (751), consistent with known PCP risk factors. Notably, 56.7% (3847) had verifiable risk factors for PCP (high-dose corticosteroids, immunosuppressive therapy, and HIV infection) before COVID-19 infection. A median absolute lymphocyte count (IQR) of 0.61 (0.28-0.92) ×10 These findings suggest a need for greater attention to PCP risk factors among COVID-19 patients and consideration of PCP prophylaxis in these high-risk populations.
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Antibody Fc-chimerism and effector functions When IgG takes advantage of IgA.
Recent advances in the development of therapeutic antibodies (Abs) have greatly improved the treatment of otherwise drug-resistant cancers and autoimmune diseases. Antibody activities are mediated by both their Fab and the Fc. However, therapeutic Abs base their protective mechanisms on Fc-mediated effector functions resulting in the activation of innate immune cells by FcRs. Therefore, Fc-bioengineering has been widely used to maximise the efficacy and convenience of therapeutic antibodies. Today, IgG remains the only commercially available therapeutic Abs, at the expense of other isotypes. Indeed, production, sampling, analysis and related
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Persistence of spike-specific immune responses in BNT162b2-vaccinated donors and generation of rapid
The BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine. Here, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine. Overall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r0.863, P<0.0001) with neutralizing activity thus, providing a potential surrogate for neutralizing cell-based assays. The spike-specific T cell response was measured with a newly modified T-spot assay in which the high-homology peptide-sequences cross-reactive with other coronaviruses were removed. This response was induced in 46 participants after the first dose, and all six participants after the second dose, and remained detectable in 46 participants five months post-vaccination. We have also shown for the first time, that BNT162b2 vaccine enhanced T cell responses also against known human common viruses. In addition, we demonstrated the efficacy of a rapid ex-vivo T cell expansion protocol for spike-specific T cell expansion to be potentially used for adoptive-cell therapy in severe COVID-19, immunocompromised individuals, and other high-risk groups. There was a 9 to 13.7-fold increase in the number of expanded T cells with a significant increase of anti-spike specific response showing higher frequencies of both activation and cytotoxic markers. Interestingly, effector memory T cells were dominant in all four participants CD8 expanded memory T cells CD4 T cells were dominated by effector memory in 24 participants and by central memory in the remaining two participants. Moreover, we found that high frequencies of CD4 terminally differentiated memory T cells were associated with a greater reduction of spike-specific activated CD4 T cells. Finally, we showed that participants who had a CD4 central memory T cell dominance expressed a high CD69 activation marker in the CD4 activated T cells.
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Genome-wide association study of the age of onset of type 1 diabetes reveals HTATIP2 as a novel T cell regulator.
Type 1 diabetes, a disorder caused by autoimmune destruction of pancreatic insulin-producing cells, is more difficult to manage when it presents at a younger age. We sought to identify genetic correlates of the age of onset by conducting the first genome-wide association study (GWAS) treating the age of first diagnosis as a quantitative trait. We performed GWAS with a discovery cohort of 4,014 cases and a replication cohort of 493 independent cases. Genome-wide significant SNPs were mapped to a causal variant by Bayesian conditional analysis and gel shift assay. The causal protein-coding gene was identified and characterized by RNA interference treatment of primary human pan-CD4 T cells with RNA-seq of the transcriptome. The candidate gene was evaluated functionally in primary cells by CD69 staining and proliferation assays. Our GWAS replicated the known association of the age of diagnosis with the human leukocyte antigen complex (HLA-DQB1). The second signal identified was in an intron of the NELL1 gene on chromosome 11 and fine-mapped to variant rs10833518 (P < 1.54 × 10 This study implicates HTATIP2 as a new type 1 diabetes gene acting via T cell regulation. Larger population sample sizes are expected to reveal additional loci.
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Aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with HIV.
People living with HIV (PLWH) are at twice the risk of developing cardiovascular diseases and have more than four times higher odds of aortic aneurysm (AA) than the uninfected population. However, biomarkers of AA in PLWH are yet to be discovered. We aimed to investigate whether circulating biomarkers reflecting platelet activation, hemostasis and endothelial disruption, i.e. sCD40L, D-dimer, syndecan-1, and thrombomodulin, were associated with AA in PLWH. Five hundred seventy one PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study ≥40 years of age with an available contrast-enhanced CT scan as well as available biomarker analyses were included. The biomarkers were analyzed on thawed plasma. For each biomarker, we defined high level as a concentration in the upper quartile and low level as a concentration below the upper quartile. For D-dimer, the cut-off was defined as the lower limit of detection. Using unadjusted and adjusted logistic and linear regression models, we analyzed associations between AA and sCD40L, D-dimer, syndecan-1, and thrombomodulin, respectively in PLWH. PLWH had median (IQR) age 52 years (47-60), 88% were male, median (IQR) time since HIV diagnosis was 15 years (8-23), and 565 (99%) were currently on antiretroviral treatment. High level of sCD40L was associated with lower odds of AA in both unadjusted (odds ratio, OR, 0.23 (95% CI 0.07-0.77 SCD40L was associated with lower odds of AA whereas D-dimer was independently associated with higher odds of AA in PLWH. This calls for further investigations into specific biomarkers to aid early diagnosis of AA in PLWH.
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NELL1-Positive HIV-Associated Lupus-Like Membranous Nephropathy with Spontaneous Remission.
Kidney biopsy findings in patients with human immunodeficiency virus (HIV) are diverse, and optimal therapy for the various immune complex diseases in the setting of HIV is unknown. A man with well-controlled HIV developed nephrotic range proteinuria, and kidney biopsy revealed lupus-like glomerulonephritis with a predominantly membranous pattern of injury. He opted for conservative therapy and experienced spontaneous and sustained remission. Subsequent testing revealed neural epidermal growth factor-like 1 (NELL1)-positive glomerular immune deposits. NELL1-positive glomerular immune deposits were identified in a total of 2 of 5 tested HIV-associated membranous nephropathy (MN), which were morphologically dissimilar and one of which weakly co-expressed phospholipase A2 receptor (PLA2R). This case suggests potentially different outcomes in patients with immune complex diseases in the setting of HIV based on disease etiology and histopathology. HIV-associated MN is occasionally NELL1-positive.
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Case report Savolitinib induced severe adverse reactions resembling septic shock in an HIV-1-positive patient with advanced non-small cell lung cancer.
Savolitinib, a small-molecule inhibitor of the receptor tyrosine kinase mesenchymal-epithelial transition (MET) factor, was approved for the treatment of non-small cell lung cancer (NSCLC) by the China National Medical Products Administration in June 2021. Its safety for NSCLC treatment has been confirmed in several prospective cohort studies. Herein, we report a rare case of shock, a serious adverse event, after treatment with savolitinib in an HIV-1-positive patient with advanced NSCLC. A 38-year-old man with an 8-year history of HIV-1 positivity was diagnosed with NSCLC 5 years ago the lung cancer recurred after surgical resection. Despite chemotherapy, immunotherapy, and targeted therapy, tumor progression continued. He received savolitinib because of MET amplification. In the first 2 weeks of savolitinib use, he developed a mild rash on his trunk. In the following month, he was hospitalized for fever and circulatory shock thrice after taking savolitinib 400 mg. He had no urticaria or eosinophilia. During the three hospitalizations, he was negative for pathogens. His condition gradually improved after treatment with antibiotics, steroids, and vasopressors. Attention should be paid to the occurrence of septic shock-like presentations when using savolitinib in HIV-1 patients with NSCLC.
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Clofazimine for the treatment of tuberculosis.
Shorter (6-9 months), fully oral regimens containing new and repurposed drugs are now the first-choice option for the treatment of drug-resistant tuberculosis (DR-TB). Clofazimine, long used in the treatment of leprosy, is one such repurposed drug that has become a cornerstone of DR-TB treatment and ongoing trials are exploring novel, shorter clofazimine-containing regimens for drug-resistant as well as drug-susceptible tuberculosis. Clofazimines repurposing was informed by evidence of potent activity against DR-TB strains
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Missed opportunities for diagnosis of HIV in the emergency department using non-risk-based testing strategy.
The objective of this study was to identify the number of missed opportunities (MO) for human immunodeficiency virus (HIV) diagnoses within our emergency departments (EDs) and assess any significant associated patient characteristics. Following current Centers for Disease Control guidelines, an opt-out HIV screening program was implemented in 2 of 7 EDs within a large Southern healthcare system. This study sought to differentiate the risk of MO in opt-out compared to clinician-initiated, risk-based ED screening protocols. A retrospective analysis was conducted from August 2019 to March 2022 of adult patients (≥18 years old) screened for HIV, comparing the ED screening method and characterization of all MOs. MO was defined as any ED visit, before HIV seropositivity, that included sexually transmitted infection screening andor treatment with no HIV screening. Two EDs implemented generalized opt-out screening for all adult patients (>18 years old) whereas, the remaining 5 sites relied on clinician-initiated screening. Patient characteristics associated with an MO were evaluated by χ In total, 19,423 patients were screened for HIV, 142 of who tested positive. Of the 142 HIV-positive individuals, 12 (8.5%) had 1 MO and 3 of 12 (25%) had 2. The proportion of patients with a MO was significantly higher at clinician-initiated EDs as compared opt-out EDs (41.7% vs 13.9%, This novel study highlights the success and overall high positivity (0.7%) of an ED-based opt-out screening program. Taken together, the implementation of generalized opt-out screening within a large Southern healthcare system can rapidly increase overall screening, uncover a surprisingly high positivity rate, and decrease MOs for HIV diagnosis.
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Chemo-immunotherapy for metastatic non-squamous NSCLC in a patient with HIV infection A case report.
Activity and safety data of chemo-immunotherapy for patients with metastatic NSCLC and known HIV infection are still limited, since HIV-positive patients were generally excluded from clinical trials. Here we report the case of a metastatic NSCLC patient with HIV infection and undetectable viral load treated with first-line chemo-immunotherapy (pembrolizumab, carboplatin and pemetrexed), achieving a meaningful and durable objective response, with no treatment-related adverse events and no HIV-related complications. This report suggests that NSCLC patients with virologically controlled HIV infection can be safely treated with chemo-immunotherapy and should not be excluded from this treatment based on their viral infection only.
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Critical gaps in knowledge and implementation of recommendations by the US Preventive Services Task Force.
The United States Preventive Services Task Force (USPSTF) has issued 31 recommendations applicable to non-pregnant adults. We hypothesized variability in knowledge and implementation of these recommendations among US family medicine resident physicians. We performed two electronic surveys a local survey, and then a nationally-representative, multicenter, survey. We evaluated self-reported knowledge and implementation of USPSTF recommendations related to non-pregnant adults. 84 family medicine residents from 40 residency programs across 25 states participated. Knowledge and implementation of recommendations varied widely. Most residents lacked knowledge relating to breast cancer chemoprophylaxis (9.9 % known in detail or mostly know), BRCA-related genetic counseling (BRCA-GC) referral (30 %), tuberculosis (TB) screening (41 %), and sexually transmitted infection (STI) counseling (45 %). There is virtually no implementation of recommendations for breast cancer chemoprophylaxis (90 % neverrarely implement). Many residents neverrarely implement recommendations for BRCA-GC referral (75 %), TB screening (62 %), and HIV pre-exposure prophylaxis (61 %). This remained true even for residents in their final year of training. Relative to their male counterparts, female physicians more frequently implemented recommendations for BRCA-GC referral (11 % vs 0 % alwaysoften implement, p 0.019), cervical cancer screening (100 % vs 83 %, p 0.019), and folic acid supplementation (60 % vs 29 %, p 0.007). Knowledge and implementation of recommendations were strongly related (β 0.75, 95 % CI 0.50-1.00, p < 0.001, Spearman R Critical gaps exist in resident knowledge and implementation of USPSTF recommendations. We discuss urgent implications for cancer prevention, public health, and health equity.
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Adverse perinatal outcomes associated with antiretroviral therapy in women living with HIV A systematic review and meta-analysis.
Maternal HIV infection is associated with an increased risk of adverse perinatal outcomes. The World Health Organization (WHO) recommends immediate initiation of lifelong antiretroviral therapy (ART) for all people living with HIV, including pregnant women living with HIV (WLHIV). We aimed to assess the risk of adverse perinatal outcomes in WLHIV receiving ART compared to ART-naïve WLHIV and HIV-negative women. We conducted a systematic literature review by searching PubMed, CINAHL, Global Health, and EMBASE for studies published between Jan 1, 1980, and April 20, 2020. Two investigators independently selected relevant studies and extracted data from studies reporting on the association of pregnant WLHIV receiving ART with adverse perinatal outcomes. Perinatal outcomes examined were preterm birth (PTB), very PTB, spontaneous PTB (sPTB), low birth weight (LBW), very LBW (VLBW), term LBW, preterm LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth, and neonatal death. Random-effects meta-analyses examined the risk of adverse perinatal outcomes in WLHIV receiving ART compared to ART-naïve WLHIV and HIV-negative women. Subgroup and sensitivity analyses were performed based on country income status and study quality, and adjustment for confounding factors assessed. Of 94,594 studies identified, 73 cohort studies, including 424,277 pregnant women, met the inclusion criteria. We found that WLHIV receiving ART are associated with a significantly decreased risk of PTB (relative risk 0.79, 95% CI 0.67-0.93), sPTB (0.46, 0.32-0.66), LBW (0.86, 0.79-0.93), and VLBW (0.62, 0.39-0.97) compared to ART-naïve WLHIV. However, WLHIV receiving ART are associated with a significantly increased risk of PTB (1.42, 1.28-1.57), sPTB (2.20, 1.32-3.67), LBW (1.58, 1.36-1.84), term LBW (1.88, 1.23-2.85), SGA (1.69, 1.32-2.17), and VSGA (1.22, 1.10-1.34) compared to HIV-negative women. ART reduces the risk of adverse perinatal outcomes in pregnant WLHIV, but the risk remains higher than in HIV-negative women. Our findings support the WHO recommendation of immediate initiation of lifelong ART for all people living with HIV, including pregnant WLHIV. httpswww.crd.york.ac.ukprospero, identifier CRD42021248987.
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HIV-Associated Nephropathy in 2022.
HIV-associated nephropathy (HIVAN) is a renal parenchymal disease that occurs exclusively in people living with HIV. It is a serious kidney condition that may possibly lead to end-stage kidney disease, particularly in the HIV-1 seropositive patients. The African-American population has increased susceptibility to this comorbidity due to a strong association found in the This study reviews the current understanding of HIVAN including its epidemiology, mechanism of disease, related genetic factors, clinical profile, and pathophysiologic effects of management options for patients.
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Change in body weight and risk of hypertension after switching from efavirenz to dolutegravir in adults living with HIV evidence from routine care in Johannesburg, South Africa.
The integrase strand transfer inhibitor (INSTI) dolutegravir is recommended in World Health Organization guidelines, but is associated with weight gain. We evaluated weight change in patients switching from efavirenz to dolutegravir in first-line antiretroviral therapy (ART) in Johannesburg, South Africa. We conducted a prospective cohort study of adults (≥16 years) of black African ancestry with HIV who initiated ART between January 2010-December 2020. Patients were propensity score-matched 11 (unexposed i.e. remaining on efavirenz exposed i.e. switched from efavirenz to dolutegravir) on sex, age, months on ART, first ART regimen, haemoglobin, body mass index (BMI), blood pressure, viral load and CD4 count. We used linear regression to assess the effect of switching from efavirenz to dolutegravir on weight change and hypertension 12 months after exposure. We matched 794 patients switching to dolutegravir to 794 remaining on efavirenz. Exposed patients had a higher mean change in weight (1.78 kg 95% confidence interval (CI)1.04,2.52 kg) from start of follow-up to 12 months vs. unexposed. We also found a 14.2 percentage point increase (95% CI 10.6,17.7) in the risk of hypertension in those exposed to dolutegravir vs those that remained on efavirenz. In a real-world population, patients gained more weight and were at higher risk of hypertension after switching from efavirenz to dolutegravir than those remaining on efavirenz. Longer follow-up is needed, however, to determine if INSTI-associated weight gain is associated with changes in non-communicable disease risk over the long-term, or whether weight gain is sustained, as seen in clinical trials. This study has been made possible by the generous support of the American People and the Presidents Emergency Plan for AIDS Relief (PEPFAR) through the United States Agency for International Development (USAID), under the terms of cooperative agreement cooperative Agreement 72067419CA00004. In addition to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 1K01MH105320-01A1.
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Characterization of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Conformational States on Infectious Virus Particles.
Human immunodeficiency virus (HIV-1) entry into cells involves triggering of the viral envelope glycoprotein (Env) trimer (gp120gp41
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The HIV paradox perinatal mortality is lower in HIV-positive mothers. A field case-control study in Ethiopia.
Sub-Saharan African countries have the highest perinatal mortality rates. Although HIV is certainly a risk factor for perinatal death, ART programmes have been associated with better outcomes. We aimed to investigate how maternal HIV affects perinatal mortality. We carried out a nested case-control study at the Saint Luke Hospital, Wolisso, Ethiopia. Data on sociodemographic characteristics current maternal conditions past obstetric history ANC services utilisation were collected. The association between perinatal mortality and HIV was assessed with a logistic regression adjusting for potential confounders. A total of 3,525 birthing women were enrolled, including 1,175 cases and 2,350 controls. Perinatal mortality was lower among HIV-positive women (18.3% vs 33.6% p0.007). The crude analysis showed a protective effect of HIV (OR0.442 95%CI0.241-0.810) which remained after adjustment (aOR0.483 95%CI0.246-0.947). Amongst HIV-negative women, access to ANC for women from rural areas was almost half (18.8% vs. 36.2% p<0.001), whereas in HIV-positive women no differences were noted (p0.795). Among HIV-positive mothers, perinatal mortality was halved and differences in access to ANC services by area were eliminated. These data highlight the benefits of integrating ANC and HIV services in promoting access to the health care system, reducing inequalities and improving neonatal mortality.
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Epidemiology of herpes simplex virus type 2 in the Middle East and North Africa Systematic review, meta-analyses, and meta-regressions.
Herpes simplex virus type 2 (HSV-2) infection is a prevalent, sexually transmitted infection with poorly characterized prevalence in the Middle East and North Africa (MENA) region. This study characterized HSV-2 epidemiology in MENA. The systematic review was guided by the Cochrane Collaboration Handbook and findings were reported following PRISMA guidelines. Random-effects meta-analyses and meta-regressions were performed to estimate pooled mean outcome measures and to assess predictors of HSV-2 antibody prevalence (seroprevalence), trends in seroprevalence, and between-study heterogeneity. 61 overall (133 stratified) HSV-2 seroprevalence measures and two overall (4 stratified) proportion measures of HSV-2 detection in laboratory-confirmed genital herpes were extracted from 37 relevant publications. Pooled mean seroprevalence was 5.1% (95% CI 3.6-6.8%) among general populations, 13.3% (95% CI 8.6-18.7%) among intermediate-risk populations, 20.6% (95% CI 5.3-42.3%) among female sex workers, and 18.3% (95% CI 3.9-39.4%) among male sex workers. Compared to Fertile Crescent countries, seroprevalence was 3.39-fold (95% CI 1.86-6.20) and 3.90-fold (95% CI 1.78-8.57) higher in Maghreb and Horn of Africa countries, respectively. Compared to studies published before 2010, seroprevalence was 1.73-fold (95% CI 1.00-2.99) higher in studies published after 2015. Pooled mean proportion of HSV-2 detection in genital herpes was 73.8% (95% CI 42.2-95.9%). MENA has a lower HSV-2 seroprevalence than other world regions. Yet, 1 in 20 adults is chronically infected, despite conservative prevailing sexual norms. Seroprevalence may also be increasing, unlike other world regions. Findings support the need for expansion of surveillance and monitoring of HSV-2 infection in MENA. This article is protected by copyright. All rights reserved.
36,815,406
Radioimmunotherapy for the treatment of infectious diseases a comprehensive update.
Corona Virus Disease of 2019 (COVID-19) pandemic has renewed interest in monoclonal antibodies for treating infectious diseases. During last two decades experimental data has been accumulated showing the potential of radioimmunotherapy (RIT) of infectious diseases. In addition, COVID-19 pandemic has created a novel landscape for opportunistic fungal infections in post-COVID-19 patients resulting from severe immune suppression. We analyze recent results on targeting pan-antigens shared by fungal pathogens in mouse models and in healthy dogs on developing RIT of prosthetic joint infections (PJI) examine RIT as potential human immunodeficiency virus (HIV) cure strategy and analyze its mechanisms and safety. Literature review was performed using PubMed and Google Scholar and includes relevant articles from 2000 to 2022. Some of the RIT of infection applications can, hopefully, be moved into the clinic earlier than others after pre-clinical development 1) RIT of opportunistic fungal infections might contribute to saving lives as current anti-fungal drugs do not work in severely immunocompromised patients 2) RIT of patients with PJI. Success of RIT in these patients will allow to expand the application of RIT to other similarly vulnerable patients populations such as cancer patients with weakened immune system and organ transplant recipients.
36,815,334
The testing imperative Why the US EHE needs to renew efforts to expand HIV testing in clinical and community-based settings.
Data from several modeling studies demonstrate that large-scale increases in HIV testing across settings with a high burden of HIV may produce the largest incidence reductions to support the US Ending the HIV Epidemic (EHE) initiatives goal of reducing new HIV infections 90% by 2030. Despite US Centers for Disease Control and Preventions recommendations for routine HIV screening within clinical settings and at least yearly screening for individuals most at risk of acquiring HIV, fewer than half of US adults report ever receiving an HIV test. Furthermore, total domestic funding for HIV prevention has remained unchanged between 2013 to 2019. The authors describe the evidence supporting the value of expanded HIV testing, identify challenges in implementation and present recommendations to address these barriers through approaches at local and federal levels to reach EHE targets.
36,815,177
Neuromeningeal cryptococcosis in an HIV-negative patient with pulmonary tuberculosis in the Infectious and tropical diseases department of the University teaching hospital Point G of Bamako, Mali.
Neuromeningeal cryptococcosis and pulmonary tuberculosis are respectively serious mycotic and bacterial infections occurring in a subject regardless of its HIV serological status. We report here a case of neuromeningeal cryptococcosis associated with pulmonary tuberculosis and malnutrition in an HIV-seronegative patient with a CD4 count of 750mm La cryptococcose neuroméningée et la tuberculose pulmonaire sont respectivement des infections mycosique et bactérienne graves survenant chez un sujet quel que soit son statut sérologique au VIH. Nous rapportons ici un cas de cryptococcose neuroméningée associée à une tuberculose pulmonaire et une dénutrition chez une patiente séronégative pour le VIH ayant un taux de CD4 à 750mm
36,815,061
Perceptions of stigma among pulmonary tuberculosis patients in Thailand, and the links to delays in accessing healthcare.
Delay in seeking care increases the morbidity and mortality in tuberculosis (TB) patients and leads to increased likelihood of transmission within the community. Stigmatisation is one of the influencing factors causing delay in accessing healthcare when experiencing symptoms of TB. This study aimed to explore the relationship between TB stigmatisation and patient delay among pulmonary tuberculosis (PTB) patients. A mixed methods study was undertaken among 300 randomly sampled participants who completed questionnaire surveys, supplemented by 25 in-depth interviews with purposively-sampled participants identified as delaying access to healthcare. Participants reporting higher perceived levels of TB stigmatisation demonstrated a longer duration of patient delay ( The study highlights that accurate and objective information about TB is required to reduce societal stigmatisation related to the disease, thereby reducing the reluctance of patients to access healthcare.
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