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36,803,328
Indigenous gender and wellness a scoping review of Canadian research.
This scoping review examined research publications related to health andor wellness along with gender among Canadian Indigenous populations. The intent was to explore the range of articles on this topic and to identify methods for improving gender-related health and wellness research among Indigenous peoples. Six research databases were searched up to 1 February 2021. The final selection of 155 publications represented empirical research conducted in Canada, included Indigenous populations, investigated health andor wellness topics and focused on gender. Among the diverse range of health and wellness topics, most publications focused on physical health issues, primarily regarding perinatal care and HIV- and HPV-related issues. Gender diverse people were seldom included in the reviewed publications. Sex and gender were typically used interchangeably. Most authors recommended that Indigenous knowledge and culture be integrated into health programmes and further research. More health research with Indigenous peoples must be conducted in ways that discern sex from gender, uplift the strengths of Indigenous peoples and communities, privilege community perspectives, and attend to gender diversity using methods that avoid replicating colonialism, promote action, change stories of deficit, and build on what we already know about gender as a critical social determinant of health.
36,803,322
Selection of cognitive impairment screening tools for longitudinal implementation in an HIV clinical care setting.
To address and slow the increasing burden of cognitive impairment in people surviving to older ages with HIV requires longitudinal monitoring of cognition. We conducted a structured literature review to identify peer-reviewed studies employing validated cognitive impairment screening tools in adult populations of people with HIV. We identified three key criteria for selection and ranking of a tool (a) strength of validity of the tool (b) acceptability and feasibility of the tool (c) ownership of the data from the assessment. From our structured review of 105, 29 studies met our inclusion criteria, within which 10 cognitive impairment screening measurement tools were validated in a population of people with HIV. The BRACE, NeuroScreen and NCAD tools were ranked highly when compared with the other seven tools. Additionally, patient population and clinical setting characteristics (such as availability of quiet space, timing of assessment, security of electronic resources, and ease of linkage to electronic health records) were included in our framework for selection of tools. Numerous validated cognitive impairment screening tools are available to monitor for cognitive changes in the HIV clinical care setting, detecting opportunities for earlier intervention to reduce cognitive decline and preserve quality of life.
36,803,272
Behaviors associated with HIV transmission risk among rural sexual and gender minority and majority residents.
Multiple rural states and communities experience elevated rates of human immunodeficiency virus (HIV), often associated with diminished healthcare access and increased drug use. Though a substantial proportion of rural populations are sexual and gender minorities (SGM), little is known of this group regarding substance use, healthcare utilization, and HIV transmission behaviors. During May-July 2021, we surveyed 398 individuals across 22 rural Illinois counties. Participants included cisgender heterosexual males (CHm) and females (CHf) (
36,803,199
The Fight is Two Times as Hard A Qualitative Examination of a Violence Syndemic Among Young Black Sexual Minority Men.
Young Black men who have sex with men (YBMSM) are disproportionately impacted by violence, including violence rooted in anti-Black racism, sexual identity bullying, and neighborhood violence rooted in structural racism and inequities. These multiple forms of violence are frequently co-occurring and interactive creating syndemic conditions that can negatively impact HIV care. This qualitative study is based on in-depth interviews with 31 YBMSM, aged 16-30 years, living with HIV in Chicago, IL, to examine how violence has impacted their lives. Using thematic analysis, we identified five themes that reflect how YBMSM experience violence at the intersection of racism, homonegativity, socioeconomic status, and HIV status (a) the experience of intersectional violence (b) long histories of violence contributed to hypervigilance, lack of safety, and lack of trust (c) making meaning of violence and the importance of strength (d) normalizing violence for survival and (e) the cyclical nature of violence. Our study highlights how multiple forms of violence can accumulate across an individuals life and contribute to social and contextual situations that further contribute to violence and negatively impact mental health and HIV care.
36,803,177
Tracing the recent updates on vaccination approaches and significant adjuvants being developed against HIV.
Human Immunodeficiency Virus type 1 (HIV-1) the causative agent of Acquired Immunodeficiency Syndrome (AIDS), has been a major target of the scientific community to develop a medication or vaccine for its cure and prevention. Some successful discoveries have been made during the last two decades in the form of availability of anti-viral therapy in endemic regions. Nevertheless, a total cure and safety vaccine has not yet been designed to eradicate HIV from the world. The purpose of this comprehensive study is to compile widespread recent data regarding therapeutic interventions against HIV and to determine future research needs in this field. A systematic research strategy has been used to gather data from recent, most advanced published electronic sources. Literature-based results show that experiments at the in-vitro level and animal models are continuously in research annals and are providing some positive results to be used in human models. Some potential vaccine and drug adjuvants have been introduced in recent years through rigorous scientific efforts. However, there is still a gap and more work is needed in the direction of modern drug and vaccination designs. Moreover coordination is necessary among researchers, educationists, public health workers, social workers and the general community to communicate and coordinate the repercussions associated with the deadly disease. It is important for taking timely measures regarding mitigation and adaptation with HIV in future.
36,803,172
Addressing the unmet mental health needs of people living with HIV a scoping review of interventions in sub-Saharan Africa.
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36,803,171
Opportunities to leverage reproductive goals and ideals among South African men to promote HIV testing, treatment and prevention A qualitative study.
Despite significant gains in HIV testing, treatment and prevention in sub-Saharan Africa, male engagement and retention in HIV care remains a challenge. We conducted in-depth interviews with 25 men with HIV (MWH) living in rural South Africa to explore how mens reproductive goals could inform approaches to engage men and their female partners in HIV care and prevention. Themes were organised into opportunities and barriers for HIV care, treatment and prevention that men articulated as important to their reproductive goals at the individual, couple and community levels. At the individual level, men are motivated to remain healthy so they can raise a healthy child. At the couple level, the importance of maintaining a healthy partner to raise children may promote serostatus-disclosure, testing and encourage men to support partners to access HIV prevention. At the community level, men described the need to be seen as fathers who provide for their families as important motivators to engage in care. Men also articulated barriers including low knowledge about antiretroviral-based HIV prevention, lack of trust within partnerships and community stigma. Addressing reproductive goals of MWH may be an untapped path for promoting male engagement in HIV care and prevention for their partners.
36,803,094
I cant remember the last time I was comfortable about being home lived experience perspectives on thriving following homelessness.
Strategies for preventing and ending homelessness are frequently measured by their effectiveness on indices of tenancy sustainment. To shift this narrative, we conducted research to identify what is needed to thrive following homelessness from the perspectives of persons with lived experience in Ontario, Canada. Conducted in the context of a community-based participatory research study aimed at informing the development of intervention strategies, we interviewed 46 persons living with mental illness andor substance use disorder Participants described experiences of living in a state of lack following homelessness. This essence was expressed through four themes 1) housing as part one of the journey to home 2) finding and keeping my people 3) meaningful activity as critical for thriving following homelessness and 4) struggling to access mental health supports in the context of challenging circumstances. Individuals struggle to thrive following homelessness in the context of insufficient resources. There is a need to build on existing interventions to address outcomes beyond tenancy sustainment.
36,803,053
Barriers, opportunities, and potential costs of expanding HIV support services.
Experiencing housing instability, food insecurity, and financial stress can negatively impact retention in care and treatment adherence for people living with HIV. Expanding services that support socioeconomic needs could help improve HIV outcomes. Our objective was to investigate barriers, opportunities, and costs of expanding socioeconomic support programs. Semi-structured interviews were conducted with organizations serving U.S. Ryan White HIVAIDS Program clients. Costs were estimated from interviews, organization documents, and city-specific wages. Organizations reported complex patient, organization, program, and system challenges as well as several opportunities for expansion. The average one-year per-person cost for engaging new clients was $196 for transportation, $612 for financial aid, $650 for food aid, and $2498 for short-term housing (2020 USD). Understanding potential expansion costs is important for funders and local stakeholders. This study provides a sense of magnitude for costs to scale-up programs to better meet socioeconomic needs of low-income patients living with HIV.
36,802,932
Favorable Impact of Community Adherence Support Groups on Retention in Care and Viral Suppression Rates among Persons with HIV Receiving Antiretroviral Therapy in Mozambique.
Community adherence support groups (CASG) was one of the first differentiated service delivery (DSD) models introduced in Mozambique. This study assessed the impact of this model on retention in care, loss-to-follow-up, and viral suppression among antiretroviral therapy-treated adults in Mozambique. A retrospective cohort study included CASG-eligible adults enrolled between April 2012 and October 2017 at 123 health facilities in Zambézia province. Propensity-score matchings (11 ratio) were used to allocate CASG members and those who never enrolled in a CASG. Logistic regressions were performed to estimate the impact of CASG membership on 6- and 12-month retention and viral load suppression. Cox proportional regression was used to model differences in loss to follow-up (LTFU). Data from 26,858 patients were included. The median age at CASG eligibility was 32 years, 75% were female, with 84% residing in rural areas. A total of 93% and 90% of CASG members were retained in care at 6 and 12 months, respectively, while 77% and 66% non-CASG members were retained during the same periods. The odds of being retained in care at 6- and 12-months were significantly higher among patients receiving antiretroviral therapy via CASG support (aOR 4.19 95% CI 3.79-4.63, p<0.001, and aOR 4.43 95% CI 4.01-4.90, p<0.001, respectively). Among 7,674 patients with available viral load measurements, the odds of being virally suppressed was higher among CASG members (aOR 1.14 95% CI 1.02-1.28, p<0.001. Non-CASG members had a significantly higher likelihood of being LTFU (aHR 3.45 95% CI 3.20-3.73, p<0.001).While Mozambique rapidly scales up multi-month drug dispensation as the preferred DSD model, this study emphasizes the continued importance of CASG as an efficacious DSD alternative, especially among patients residing in rural areas, where CASG acceptability is higher.
36,802,921
Efficacy, safety and tolerability of Biktarvy in HIV-1 infection A scoping review.
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36,802,827
Relapsing donovanosis rhyming with unexplained decline in CD4 count in a person living with HIVAIDS Long-term follow up and therapeutic outcome.
Donovanosis is a chronic genital ulcerative disease caused by the intracellular Gram-negative bacterium Klebsiella granulomatis, reported more frequently in people living with HIVAIDS (PLHA). Here we present a case of relapsing donovanosis in a PLHA on second line antiretroviral therapy who had episodes of transient unexplained decrease in CD4 counts associated with rapid growth of the lesion and non-responsiveness to treatment followed by clinical resolution coinciding with recovery of the CD4 count.
36,802,408
Fertility trends by HIV status in a health and demographic surveillance study in Magu District, Tanzania, 1994-2018.
Sub-Saharan Africa (SSA) has the highest fertility rates and highest HIV disease burden globally. However, it is not clear how the rapid expansion of anti-retroviral therapy (ART) for HIV has impacted the fertility gap between HIV-infected and uninfected women. We used data from a Health and Demographic Surveillance System (HDSS) in north-western Tanzania to explore trends in fertility rates and the relationship between HIV and fertility over the 25-year period. From 1994 to 2018, births and population denominators from the HDSS population were used to obtain age-specific fertility rates (ASFRs) and total fertility rates (TFRs). HIV status was extracted from eight rounds of epidemiologic serological surveillances (1994-2017). Fertility rates by HIV status and in different levels of ART availability were compared over time. Independent risk factors for fertility changes were examined using Cox proportional hazard models. There were 24,662 births from 36,814 women (15-49) who contributed a total of 145,452.5 Person-Years of follow-ups. The TFR declined from 6.5 births per woman in 1994-1998 to 4.3 births per woman in 2014-2018. The number of births per woman was 40% lower in women living with HIV than in HIV-uninfected women (4.4 vs. 6.7), although this difference narrowed over time. The fertility rate in HIV-uninfected women was 36% lower in 2013-2018 than in 1994-1998(age-adjusted HR 0.641 95% CI 0.613-0.673). In contrast, the fertility rate in women living with HIV was relatively unchanged over the same follow up period (age-adjusted HR 1.099 95% CI 0.870-1.387). There was a notable fertility decline among women in the study area from 1994 to 2018. Fertility remained lower in women living with HIV than in HIV-uninfected women, but the difference continued to narrow over time. These results highlight the need for more research into fertility changes, fertility desire and family planning use in Tanzanian rural communities.
36,802,388
Assessment of HIV viral load monitoring in remote settings in Vietnam - comparing people who inject drugs to the other patients.
Increasing access to viral load (VL) monitoring is essential to fight HIV epidemics. In remote settings in Vietnam, using dried blood spot (DBS) sampling for specimen collection could improve the situation. Here, people who inject drugs (PWID) represent many newly antiretroviral therapy (ART)-initiated patients. The goals of this evaluation were to evaluate if access to VL monitoring and the rate of virological failure differed between PWID and non-PWID. Prospective cohort study of patients newly initiated on ART in remote settings in Vietnam. DBS coverage at 6, 12 and 24 months of ART was investigated. Factors associated with DBS coverage were identified through logistic regression, as were factors associated with virological failure (VL ≥1,000 copiesmL) at 6, 12 and 24 months of ART. Overall 578 patients were enrolled in the cohort, of whom 261 (45%) were PWID. DBS coverage improved from 74.7% to 82.9% between 6 and 24 months of ART (p 0.001). PWID status was not associated with DBS coverage (p 0.74), but DBS coverage was lower in patients who were late to clinical visits and in those in WHO stage 4 (p 0.023 and p 0.001, respectively). The virological failure rate decreased from 15.8% to 6.6% between 6 and 24 months of ART (p<0.001). In multivariate analysis, PWID were more at risk of failure (p 0.001), as were patients who were late to clinical visits (p<0.001) and not fully adherent (p<0.001). Despite training and simple procedures, DBS coverage was not perfect. DBS coverage was not associated with PWID status. Close management is required for effective routine HIV VL monitoring. PWID were more at risk of failure, as were patients who were not fully adherent and patients who were late to clinical visits. Specific interventions targeting these patients are needed to improve their outcomes. Overall, efforts in coordination and communication are essential to improve global HIV care. Clinical Trial Number NCT03249493.
36,802,206
HIV-Related Stigma, Social Support, and Symptoms of Mental Health Disorders Among People with HIV Initiating HIV Care in Cameroon.
HIV-related stigma has been associated with poor mental health among people with HIV (PWH). Social support is a potentially modifiable factor that may buffer negative mental health sequelae of HIV-related stigma. Little is known about the extent to which the modifying effect of social support differs across mental health disorders. Interviews were conducted with 426 PWH in Cameroon. Log binomial regression analyses were used to estimate the association between high anticipated HIV-related stigma and low social support from family or friends and symptoms of depression, anxiety, post-traumatic stress disorder (PTSD), and harmful alcohol use, separately. Anticipated HIV-related stigma was commonly endorsed with ∼80% endorsing at least 1 of 12 stigma-related concerns. In multivariable analyses, high anticipated HIV-related stigma was associated with greater prevalence of symptoms of depression adjusted prevalence ratio (aPR) 1.6 (95% confidence interval CI 1.1-2.2) and anxiety aPR 2.0 (95% CI 1.4-2.9). Low social support was associated with greater prevalence of symptoms of depression aPR 1.5 (95% CI 1.1-2.2), anxiety aPR 1.7 (95% CI 1.2-2.5), and PTSD aPR 1.6 (95% CI 1.0-2.4). However, social support did not meaningfully modify the relationship between HIV-related stigma and symptoms of any mental health disorders explored. Anticipated HIV-related stigma was commonly reported among this group of PWH initiating HIV care in Cameroon. Social concerns related to gossip or losing friends were of the greatest concern. Interventions focused on reducing stigma and strengthening support systems may be particularly beneficial and have the potential to improve the mental health of PWH in Cameroon.
36,802,000
The interplay among HIV, monocytesmacrophages, and extracellular vesicles a systematic review.
Despite effective antiretroviral therapies, chronic inflammation and spontaneous viral blips occur in HIV-infected patients. Given the roles for monocytesmacrophages in HIV pathogenesis and extracellular vesicles in intercellular communication, we performed this systematic review to delineate the triad of HIV, monocytesmacrophages, and extracellular vesicles in the modulation of immune activation and HIV activities. We searched PubMed, Web of Science, and EBSCO databases for published articles, up to 18 August 2022, relevant to this triad. The search identified 11,836 publications, and 36 studies were deemed eligible and included in this systematic review. Data were extracted for the characteristics of HIV, monocytesmacrophages, and extracellular vesicles used for experiments and the immunologic and virologic outcomes in extracellular vesicle recipient cells. Evidence for the effects on outcomes was synthesized by stratifying the characteristics by outcomes. In this triad, monocytesmacrophages were potential producers and recipients of extracellular vesicles, whose cargo repertoires and functionalities were regulated by HIV infection and cellular stimulation. Extracellular vesicles derived from HIV-infected monocytesmacrophages or the biofluid of HIV-infected patients enhanced innate immune activation and HIV dissemination, cellular entry, replication, and latency reactivation in bystander or infected target cells. These extracellular vesicles could be synthesized in the presence of antiretroviral agents and elicit pathogenic effects in a wide range of nontarget cells. At least eight functional types of extracellular vesicles could be classified based on the diverse extracellular vesicle effects, which were linked to specific virus- andor host-derived cargos. Thus, the monocytemacrophage-centered multidirectional crosstalk through extracellular vesicles may help sustain persistent immune activation and residual viral activities during suppressed HIV infection.
36,801,775
Successful implementation of new Swiss recommendations on breastfeeding of infants born to women living with HIV.
Swiss national recommendations advise, since end of 2018, supporting women with HIV who wish to breastfeed. Our objective is to describe the motivational factors and the outcome of these women and of their infants. mothers included in MoCHiV with a delivery between January 2019 and February 2021 who fulfilled the criteria of the optimal scenario (adherence to cART, regular clinical care, and suppressed HIV plasma viral load (pVL) of <50 RNA copiesml) and who decided to breastfeed after a shared decision-making process, were approached to participate in this nested study and asked to fill-in a questionnaire exploring the main motivating factors for breastfeeding. Between January 9, 2019 and February 7, 2021, 41 women gave birth, and 25 decided to breastfeed of which 20 accepted to participate in the nested study. The three main motivational factors of these women were bonding, neonatal and maternal health benefits. They breastfed for a median duration of 6.3 months (range 0.7-25.7, IQR 2.5-11.1). None of the breastfed neonates received HIV post-exposure prophylaxis. There was no HIV transmission 24 infants tested negative for HIV at least 3 months after weaning one mother was still breastfeeding when we analyzed the data. As a result of a shared decision-making process, a high proportion of mothers expressed a desire to breastfeed. No breastfed infant acquired HIV. The surveillance of breastfeeding mother-infant pairs in high resource settings should be continued to help update guidelines and recommendations.
36,801,622
Cancers attributable to infectious agents in Italy.
To provide an evidence-based, comprehensive assessment of the current burden of infection-related cancers in Italy. We calculated the proportion of cancers attributable to infectious agents (Helicobacter pylori Hp hepatitis B virus HBV and hepatitis C virus HCV human papillomavirus HPV human herpesvirus-8 HHV8 Epstein-Barr virus EBV and human immunodeficiency virus HIV) to estimate the burden of infection-related cancer incidence (2020) and mortality (2017). Data on the prevalence of infections were derived from cross-sectional surveys of the Italian population, and relative risks from meta-analyses and large-scale studies. Attributable fractions were calculated based on the counterfactual scenario of a lack of infection. We estimated that 7.6% of total cancer deaths in 2017 were attributable to infections, with a higher proportion in men (8.1%) than in women (6.9%). The corresponding figures for incident cases were 6.5%, 6.9% and 6.1%. Hp was the first cause of infection-related cancer deaths (3.3% of the total), followed by HCV (1.8%), HIV (1.1%), HBV (0.9%), HPV, EBV and HHV8 (each ≤0.7%). Regarding incidence, 2.4% of the new cancer cases were due to Hp, 1.3% due to HCV, 1.2% due to HIV, 1.0% due to HPV, 0.6% due to HBV and <0.5% due to EBV and HHV8. Our estimate of 7.6% of cancer deaths and 6.9% of incident cases that were attributable to infections in Italy is higher than those estimated in other developed countries. Hp is the major cause of infection-related cancer in Italy. Prevention, screening and treatment policies are needed to control these cancers, which are largely avoidable.
36,801,593
Population-level impact of beliefs and attitudes on vaccine decision-making in South Africa results from the COVID-19 Vaccine Survey (20212022).
In addition to being home to more than seven million HIV-infected individuals, South Africa also has a high burden of COVID-19 and related comorbidities worldwide. We aimed to identify the most influential beliefs and attitudes on vaccine decision-making behavior. This study used panel data from cross-sectional surveys. We used the data from Black South Africans who participated in the COVID-19 Vaccine Surveys (November 2021 and FebruaryMarch 2022) in South Africa. Besides standard risk factor analysis, such as multivariable logistic regression models, we also used the modified version of population attributable risk percent and estimated the population-level impacts of beliefs and attitudes on vaccine decision-making behavior using the methodology in multifactorial setting. A total of 1399 people (57% men and 43% women) who participated in both surveys were analyzed. Of these, 336 (24%) reported being vaccinated in survey 2. Overall low perceived risk, concerns around efficacy, and safety were identified as the most influential factors and associated with 52%-72% (<40 years) and 34%-55% (40 years) of the unvaccinated individuals. Our findings highlighted the most influential beliefs and attitudes on vaccine decision-making and their population-level impacts, which are likely to have significant public health implications exclusively for this population.
36,801,347
The association of epicardial adipose tissue volume and density with coronary calcium in HIV-positive and HIV-negative patients.
We sought to assess and compare the association of epicardial adipose tissue (EAT) with cardiovascular disease (CVD) in HIV-positive and HIV-negative groups METHODS AND RESULTS Using existing clinical databases we analysed 700 patients (195 HIV-positive, 505 HIV-negative). CVD was quantified by the presence of coronary calcification from both dedicated cardiac computed tomography (CT) and non-dedicated CT of the thorax. Epicardial adipose tissue (EAT) was quantified using dedicated software. The HIV-positive group had lower mean age (49.2 versus 57.8, p<0.005), higher proportion of male sex (75.9% versus 48.1%, p<0.005) and lower rates of coronary calcification (29.2% versus 58.2%, p<0.005). Mean EAT volume was also lower in the HIV-positive group (68mm3 versus 118.3mm3, p<0.005). Multiple linear regression demonstrated EAT volume was associated hepatosteatosis (HS) in the HIV-positive group but no the HIV-negative group after adjustment for BMI (p<0.005 versus p0.066). In the multivariate analysis, after adjustment for CVD risk factors, age, sex, statin use and body mass index (BMI), EAT volume and hepatosteatosis were significantly associated with coronary calcification (odds ratio OR 1.14, p<0.005 and OR 3.17, p<0.005 respectively). In the HIV-negative group the only significant association with EAT volume after adjustment was total cholesterol (OR 0.75, p0.012). We demonstrated a strong and significant independent association of EAT volume and coronary calcium, after adjustment, in HIV-positive group but not in the HIV-negative group. This result hints at differences in the mechanistic drivers of atherosclerosis between HIV-positive and HIV-negative groups.
36,801,076
The relationship between state-level structural racism and disparities between the non-hispanic black and non-hispanic white populations in multiple health outcomes.
While several studies have examined the impact of individual indicators of structural racism on single health outcomes, few have explicitly modeled racial disparities in a wide range of health outcomes using a multidimensional, composite structural racism index. This paper builds on the previous research by examining the relationship between state-level structural racism and a wider array of health outcomes, focusing on racial disparities in mortality from firearm homicide, infant mortality, stroke, diabetes, hypertension, asthma, HIV, obesity, and kidney disease. We used a previously developed state structural racism index that consists of a composite score derived by averaging eight indicators across five domains (1) residential segregation (2) incarceration (3) employment (4) economic statuswealth and (5) education. Indicators were obtained for each of the 50 states using Census data from 2020. We estimated the Black-White disparity in each health outcome in each state by dividing the age-adjusted mortality rate for the non-Hispanic Black population by the age-adjusted mortality rate for the non-Hispanic White population. These rates were obtained from the CDC WONDER Multiple Cause of Death database for the combined years 1999-2020. We conducted linear regression analyses to examine the relationship between the state structural racism index and the Black-White disparity in each health outcome across the states. In multiple regression analyses, we controlled for a wide range of potential confounding variables. Our calculations revealed striking geographic differences in the magnitude of structural racism, with the highest values generally being observed in the Midwest and Northeast. Higher levels of structural racism were significantly associated with greater racial disparities in mortality for all but two of the health outcomes. There is a robust relationship between structural racism and Black-White disparities in multiple health outcomes across states. Programs and policies to reduce racial heath disparities must include strategies to help dismantle structural racism and its consequences.
36,800,970
Monkeypox in an immunocompromised patient with underlying human immunodeficiency virus and syphilis infections in Southern Florida of the United States a case report.
The orthopoxvirus causes the rare disease monkeypox, and underlying immune deficiencies might lead to worse outcomes. In this report, we described a rare case of monkeypox with an underlying immune deficiency caused by human immunodeficiency virus infection which was combined with syphilis. This report discusses differences in the initial clinical presentation and clinical course compared to typical monkeypox cases. We report the case of a 32-year-old man with human immunodeficiency virus infection who was admitted to a hospital in Southern Florida. The patient presented to the emergency department with shortness of breath, fever, cough and left-sided chest wall pain. Physical examination revealed a pustular skin rash, consisting of generalised exanthema with small white and red papules. Upon arrival, he was found to be in sepsis with lactic acidosis. Chest radiography showed left-sided pneumothorax and minimal atelectasis in the left mid-lung, with a small pleural effusion at the left lung base. An infectious disease specialist raised the possibility of monkeypox, and the lesion sample tested positive for monkeypox deoxyribonucleic acid. In this case, the possible diagnosis of skin lesions varied because the patient tested positive for syphilis and human immunodeficiency virus. For that reason, the differential diagnosis of monkeypox infection is prolonged owing to its initial atypical clinical features. Patients with underlying immune deficiency who have human immunodeficiency virus infection and syphilis can present with atypical clinical features and delay proper diagnosis, which can increase the risk of spreading monkeypox in hospitals. Thus, patients with rash and risky sexual behaviour should be screened for monkeypox or other sexually transmitted diseases such as syphilis, and a readily available, rapid, and accurate test is necessary to stop the spread of the disease.
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Impact of the COVID-19 pandemic and the dynamic COVID-zero strategy on HIV incidence and mortality in China.
In response to the coronavirus disease 2019 (COVID-19) pandemic, the Chinese government implemented the dynamic COVID-zero strategy. We hypothesized that pandemic mitigation measures might have reduced the incidence, mortality rates, and case fatality ratios (CFRs) of the human immunodeficiency virus (HIV) in 2020-2022. We collected HIV incidence and mortality data from the website of the National Health Commission of the Peoples Republic of China from January 2015 to December 2022. We compared the observed and predicted HIV values in 2020-2022 with those in 2015-2019 using a two-ratio Z-test. From January 1, 2015, to December 31, 2022, a total of 480,747 HIV incident cases were reported in mainland China, of which 60,906 (per year) and 58,739 (per year) were reported in 2015-2019 (pre-COVID-19 stage) and 2020-2022 (post-COVID-19 stage), respectively. The average yearly HIV incidence decreased by 5.2450% (from 4.4143 to 4.1827 per 100,000 people, p < 0.001) in 2020-2022 compared with that in 2015-2019. However, the average yearly HIV mortality rates and CFRs increased by 14.1076 and 20.4238%, respectively (all p < 0.001), in 2020-2022 compared with those in 2015-2019. During the emergency phase in January 2020 to April 2020, the monthly incidence was significantly lower (23.7158%) than that during the corresponding period in 2015-2019, while the incidence during the routine stage in May 2020-December 2022 increased by 27.4334%, (all p < 0.001). The observed incidence and mortality rates for HIV decreased by 16.55 and 18.1052% in 2020, by 25.1274 and 20.2136% in 2021, and by 39.7921 and 31.7535% in 2022, respectively, compared with the predicted values, (all p < 0.001). The findings suggest that Chinas dynamic COVID-zero strategy may have partly disrupted HIV transmission and further slowed down its growth. Without Chinas dynamic COVID-zero strategy, HIV incidence and deaths in the country would have likely remained high in 2020-2022. There is an urgent need to expand and improve HIV prevention, care, and treatment, as well as surveillance in the future.
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Induced abortions of women living with HIV in Finland 1987-2019 a national register study.
Recent data on the rate and risk factors of induced abortion among women living with HIV (WLWH) are limited. Our aim was to use Finnish national health register data to 1) determine the nationwide rate of induced abortions of WLWH in Finland during 1987-2019, 2) compare the rates of induced abortions before and after HIV diagnosis over different time periods, 3) determine the factors associated with terminating a pregnancy after HIV diagnosis, and 4) estimate the prevalence of undiagnosed HIV at induced abortions to see whether routine testing should be implemented. A retrospective nationwide register study of all WLWH in Finland 1987-2019 (n 1017). Data from several registers were combined to identify all induced abortions and deliveries of WLWH before and after HIV diagnosis. Factors associated with terminating a pregnancy were assessed with predictive multivariable logistic regression models. The prevalence of undiagnosed HIV at induced abortion was estimated by comparing the induced abortions among WLWH before HIV diagnosis to the number of induced abortions in Finland. Rate of induced abortions among WLWH decreased from 42.8 to 14.7 abortions1000 follow-up years from 1987-1997 to 2009-2019, more prominently in abortions after HIV diagnosis. After 1997 being diagnosed with HIV was not associated with an increased risk of terminating a pregnancy. Factors associated with induced abortion in pregnancies that began after HIV diagnosis 1998-2019 were being foreign-born (OR 3.09, 95% CI 1.55-6.19), younger age (OR 0.95 per year, 95% CI 0.90-1.00), previous induced abortions (OR 3.36, 95% CI 1.80-6.28), and previous deliveries (OR 2.13, 95% CI 1.08-4.21). Estimated prevalence of undiagnosed HIV at induced abortion was 0.008-0.029%. Rate of induced abortions among WLWH has decreased. Family planning should be discussed at every follow-up appointment. Routine testing of HIV at all induced abortions is not cost-effective in Finland due to low prevalence.
36,800,896
Association between Time to Antiretroviral Therapy and Loss to Care Among Newly Diagnosed Rwandan People Living with Human Immunodeficiency Virus.
Despite improved clinical outcomes of initiating antiretroviral therapy (ART) soon after diagnosis, conflicting evidence exists regarding the impact of same day ART initiation on subsequent clinical outcomes. We aimed to characterize the associations of time to ART initiation with loss to care and viral suppression in a cohort of newly-diagnosed people living with HIV (PLHIV) entering care after Rwanda implemented a national Treat All policy. We conducted a secondary analysis of routinely collected data of adult PLHIV enrolling in HIV care at 10 health facilities in Kigali, Rwanda. Time from enrollment to ART initiation was categorized as same day, 1-7 days, or >7 days. We examined associations between time to ART and loss to care (>120 days since last health facility visit) using Cox proportional hazards models, and between time to ART and viral suppression using logistic regression. Of 2,524 patients included in this analysis, 1,452 (57.5%) were female and the median age was 32 (IQR 26-39). Loss to care was more frequent among patients who initiated ART on the same day (15.9%), compared to those initiating ART 1-7 days (12.3%) or >7 days (10.1%), p<0.001. In multivariable analyses, same-day ART initiation was associated with a greater hazard of loss to care compared to initiating >7 days after enrollment (aHR 1.39, 95% CI 1.04, 1.85). 1,698 (67.3%) had available data on viral load measured within 455 days after enrollment. Of these, 1,476 (87%) were virally suppressed. A higher proportion of patients initiating ART on the same day were virally suppressed (89%) compared to those initiating 1-7 days (84%) or >7 days (88%) after enrollment. This association was not statistically significant. Our findings suggest that ensuring adequate, early support for PLHIV initiating ART rapidly may be important to support retention in care for newly-diagnosed PLHIV in the era of Treat All.
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Universal Repeat Screening for Human Immunodeficiency Virus in the Third Trimester of Pregnancy A Cost-Effectiveness Analysis.
To assess the cost effectiveness of universal repeat screening for human immunodeficiency virus (HIV) infection in the third trimester of pregnancy. A decision-analytic model was constructed to compare two strategies screening for HIV infection in the first trimester alone compared with the addition of repeat screening in the third trimester. Probabilities, costs, and utilities were derived from the literature and varied in sensitivity analyses. The assumed incidence of HIV infection in pregnancy was 0.0145% or 14.5 per 100,000. Outcomes included costs (in 2022 U.S. dollars), maternal and neonatal quality-adjusted life-years (QALYs), and cases of neonatal HIV infection. Our theoretical cohort contained 3.8 million pregnant individuals, the approximate number of births per year in the United States. The willingness-to-pay threshold was set at $100,000QALY. We performed univariable and multivariable sensitivity analyses to determine inputs that most influenced the model. Universal third-trimester screening prevented 133 cases of neonatal HIV infection in this theoretical cohort. Universal third-trimester screening led to an increased cost of $17.54 million and 2,732 increased QALYs, with an incremental cost-effectiveness ratio of $6,418.56 per QALY, less than the willingness-to-pay threshold. In a univariate sensitivity analysis, third-trimester screening remained cost effective with variation of HIV incidence in pregnancy to as low as 0.0052%. In a theoretical U.S.-based cohort of pregnant individuals, universal repeat screening for HIV infection in the third trimester was found to be cost effective and to reduce vertical transmission of HIV. These results merit consideration of a broader HIV-screening program in the third trimester.
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Prospective evaluation of radiographic manifestations of tuberculosis in relationship with CD4 count in patients with HIVAIDS.
A major risk factor to develop active tuberculosis (TB) is the infection with the human immunodeficiency virus (HIV). Chest radiography is the first-line imaging modality used to rule out TB. Coinfected individuals present often with atypical imaging patterns, due to the immunosuppression caused by the virus, making diagnosis difficult. In this prospective observational study 268 TB and HIV coinfected patients were included. During a follow-up period of 24 weeks, the predominant patterns on chest radiography were analyzed and compared to the cluster of differentiation 4 (CD4) count under antiretroviral and anti-TB therapy. Patients with low CD4 counts (<200 cellsµL) showed more often lymphadenopathy (62% vs 38%P .08) and a miliary pattern (64% vs 36%P .04) but less likely cavitation (32% vs 68%P .008) or consolidation (47% vs 63%P .002) compared to individuals with higher CD4 counts. Over the follow-up period, partial response to therapy was the most frequent radiological evolution (62%), mainly accompanied by an increase of CD4 cells (92%). Patients with a decrease in CD4 count mostly presented with a worsening in radiological findings (53%). Radiographic TB manifestation correlated with the immune status of patients coinfected with HIV. Low CD4 counts often showed atypical manifestation.
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Prevalence and incidence of hypertension in a heavily treatment-experienced cohort of people living with HIV in Uganda.
The effect of long-term exposure to antiretroviral therapy (ART) on hypertension in sub-Saharan Africa remains unclear. We aimed to determine the prevalence and incidence of hypertension in people living with HIV (PLWH) with more than 10 years of ART in Uganda. The analysis was performed within a cohort of adult PLWH with more than 10 years of ART at an HIV clinic in Kampala, Uganda. Participants were eligible for this analysis if they had ≥2 follow-up visits. Hypertension was defined as two consecutive systolic blood pressure (SBP) measures greater than 140 mmHg andor diastolic blood pressure (DBP) greater than 90 mmHg, andor documented diagnosis andor the initiation of antihypertensives. We determined the proportion of PLWH with hypertension at baseline and used multivariable logistic regression to determine the factors associated with prevalent hypertension. To determine the incidence of hypertension, follow-up began from the cohort baseline date and was censored at the last clinic visit or date of the event, whichever occurred earlier. Multivariable Poisson regression was used to determine the adjusted incidence rate ratios (aIRR) of hypertension according to demographic, ART, and clinical characteristics. Of the 1000 ALT participants, 970 (97%) had ≥2 follow-up visits, and 237 (24.4%) had hypertension at baseline. The odds of prevalent hypertension were 1.18 for every 5-year increase in age (adjusted odds ratio (aOR) 1.18, 95% CI 1.10-1.34) and were higher among males (aOR 1.70, 95% CI 1.20-2.34), participants with diabetes mellitus (aOR 2.37, 95% CI 1.10-4.01), obesity (aOR 1.99, 95% CI 1.08-3.60), high cholesterol (aOR 1.47, 95% CI 1.16-2.01), and those with prior exposure to stavudine (aOR 2.10, 95% CI 1.35-3.52), or nevirapine (aOR 1.90, 95% CI 1.25-3.01). Of the 733 participants without hypertension at baseline, 116 (15.83%) developed hypertension during 4671.3 person-years of follow-up (incidence rate 24.8 per 1000 person-years 95% CI 20.7-29.8). The factors associated with incident hypertension were obesity (adjusted incidence rate ratio (aIRR) 1.80, 95% CI 1.40-2.81), older age (aIRR 1.12 per 5-year increase in age, 95% CI 1.10,1.25), and renal insufficiency (aIRR1.80, 95% CI 1.40-2.81). The prevalence and incidence of hypertension were high in this heavily treated PLWH cohort. Therefore, with increasing ART coverage, HIV programs in SSA should strengthen the screening for hypertension in heavily treated PLWH.
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Effectiveness, acceptability, and feasibility of technology-enabled health interventions for adolescents living with HIV in low- and middle-income countries A systematic review protocol.
Adolescents living with chronic conditions such as HIV (ALHIV) are challenged to remain adherent and engaged in HIV care. Technology offers a promising platform to deliver behaviour-change interventions to adolescents. The largest proportion of ALHIV resides in sub-Saharan Africa yet little is known about the effectiveness, feasibility and acceptability of technology-enabled interventions to deliver and support health care to ALHIV in resource-constraint settings. This study aims to explore the literature and synthesise the evidence for the effectiveness, acceptability, and feasibility of technology-enabled health interventions for ALHIV in low and middle-income countries (LMIC). Eight electronic databases (Ebscohost, CINAHL, ERIC, MEDLINE, PubMed, SCOPUS, Science Direct, and Sabinet) and Google Scholar will be searched to identify technology-enabled health interventions for ALHIV in LMIC published from 2010-2022. Quantitative and qualitative studies reporting on technology-enabled health interventions for predominantly adolescents (10-19 years) will be included. The review will be performed, and findings reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols. A two-stage process of screening titles and abstracts, and then full-text, will be performed independently by two reviewers. The quality of the included studies will be assessed using the Critical Appraisal Skills Programme checklists, and the Risk of Bias in Non-randomised Studies of Interventions tool will be used to assess the risk of bias. The review will involve publications already in the public domain therefore, ethics approval is not required. The results will be disseminated through a peer-reviewed journal publication andor conference proceedings. PROSPERO registration number CRD42022336330.
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The anti-caspase 1 inhibitor VX-765 reduces immune activation, CD4
HIV-1 infection results in the activation of inflammasome that may facilitate viral spread and establishment of viral reservoirs. We evaluated the effects of the caspase-1 inhibitor VX-765 on HIV-1 infection in humanized NSG mice engrafted with human CD34 The human immunodeficiency virus (HIV) affects millions of people across the world, and has caused over forty million deaths. HIV attacks the immune system, eventually leading to lower levels of immune cells, which prevent the body from fighting infections. One of the early effects of HIV infection is inflammation, an immune process that helps the body remove foreign invaders like viruses. Unfortunately, long term inflammation can lead to serious conditions like cardiovascular disease and cancer. Doctors manage HIV using a class of drugs known as antiretrovirals. These drugs reduce the amount of virus in the body, but they cannot eliminate it entirely. This is because, in the early days of infection, copies of the virus build up in certain organs and tissues, like the gut, forming viral reservoirs. Antiretroviral drugs cannot reach these reservoirs to eliminate them, making a cure for HIV out of reach. One way to address this problem is to develop a new class of drugs that can stop the virus from forming these reservoirs in the first place. Amand et al. wanted to see whether they could reduce the amount of viral reservoirs that form in HIV patients by interrupting a process called inflammasome activation, which occurs early after HIV infection. Inflammasomes are viral detectors that play a role in both inflammation and the formation of viral reservoirs. They activate an enzyme called caspase-1, which in turn activates proteins called cytokines. These cytokines go on to stimulate further inflammation. Amand et al. wanted to see whether a drug called VX-765, which blocks the activity of the caspase-1 enzyme, could reduce inflammation and stop the formation of viral reservoirs. To do this, Amand et al. first ‘humanized’ mice, by populating them with human immune cells, so they could become infected with HIV. They then infected these mice with HIV, and proceeded to treat them with VX-765 two days after infection. The results showed that these mice had fewer viral reservoirs, lower levels of cytokines and higher numbers of immune cells than untreated mice. The findings of Amand et al. show that targeting inflammasome activation early after infection could be a promising strategy for treating HIV. Indeed, if similar results were obtained in humans, then this technique may be the road towards a cure for this virus. In any case, it is likely that combining drugs like VX765 with antiretrovirals will improve long term outcomes for people with HIV.
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Salt Taste and Salt Sensitive Hypertension in HIV.
To provide a summary of current literature and propose potential mechanistic models to help us understand the role of HIV infectionantiretroviral therapy (ART), salt taste sensitivity (STS), and salt sensitivity of blood pressure (SSBP) in hypertension development. The epithelial sodium channel (ENaC) is the main proteinsodium channel for recognizing Na in the tongue and mediates preference to low-medium salt concentrations in animals and humans. Considering the pressor response to oral salt in individuals with SSBP, poor STS may worsen blood pressure. Specific genetic variants in ENaC are linked to salt taste perception and hypertension. HIV infection, some ART, and specific antihypertensive drugs are associated with reduced STS and an increased liking for salty foods. Persons with HIV (PWH) on ART may have a decreased STS and are at a higher risk of developing salt-sensitive hypertension. Inflammation mediated by dietary salt is one of the drivers of poor STS and salt-sensitive hypertension among PWH.
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Information, Motivation, Behavioral Skills Model in Youth Newly Starting Antiretroviral Treatment.
An understanding of adherence among youth newly starting antiretroviral therapy (ART) is critical but understudied. The information-motivation-behavioral skills (IMB) model is often used to understand health behaviors, but has rarely been studied in youth with HIV. In a multi-site sample of 153 youth newly starting ART, structural equation modeling was utilized to test this model. The model was generally supported with information and behavioral skills directly related to the decision to adhere, while motivation was indirectly related through behavioral skills. Results suggest that interventions focusing on improving IMB constructs for medication adherence are important for preventing non-adherence in youth newly starting ART. El entendimiento de la adherencia en jóvenes que recién comienzan ART es fundamental, pero se ha estudiado poco. El modelo de información-motivación-habilidades conductuales (IMB, por sus siglas en inglés) se usa a menudo para comprender los comportamientos de salud, pero rara vez se ha estudiado en jóvenes que viven con el VIH. En una muestra de múltiples sitios de 153 jóvenes que recién comenzaban ART, se utilizó el análisis de ecuaciones estructurales para probar este modelo. En general, el modelo fue apoyado con información y habilidades conductuales directamente relacionadas con la decisión de adherirse, mientras que la motivación se relacionó indirectamente a través de las habilidades conductuales. Los resultados sugieren que las intervenciones que se enfocan en mejorar los aspectos del modelo IMB para la adherencia al medicamento son importantes para prevenir la falta de adherencia en los jóvenes que recién comienzan ART.
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Motivations for blood donation by HIV-positive individuals on antiretrovirals in South Africa A qualitative study.
We performed a mixed-methods study to explore the motivations associated with blood donation by donors with known, but undisclosed HIV-positive status and ARV use (HIVARV), seeking potential strategies to reduce such donations and mitigate risk for blood recipients. Here, we report predominantly the qualitative component. A safe and sustainable blood supply is dependent in part, on effective pre-donation donor assessment. We previously described failure by HIVARV blood donors to disclose their status. Such donations may lead to transfusion-transmitted HIV. The social ecological model provided the conceptual framework for this study. Previously identified HIVARV donors were invited to complete a survey (including a validated stigma scale) and qualitative interview, which underwent inductive and deductive thematic analysis. We uncovered two primary motivational paths to HIVARV blood donations privacy and altruism. The latter included a motivation not previously reported in the literature donating specifically for other people living with HIV (PLWH). The other primary factor was a lack of privacy. These accounts often included donors encountering donation opportunities when accompanied by people to whom they had not and did not plan to disclose their HIV status. Most were highly confident their donations would be identified as HIV-positive and discarded. We demonstrated a complex interaction between individual, social, cultural, and structuralpolicy factors in blood donations by PLWH who take ARV. Recommendations to limit HIV ARV donations include (1) Targeted communication strategies to increase knowledge among PLWH of their deferral from blood donation-without increasing stigma, and (2) development of procedures to assist those who feel unable to opt-out of donation due to privacy concerns.
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HIV-PASS (Pain and Sadness Support) Randomized controlled trial of a behavioral health intervention for interference due to pain in people living with HIV, chronic pain, and depression.
To determine whether HIV-Pain and Sadness Support (HIV-PASS), a collaborative behavioral health intervention based on behavioral activation, is associated with decreased pain-related interference with daily activities, depression, and other outcomes in people living with HIV. We conducted a three-site clinical trial (n 187) in which we randomly assigned participants to receive either HIV-PASS or health education (HE) control condition. In both conditions, participants received seven intervention sessions, comprised of an initial in-person joint meeting with the participant, their HIV primary care provider and a behavioral health specialist (BHS), and six, primarily telephone-based, meetings with the BHS and participant. The intervention period lasted three months and follow-up assessments were conducted for an additional nine months. Compared to HE, HIV-PASS was associated with significantly lower pain-related interference with daily activities at the end of month 3 (our primary outcome b -1.31, 95% CI -2.28, -0.34). We did not observe other differences between groups at three months in secondary outcomes that included worst or average pain in the past week, depression symptoms, anxiety, and perceived overall mental and physical health. There were no differences between groups on any outcomes at 12 months post-enrollment. A targeted intervention can have positive effects on pain interference. At the end of intervention, effects we found were in a clinically significant range. However, effects diminished once the intervention period ended.Trial Registration ClinicalTrials.gov NCT02766751.
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Hepatitis C Among People Who Inject Drugs (PWID) in Latin America and the Caribbean A Meta-Analysis of Prevalence Over Three Decades.
People who inject drugs (PWID) are known to be more susceptible to infections such as hepatitis C virus (HCV). This systematic review and meta-analysis aimed to estimate the prevalence of hepatitis C among PWID in Latin America and the Caribbean (LAC). The MEDLINE, Embase, and LILACS databases were searched without language restriction from inception to 2021. Articles were screened based on titles and abstracts. After reading the full texts, the articles were selected based on eligibility criteria. Of the 486 identified publications, 123 full texts were assessed, and 23 studies with a mean quality score of 7.2 were included. A total of 11,419 PWID were included in the meta-analysis, and the estimated overall prevalence of hepatitis C among PWID in LAC was 57.0%, which was higher than the United Nations Office on Drugs and Crime global prevalence of 50.2%. In meta-analyses of subgroups divided according to the risk of exposure to HCV infection (in addition to the imminent risk of injected drugs), the estimated prevalence of hepatitis C in PWID in the lowerrisk population (general) was 57.0%. The prevalence of hepatitis C in PWID who were infected with HIV was 61.0%. The estimated hepatitis C prevalence was also assessed for three periods in 1991-2000, it was 59.0% in 2001-2010, it was 63.0% and in 2011-2020, it was 48.0%. The high estimated prevalence of hepatitis C in LAC reinforces the need for increased diagnostic efforts, strategies for treating drug addiction and hepatitis C, and harm reduction policies that target PWID.
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Polysubstance Use Patterns Associated With HIV Disease Severity Among Those With Substance Use Disorders A Latent Class Analysis.
Polysubstance use is common among people with HIV infection (PWH) and with substance use disorder (SUD), but its effects are understudied. We aimed to identify polysubstance use patterns over time and assess their associations with HIV disease severity. In 233 PWH with current or past SUD, latent class analysis identified polysubstance use patterns based on the Alcohol Use Disorders Identification Test-Consumption and past-30-day use of cannabis, cocaine, opioids, and tranquilizers at baseline. We categorized changes in use patterns and tested associations between those changes and CD4 count and HIV viral suppression at 12 months in linear and logistic regressions. Three patterns were identified at baseline 18% did not use any substance (NONE--a priori defined) 63% used mostly cannabis and alcohol (CA) and 19% used opioids along with other drugs, including cocaine, tranquilizers, cannabis, and alcohol (MULTI). At 12 months, 40% moved from a high to a lower substance use class (MULTI to CA, either to NONE) or remained as NONE, 43% were in CA both times and 17% increased (NONE to CA, either to MULTI) or remained as MULTI. The adjusted mean CD4 count (for baseline covariates and baseline CD4 count) was significantly lower among participants increasing or remaining in MULTI (523, 95% CI 448, 598, cellsmm3) compared with those who decreasedabstained throughout (607, 95% CI 552, 663, We identified distinct polysubstance use patterns among PWH with SUD cannabisalcohol and opioids with alcohol and other drugs. Changes over time toward fewer substancesno use were associated with lower HIV disease severity based on CD4 count but not based on HIV viral suppression.
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Effect of Covid-19 lockdowns on identification of advanced HIV disease in outpatient clinics in Uganda.
Using data from 67 Ugandan HIV clinics (July 2019-January 2022), we report a 40% (1,0051,662) reduction in the number of people with HIV presenting to care after August 2021 compared to pre-pandemic levels, with a greater proportion presenting with advanced HIV disease (20% vs. 16% in the pre-Covid period).
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Syndemics and non infectious diseases.
The concept of syndemics is getting more and more popularity in scientific journals, especially since the end of the first decade of the current century. It relates to the dynamic interaction of synchronous or sequential diseases (whether communicable or not, also including mental diseases), with social and environmental factors, resulting at the end in a worse global outcome. A first article in the same Journal (1) was devoted to infectious diseases, especially COVID-19 and HIV infections. In this second article, we highlight the fact that the concept is also applicable on diseases which are not transmitted by infectious pathogens. The importance of considering action within the field of social determinants of care will be illustrated by a limited selection of examples. Le concept de «syndémie» - l’interaction entre maladies co-existantes ou séquentielles (transmissibles, non transmissibles, et maladies mentales), avec des phénomènes sociaux et environnementaux qui amplifient les effets négatifs de cette interaction - fait de plus en plus l’objet de publications dans des journaux internationaux, particulièrement ces dernières années. Un premier article dans cette même Revue (1) avait ciblé plus particulièrement les maladies infectieuses, en particulier les infections COVID-19 et HIV. Dans ce deuxième article, nous soulignons que le concept est aussi d’application pour des maladies non infectieuses. L’importance de la prise en charge des déterminants sociaux de la santé est illustré par quelques exemples choisis.
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Impact of alcohol use disorder severity on human immunodeficiency virus (HIV) viral suppression and CD4 count in three international cohorts of people with HIV.
Alcohol use has been linked to worse human immunodeficiency virus (HIV) immunologicvirologic outcomes, yet few studies have explored the effects of alcohol use disorder (AUD). This study assessed whether AUD severity is associated with HIV viral suppression and CD4 count in the three cohorts of the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIVAIDS (URBAN ARCH) Consortium. People with HIV (PWH) in Uganda (n 301), Russia (n 400), and Boston (n 251), selected in-part based on their alcohol use, were included in analyses. Logistic and linear regressions were used to assess the cross-sectional associations between AUD severity (number of DSM-5 diagnostic criteria) and (1) HIV viral suppression, and (2) CD4 count (cellsmm The proportion of females was 51% (Uganda), 34% (Russia), and 33% (Boston) mean age (SD) was 40.7 (9.6), 38.6 (6.3), and 52.1 (10.5), respectively. All participants in Uganda and all but 27% in Russia and 5% in Boston were on antiretroviral therapy. In Uganda, 32% met criteria for AUD, 92% in Russia, and 43% in Boston. The mean (SD) number of AUD criteria was 1.6 (2.4) in Uganda, 5.6 (3.3) in Russia, and 2.4 (3.1) in Boston. Most participants had HIV viral suppression (Uganda 92%, Russia 57%, Boston 87%) median (IQR) CD4 count was 673 (506, 866), 351 (201, 542), and 591 (387, 881), respectively. In adjusted models, there were no associations between AUD severity and HIV viral suppression adjusted odds ratios (AOR) (95%CI) per 1 additional AUD criterion in Uganda was 1.08 (0.87, 1.33) Russia 0.98 (0.92, 1.04) and Boston 0.95 (0.84, 1.08) or CD4 count mean difference (95%CI) per 1 additional criterion 5.78 (-7.47, 19.03), -3.23 (-10.91, 4.44), and -8.18 (-24.72, 8.35), respectively. In three cohorts of PWH, AUD severity was not associated with HIV viral suppression or CD4 count. PWH with AUD in the current era of antiretroviral therapy can achieve virologic control.
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Using a Bioactive
The known
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Nanobody-mediated complement activation to kill HIV-infected cells.
The complement system which is part of the innate immune response against invading pathogens represents a powerful mechanism for killing of infected cells. Utilizing direct complement recruitment for complement-mediated elimination of HIV-1-infected cells is underexplored. We developed a novel therapeutic modality to direct complement activity to the surface of HIV-1-infected cells. This bispecific complement engager (BiCE) is comprised of a nanobody recruiting the complement-initiating protein C1q, and single-chain variable fragments of broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope (Env) protein. Here, we show that two anti-HIV BiCEs targeting the V3 loop and the CD4 binding site, respectively, increase C3 deposition and mediate complement-dependent cytotoxicity (CDC) of HIV-1 Env-expressing Raji cells. Furthermore, anti-HIV BiCEs trigger complement activation on primary CD4 T cells infected with laboratory-adapted HIV-1 strain and facilitates elimination of HIV-1-infected cells over time. In summary, we present a novel approach to direct complement deposition to the surface of HIV-1-infected cells leading to complement-mediated killing of these cells.
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Are human papillomavirus knowledge and vaccine uptake associated with HIV status and social determinants of health in young sexual minority men
This brief report examines the relationship, if any, between human immunodeficiency virus (HIV) status, and individual-level and socio-sexual partner-level factors of social determinants of health (SDOH) that are associated with human papillomavirus (HPV) knowledge and vaccine uptake in young sexual minority men (YSMM). We used data from 126 YSMM recruited by network-based sampling during 2015-2016 in Houston, Texas. Descriptive statistics and regression analyses were conducted to test the association between HIV status, SDOH, and HPV knowledge and vaccine uptake. Those living with HIV had lower odds of knowledge of HPV-associated anal cancer (OR 0.43, 95% CI 0.18-0.97) and knowledge of HPV spreading via sexual contact (OR 0.11, 95% CI 0.01-0.64), and higher odds of HPV vaccine uptake (OR 2.90, 95% CI 1.11-8.02). HPV knowledge and vaccine uptake in YSMM was not associated with partners attributes or individuals SDOH factors in our study yet was significantly associated with HIV status. Future interventions are needed to increase HPV knowledge among individuals living with HIV and vaccine uptake particularly among YSMM living without HIV that are not engaged in healthcare.
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Nanoscale Interaction Mechanisms of Antiviral Activity.
Nanomaterials have now found applications across all segments of society including but not limited to energy, environment, defense, agriculture, purification, food medicine, diagnostics, and others. The pandemic and the vulnerability of humankind to emerging viruses and other infectious diseases has renewed interest in nanoparticles as a potential new class of antivirals. In fact, a growing body of evidence in the literature suggests nanoparticles may have activity against multiple viruses including HIV, HNV, SARS-CoV-2, HBV, HCV, HSV, RSV, and others. The most described antiviral nanoparticles include copper, alloys, and oxides including zinc oxide (ZnO), titanium oxide, iron oxide, and their composites, nitrides, and other ceramic nanoparticles, as well as gold and silver nanoparticles, and sulfated and nonsulfated polysaccharides and other sulfated polymers including galactan, cellulose, polyethylenimine, chitosanchitin, and others. Nanoparticles, synthesized via the biological or green method, also have great importance and are under major consideration these days, as their method of synthesis is easy, reliable, cost-effective, efficient, and eco-friendly, and is done using easily available sources such as bacteria, actinomycetes, yeast, fungi, algae, herbs, and plants, in comparison to chemically mediated synthesis. Chemical synthesis is highly expensive and involves toxic solvents, high pressure, energy, and high temperature conversion. Examples of biologically synthesized NPs include iron oxide, Cu and CuO NPs, and platinum and palladium NPs. In contrast to traditional medications, nanomedications have multiple advantages their small size, increased surface to volume ratio, improved pharmacokinetics, improved biodistribution, and targeted delivery. In terms of antiviral activity, nanoscale interactions represent a unique mode of action. As reviewed here their biomedical application as an antiviral has shown four major mechanisms (1) direct viral interaction prohibiting the virus from infecting the cell, (2) interaction to receptor or cell surface preventing the virus from entering the host cells, (3) preventing the replication of the virus, or (4) other processing mechanisms which inhibit the spread of virus. Here these pharmacologic mechanisms are reviewed and the challenges for technology translation are discussed in more detail.
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The role of structural factors for preventing HIV risk practices among adolescents in South Africa A three-wave analysis of caregiving, education, food security, and social protection.
Structural interventions are endorsed to enhance biomedical and behavioural HIV prevention programmes for adolescents. Aiming to inform future interventions, we evaluated longitudinal associations between six structural factors and five HIV risk practices in a cohort of adolescents in South Africa. We used three rounds of data between 2014-2018 on 1046 adolescents living with HIV and 483 age-matched community peers in South Africas Eastern Cape (Observations 4402). We used multivariable random effects within-between logistic regression to estimate sex-specific associations between six time-varying structural factors - number of social grants, education enrolment, days with enough food, caregiver supervision, positive caregiving, and adolescent-caregiver communication - and five HIV risk practices - multiple sexual partners, transactional sex, age-disparate sex, condomless sex, and sex on substances. We calculated probability differences, contrasting predicted probabilities at average and maximum values of structural factors associated with multiple risk practices. The sample mean age was 15.29 (SD 3.23) years and 58% were female. In females, compared to average, maximum positive caregiving scores were associated with lower probability of transactional sex (-1.06 percentage points ppts, 95%CI-1.60 -0.52ppts), and age-disparate sex (-0.73ppts 95%CI-1.26 -0.19ppts) maximum caregiver supervision scores were associated with lower probability of multiple sexual partners (-3.11ppts 95%CI-3.87 -2.35ppts) transactional sex (-1.07ppts, 95%CI-1.42 -0.71ppts), age-disparate sex (-0.67ppts 95%CI-1.08 -0.25ppts), condomless sex (-3.96ppts 95%CI-5.65 -2.26ppts), and sex on substances (-0.93ppts 95%CI-1.50 -0.37ppts) and, seven days with enough food was associated with lower probability of multiple sexual partners (-1.18ppts, 95%CI-2.06 -0.30ppts), and transactional sex (-0.91ppts 95%CI-1.41 -0.42ppts). Relative to non-enrolment, education enrolment was associated with lower probability of age-disparate sex (-3.18ppts 95%CI-5.35 -1.01ppts), and condomless sex (-11.32ppts 95%CI-19.15 -3.49ppts). In males, compared to average, maximum caregiver supervision scores were associated with lower probability of multiple sexual partners (-2.83ppts 95%CI-3.66 -2.00ppts), transactional sex (-0.90ppts 95%CI-1.20 -0.60ppts), age-disparate sex (-0.46ppts 95%CI-0.77 -0.15ppts), and sex on substances (-1.42ppts 95%CI-2.06 -0.78ppts). No other structural factors were associated with multiple risk practices. Structural interventions to improve food security and education enrolment among adolescent girls, and positive and supervisory caregiving among adolescent girls and boys are likely to translate into crucial reductions in HIV risk.
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Transmissibility of clinically relevant atovaquone-resistant
Rising numbers of malaria cases and deaths underscore the need for new interventions. Long-acting injectable medications, such as those now in use for HIV prophylaxis, offer the prospect of a malaria chemical vaccine, combining the efficacy of a drug (like atovaquone) with the durability of a biological vaccine. Of concern, however, is the possible selection and transmission of drug-resistant parasites. We addressed this question by generating clinically relevant, highly atovaquone-resistant, New tools are needed to protect individuals from malaria and to control malaria in the field. Atovaquone plus proguanil is a commonly used and well-tolerated medicine to prevent malaria. No drug resistance has been reported from its prophylactic use, but tablets must be taken daily. Giving atovaquone as a single injection may provide much longer-lasting protection, against both falciparum and vivax malaria, but there is concern this may create drug resistance. In this study we showed that clinically relevant atovaquone-resistant malaria parasites survive poorly, if at all, in mosquitoes, and that mosquitoes do not transmit drug-resistant parasites to humanized mice. These findings lessen the likelihood that an atovaquone chemical vaccine would lead to the spread of atovaquone resistance.
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Aminobisphosphonates reactivate the latent reservoir in people living with HIV-1.
Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure HIV-1 infection include shock and kill strategies to disrupt latency using small molecules or latency-reversing agents (LRAs) to induce expression of HIV-1 enabling cytotoxic immune cells to eliminate infected cells. The modest success of current LRAs urges the field to identify novel drugs with increased clinical efficacy. Aminobisphosphonates (N-BPs) that include pamidronate, zoledronate, or alendronate, are the first-line treatment of bone-related diseases including osteoporosis and bone malignancies. Here, we show the use of N-BPs as a novel class of LRA we found in
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Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4
Type I interferon (IFN) upregulates proteins that inhibit HIV within infected cells. Prior studies have identified IFN-stimulated genes (ISGs) that impede lab-adapted HIV in cell lines, yet the ISG(s) that mediate IFN restriction in HIV target cells, primary CD4
36,798,211
HIV and gender identity expression among transfeminine women in the Western Cape, South Africa - a thematic analysis of data from the HPTN 071 (PopART) trial.
Transfeminine women in South Africa have a high HIV risk due to structural, behavioural, and psychosocial factors. Transfeminine women and feminine identifying men who have sex with men (MSM) are often conflated or grouped with transgender or MSM categories in HIV service programming, although they dont necessarily identify as either. We aimed to investigate gender expression among feminine identifying people who were assigned male at birth. We examined how local conceptualizations of sexuality and gender intersect with the key population label of transgender imported into local HIV programming. A qualitative cohort nested within the HPTN 071 (PopART) trial included longitudinal, in-depth interviews with eight transfeminine women (four who disclosed as living with HIV). Data were collected approximately every six weeks between January 2016 and October 2017. We discuss gender identification presented in participants daily lives and in relation to HIV service access. Of the eight participants, only one accepted transgender as a label, and even she used varying terms at different times to describe her identity. For participants, a feminine identity included dressing in normatively feminine clothes using feminine terms, pronouns and names and adopting stereotypically feminine mannerisms. Participants would switch between typically feminine and masculine norms in response to contextual cues and audience. For example, some participants accepted identification as masculine gay men amongst their family members, but amongst peers, they expressed a more effeminate identity and with partners they took on a feminine identity. Our findings are amongst the first exploratory and descriptive data of transfeminine women in South Africa. We show how transfeminine women navigate fluid gender identities that could pose a challenge for accessing and utilizing HIV services that are currently set up for transgender individuals or MSM. More work needs to be done to understand and respond to the diverse and shifting ways people experience their gender identities in this high HIV burden context.
36,798,147
Inflammasomes in Human Immunodeficiency Virus Type 1 Infection.
Innate immune responses are the hosts first line of defense against human immunodeficiency virus type 1 (HIV-1) infection, with pattern recognition receptors detecting viral specific pathogen-associated molecular patterns and initiating antiviral responses. In response to HIV-1 nucleic acids or proteins, some pattern recognition receptors have the ability to assemble a large multiprotein complex called the inflammasome, which triggers pro-inflammatory cytokine release and a form of lytic programmed cell death called pyroptosis. Here, we review our current understanding of the mechanism of the inflammasome in sensing HIV-1 infection. Furthermore, we discuss the contribution of inflammasome activation in HIV-1 pathogenesis as well as potential strategies of targeting inflammasome activation for the treatment of HIV-1 infection.
36,798,134
The initial interplay between HIV and mucosal innate immunity.
Human Immunodeficiency Virus (HIV) is still one of the major global health issues, and despite significant efforts that have been put into studying the pathogenesis of HIV infection, several aspects need to be clarified, including how innate immunity acts in different anatomical compartments. Given the nature of HIV as a sexually transmitted disease, one of the aspects that demands particular attention is the mucosal innate immune response. Given this scenario, we focused our attention on the interplay between HIV and mucosal innate response the different mucosae act as a physical barrier, whose integrity can be compromised by the infection, and the virus-cell interaction induces the innate immune response. In addition, we explored the role of the mucosal microbiota in facilitating or preventing HIV infection and highlighted how its changes could influence the development of several opportunistic infections. Although recent progress, a proper characterization of mucosal innate immune response and microbiota is still missing, and further studies are needed to understand how they can be helpful for the formulation of an effective vaccine.
36,798,073
Giant pericardial cyst, an unusual cause of right heart failure in an elderly patient with tuberculosis and HIV A case report.
Pericardial cysts are rare mediastinal masses commonly asymptomatic and incidentally found on chest radiographs. Pericardial cysts may be acquiredinflammatory in origin and may be symptomatic. We present a case of 65-year-old male who presented with symptoms of right heart failure. Diagnosis of a giant pericardial cyst was made using imaging modalities such as chest X-ray, computed tomography scan, and echocardiography. Percutaneous cyst aspiration was done under echocardiography guidance. Radiologists and cardiothoracic surgeons need to understand the pathology of inflammatoryacquired pericardial cysts to include in their differential diagnosis of mediastinal masses.
36,798,044
Psychosocial factors involved in the very rare use of HIV testing among French MSM a cross-sectional study.
Among men who have sex with men (MSM) in France, the average time between infection and testing is too long, leading to late diagnosis. A better understanding of very infrequent HIV testing (VIT i.e. have not tested for at least 6 years) could help reach unknowingly long-infected MSM. Thus, we aim to identify psychosocial factors associated with VIT among MSM in France. We conducted a multivariate regression on the data collected via a cross-sectional survey among 315 MSM. 11.1% ( We call for the development, at the same time, of programs that operate at the individual, institutional and societal levels. In particular, we recommend diversifying the modes of promotion and access to prevention tools, especially for MSM over 50 years old or with little or no connection to the gay community.
36,797,746
Structural violence and the uncertainty of viral undetectability for African, Caribbean and Black people living with HIV in Canada an institutional ethnography.
Biomedical advances in healthcare and antiretroviral treatment or therapy (ART) have transformed HIVAIDS from a death sentence to a manageable chronic disease. Studies demonstrate that people living with HIV who adhere to antiretroviral therapy can achieve viral suppression or undetectability, which is fundamental for optimizing health outcomes, decreasing HIV-related mortality and morbidity, and preventing HIV transmission. African, Caribbean, and Black (ACB) communities in Canada remain structurally disadvantaged and bear a disproportionate burden of HIV despite biomedical advancements in HIV treatment and prevention. This institutional ethnography orients to the concept of structural violence to illuminate how inequities shape the daily experiences of ACB people living with HIV across the HIV care cascade. We conducted textual analysis and in-depth interviews with ACB people living with HIV (n 20) and health professionals including healthcare providers, social workers, frontline workers, and health policy actors (n 15). Study findings produce a cumulative understanding that biomedical HIV discourses and practices ignore structural violence embedded in Canadas social fabric, including legislation, policies and institutional practices that produce inequities and shape the social world of Black communities. Findings show that inequities in structural and social determinants of health such as food insecurity, financial and housing instability, homelessness, precarious immigration status, stigma, racial discrimination, anti-Black racism, criminalization of HIV non-disclosure, health systems barriers and privacy concerns intersect to constrain engagement and retention in HIV healthcare and ART adherence, contributing to the uncertainty of achieving and maintaining undetectability and violating their right to health. Biomedical discourses and practices, and inequities reduce Black people to a stigmatized, pathologized, and impoverished detectable viral underclass. Black people perceived as nonadherent to ART and maintain detectable viral loads are considered bad patients while privileged individuals who achieve undetectability are considered good patients. An effective response to ending HIVAIDS requires implementing policies and institutional practices that address inequities in structural and social determinants of health among ACB people.
36,797,703
Comprehensive sexuality education linked to sexual and reproductive health services reduces early and unintended pregnancies among in-school adolescent girls in Zambia.
Advancing the health of adolescents, particularly their sexual and reproductive health, including HIV prevention and care, is a development imperative. A critical part for improving their wellbeing and economic development is the social status accorded to adolescent girls and young women (AGYW). However, AGYW in many countries including Zambia, encounter health challenges that stem from gender inequalities, lack of empowerment, inaccurate knowledge on sexuality, and poor access to sexual and reproductive health (SRH) services and information. Addressing the knowledge gaps through comprehensive sexuality education (CSE) and improving access to SRH services and appropriate information, should reduce school attrition from early and unintended pregnancies (EUP) and enhance realization of their full potential. The aim was to reduce EUP and improve SRH outcomes among AGYW in Zambia through provision of CSE linked to receptive SRH services. A 3-Arm randomized control study collected cross-sectional data at baseline, midline and Endline. Schools where CSE was being routinely provided were randomized into a non-intervention arm (arm1), an intervention arm in which information on available SRH services was provided in schools by health workers to complement CSE, (arm 2), and arm 3 in which pupils receiving CSE were also encouraged or supported to access pre-sensitized, receptive SRH services. Following 3 years of intervention exposure (CSE-Health Facility linkages), findings showed a significant decline of in-school pregnancies amongst AGYW in both intervention arms, with arm two exhibiting a more significant decline, having recorded only 0.74% pregnancies at endline (p < 0.001), as well as arm 3, which recorded 1.34% pregnancies (p < 0.001). No significant decline was recorded in the CSE only control arm. Trends in decline of pregnancies started to show by midline, and persisted at endline (2020), and when difference in differences test was applied, the incident rate ratios (IRR) between the none and exposed arms were equally significant (p < 0.001). Linking provision of CSE with accessible SRH services that are receptive to needs of adolescents and young people reduces EUP, which provides the opportunity for higher retention in school for adolescent girls. Among Zambia’s key health and development challenges, are high rates of EUP, and disproportionately higher HIV rates among AGYW. Pregnancy among girls in school poses a challenge. CSE programmes are part of available armamentarium to improve knowledge on the risks. Poor SRH places a heavy strain on health systems and undermines sustainable development efforts. In response to these challenges, we initiated implementation research to develop and test a model linking CSE programs in schools with access to SRH services and information. Research was conducted in 23 schools and their local catchment health care facilities in two North Western province districts of Zambia. Following baseline data collection, schools were selected to ensure comparability of indicators such as reported pregnancy rates, CSE, and subsequently randomized into three study arms, with the first arm continuing standard instruction of CSE (control). The second arm was designed to bring information on available SRH services to schools, including raising awareness through health fares and clubs. In the third arm, health providers were trained to be more receptive to ASRH health needs, in addition to encouraging teachers to introduce students to health services. Pregnancies declined in all intervention arms at endline, with marked reductions in intervention Arm 2 which recorded 0.74% of in school pregnancies (p < O.001), followed by arm 3, with 1.34% (p < 0.001). The decline in intervention arms was more than 50% in intervention arms, as compared with control arm, and significantly lower, as a proportion of AGYW in arm 2, followed by arm 3.
36,797,696
Knowledge, attitudes and acceptance of voluntary medical male circumcision among males attending high school in Shiselweni region, Eswatini a cross sectional study.
In countries such as Eswatini, where there is a high HIV prevalence and low male circumcision the World Health Organization and the Joint United Nations Programme for HIVAIDS recommend infant and adult circumcision be implemented. The aim of this study was to assess the knowledge, attitudes and acceptability of voluntary medical male circumcision amongst males attending high school in Eswatini. An observational cross-sectional study was conducted during February and March of 2018 amongst 407 young males (15-21 years) attending Form 4, in nine high schools in the Shiselweni region of Eswatini using a self-administered questionnaire of 42 close ended questions. Sociodemographic details, circumcision status, acceptance of voluntary medical male circumcision, knowledge and attitude scores analysed in Stata® 14 statistical software were described using frequencies, medians and ranges respectively. Bivariate and multivariate linear regression was used to assess the impact of independent variables on circumcision status and acceptance of voluntary medical male circumcision. The level of statistical significance was p < 0.05. Amongst the 407 high school-going males, 48.98% (n 201) reported being circumcised. The majority of the adolescents (75.74% n 306) were knowledgeable about voluntary medical male circumcision. However, an even larger majority (84.90% (n 343) had a negative attitude towards it. In the multivariate logistic regression analysis, having parented their own children (aOR 3.55 95%CI 1.2-10.48), and having circumcised friends (aOR 3.99 95%CI 1.81-8.84) were significantly associated with being circumcised. Neither knowledge nor attitude were associated with the acceptability of voluntary medical male circumcision. In Eswatini male high school students are knowledgeable about voluntary medical male circumcision but have a negative attitude towards it. Having parented their own children, and having circumcised friends influenced being circumcised.
36,797,059
Clinical Reasoning Progressive Hemiparesis and White Matter Abnormalities in a HIV-Negative Patient.
A 61-year-old man from India was admitted to the hospital after being found unresponsive by the roadside. He was treated with dual-antiplatelet therapy for an acute coronary syndrome. Ten days into admission he was noted to have mild left sided face, arm and leg weakness which progressed significantly over the next two months in association with progressive white matter abnormalities on MRI of the brain. Here we review the approach and clinical reasoning that led to the detection of a rare underlying cause of a devastating neurological disease. We also present a novel treatment approach which achieved a sustained clinical and radiological response.
36,796,984
Spatiotemporal variation in risk of Shigella infection in childhood a global risk mapping and prediction model using individual participant data.
Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio OR0·81 95% CI 0·76-0·86) and open defecation decreased them by 18% (OR0·82 0·76-0·88). The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill Melinda Gates Foundation.
36,796,860
Effectiveness of physical activity interventions for improving depression, anxiety and distress an overview of systematic reviews.
To synthesise the evidence on the effects of physical activity on symptoms of depression, anxiety and psychological distress in adult populations. Umbrella review. Twelve electronic databases were searched for eligible studies published from inception to 1 January 2022. Systematic reviews with meta-analyses of randomised controlled trials designed to increase physical activity in an adult population and that assessed depression, anxiety or psychological distress were eligible. Study selection was undertaken in duplicate by two independent reviewers. Ninety-seven reviews (1039 trials and 128 119 participants) were included. Populations included healthy adults, people with mental health disorders and people with various chronic diseases. Most reviews (n77) had a critically low A MeaSurement Tool to Assess systematic Reviews score. Physical activity had medium effects on depression (median effect size-0.43, IQR-0.66 to -0.27), anxiety (median effect size-0.42, IQR-0.66 to -0.26) and psychological distress (effect size-0.60, 95% CI -0.78 to -0.42), compared with usual care across all populations. The largest benefits were seen in people with depression, HIV and kidney disease, in pregnant and postpartum women, and in healthy individuals. Higher intensity physical activity was associated with greater improvements in symptoms. Effectiveness of physical activity interventions diminished with longer duration interventions. Physical activity is highly beneficial for improving symptoms of depression, anxiety and distress across a wide range of adult populations, including the general population, people with diagnosed mental health disorders and people with chronic disease. Physical activity should be a mainstay approach in the management of depression, anxiety and psychological distress. CRD42021292710.
36,796,461
Insights into the oligomeric structure of the HIV-1 Vpu protein.
The HIV-1-encoded protein Vpu forms an oligomeric ion channelpore in membranes and interacts with host proteins to support the virus lifecycle. However, Vpu molecular mechanisms are currently not well understood. Here, we report on the Vpu oligomeric organization under membrane and aqueous conditions and provide insights into how the Vpu environment affects the oligomer formation. For these studies, we designed a maltose-binding protein (MBP)-Vpu chimera protein and produced it in E. coli in soluble form. We analyzed this protein using analytical size-exclusion chromatography (SEC), negative staining electron microscopy (nsEM), and electron paramagnetic resonance (EPR) spectroscopy. Surprisingly, we found that MBP-Vpu formed stable oligomers in solution, seemingly driven by Vpu transmembrane domain self-association. A coarse modeling of nsEM data as well as SEC and EPR data suggests that these oligomers most likely are pentamers, similar to what was reported regarding membrane-bound Vpu. We also noticed reduced MBP-Vpu oligomer stability upon reconstitution of the protein in β-DDM detergent and mixtures of lyso-PCPG or DHPCDHPG. In these cases, we observed greater oligomer heterogeneity, with MBP-Vpu oligomeric order generally lower than in solution however, larger oligomers were also present. Notably, we found that in lyso-PCPG, above a certain protein concentration, MBP-Vpu assembles into extended structures, which had not been reported for Vpu. Therefore, we captured various Vpu oligomeric forms, which can shed light on Vpu quaternary organization. Our findings could be useful in understanding Vpu organization and function in cellular membranes and could provide information regarding the biophysical properties of single-pass transmembrane proteins.
36,796,353
Delivery of Community-based Antiretroviral Therapy to MaintainViral Suppression and Retention in Care in South Africa.
To determine whether the Centralized Chronic Medication Dispensing and Distribution (CCMDD) program in South Africas differentiated ART delivery model impacts clinical outcomes, we assessed viral load (VL) suppression and retention in care between patients participating in the program compared to the clinic-based standard of care. Clinically stable people living with HIV (PLHIV) eligible for differentiated care were referred to the national CCMDD program and followed for up to six months. In this secondary analysis of trial cohort data, we estimated the association between routine patient participation in the CCMDD program and their clinical outcomes of viral suppression (<200 copiesmL) and retention in care. Among 390 PLHIV, 236 (61%) were assessed for CCMDD eligibility, 144 (37%) were eligible, and 116 (30%) participated in CCMDD. Participants obtained their ART in a timely manner at 93% (265286) of CCMDD visits. VL suppression and retention in care was very similar among CCMDD-eligible patients who participated in the program compared to patients who did not participate in the program (aRR 1.03 95% CI 0.94-1.12). VL suppression alone (aRR 1.02 95% CI 0.97-1.08) and retention in care alone (aRR 1.03 95% CI 0.95-1.12) were also similar between CCMDD-eligible PLHIV who participated in the program and those who did not. The CCMDD program successfully facilitated differentiated care among clinically stable participants. PLHIV participating in the CCMDD program maintained a high proportion of viral suppression and retention in care, indicating that community-based ART delivery model did not negatively impact their HIV care outcomes.
36,796,320
A clinical review of mpox for the Aotearoa New Zealand clinician.
The World Health Organization declared mpox (formerly monkeypox) a Public Health Emergency of International Concern in July 2022. Aotearoa New Zealand has reported cases of mpox since July, with reports of locally acquired cases since October 2022. The 2022 global mpox outbreak highlights many features of the illness not previously described, including at-risk populations, mode of transmission, atypical clinical features, and complications. It is important that all clinicians are familiar with the variety of clinical manifestations, as patients may present to different healthcare providers, and taking lessons from the HIV pandemic, that all patients are managed without stigma or discrimination. There have been numerous publications since the outbreak began. Our narrative clinical review attempts to bring together the current clinical evidence for the New Zealand clinician.
36,796,227
Awareness of chemsex, pre-exposure prophylaxis, and sexual behavior in primary health care in Spain.
To describe the degree of knowledge of primary care professionals about the practice of chemsex, its potential side effects and pre-exposure prophylaxis against HIV (PrEP). Observational, descriptive, cross-sectional, observational study using an online survey aimed at primary care professionals. The survey consisted of 25 questions on (i)sociodemographic data (ii)performance of sexual interview in the consultation (iii) level of knowledge about the use of chemsex and its complications (iv)degree of knowledge about PrEP, and (v)training needs of professionals. The survey was designed in ArgisSurvey123 and distributed through SEMERGEN via distribution list and corporate mail. One hundred and fifty-seven responses were obtained during the survey distribution period (February-March 2022). The majority of respondents were women (71.8%). The percentage of sexual interviewing in routine clinical practice was low. Most respondents (73%) had heard of chemsex, but were not comfortable with their knowledge of the pharmacokinetic properties of the main drugs used in this practice. 52.3% of respondents claimed to have no knowledge of PrEP. Updating and responding to the training needs of professionals regarding chemsex and PrEP is essential to ensure the care and quality of care for our patients.
36,796,006
Medical Care of people living with HIV in the Instituto Mexicano del Seguro Social.
Infection by the human immunodeficiency virus (HIV) is apublic health problem worldwide, however, the incidence has remained relatively stable. In Mexico, around 10,000 new cases are reported each year. The Instituto Mexicano del Seguro Social (IMSS) has been a pioneer in the care of people living with HIV (PLWHA), gradually incorporating the different antiretroviral drugs (ARV). The first ARV used at the institutional level was zidovudine, in the 1990s, and later other agents were incorporated, such as protease inhibitors, drugs from the group of non-nucleoside analogs, and integrase inhibitors. In 2020, the migration to ARV schemes coformulated in a single tablet based on integrase inhibitors, which constitute a highly effective option and timely supply of drugs has been achieved in 99% of the population. In the aspect of prevention, the IMSS has also been a pioneer by being the first institution to implement HIV pre-exposure prophylaxis in 2021 at the national level and since 2022 universal post-exposure prophylaxis is available. The IMSS continues to be at the forefront incorporating the use of different management tools and instruments for the benefit of the population living with HIV. This document summarizes the history of HIV in the IMSS from the beginning of the epidemic to the present time. La infección por el virus de la inmunodeficiencia humana (VIH) es un problema de salud pública a nivel mundial, sin embargo, la incidencia ha permanecido relativamente estable. En México se informa de alrededor de 10,000 casos nuevos al año. El Instituto Mexicano del Seguro Social (IMSS) ha sido pionero en la atención a las personas que viven con el VIH (PVV), incorporando paulatinamente los diferentes medicamentos antirretrovirales (ARV). El primer ARV utilizado a nivel institucional fue la zidovudina, en la década de los noventa, y posteriormente fueron incorporados otros agentes como los inhibidores de la proteasa, los medicamentos del grupo de los análogos no nucleósidos y los inhibidores de la integrasa. En el año 2020 ocurrió la migración a esquemas de ARV coformulados en una sola tableta a base de inhibidores de la integrasa, que constituyen una opción de alta eficacia y se ha logrado el surtimiento oportuno de los fármacos en el 99% de la población. En el aspecto de la prevención, el IMSS también ha sido pionero al ser la primera institución en implementar la profilaxis preexposición de VIH en el año 2021 a nivel nacional y desde el año 2022 se dispone de la profilaxis postexposición universal. El IMSS continúa a la vanguardia incorporando el uso de diferentes herramientas e instrumentos de gestión para beneficio de la población que vive con el VIH. En el presente documento se sintetiza la historia del VIH en el IMSS desde los inicios de la epidemia hasta el momento actual.
36,795,989
Cancer-Related Stigma in Malawi Narratives of Cancer Survivors.
Stigma is an impediment across the cancer care continuum, leading to delayed presentation to care, elevated morbidity and mortality, and reduced quality of life. The goal of this study was to qualitatively examine the drivers, manifestations, and impacts of cancer-related stigma among individuals who received cancer treatment in Malawi, and to identify opportunities to address stigma. Individuals who had completed treatment for lymphoma (n 20) or breast cancer (n 9) were recruited from observational cancer cohorts in Lilongwe, Malawi. Interviews explored the individuals cancer journey, from first symptoms through diagnosis, treatment, and recovery. Interviews were audio-recorded and translated from Chichewa to English. Data were coded for content related to stigma, and thematically analyzed to describe the drivers, manifestations, and impacts of stigma along the cancer journey. Drivers of cancer stigma included beliefs of cancer origin (cancer as infectious cancer as a marker of HIV cancer due to bewitchment), perceived changes in the individual with cancer (loss of socialeconomic role physical changes), and expectations about the individuals future (cancer as death sentence). Cancer stigma manifested through gossip, isolation, and courtesy stigma toward family members. The impacts of cancer stigma included mental health distress, impediments to care engagement, lack of cancer disclosure, and self-isolation. Participants suggested the following programmatic needs community education about cancer counseling in health facilities and peer support from cancer survivors. The results highlight multifactorial drivers, manifestations, and impacts of cancer-related stigma in Malawi, which may affect success of cancer screening and treatment programs. There is a clear need for multilevel interventions to improve community attitudes toward people with cancer, and to support individuals along the continuum of cancer care.
36,795,933
HIVAIDS infection in critical care epidemiological profile and risk factors for mortality in a Colombian cohort.
Outcomes of human immunodeficiency virus (HIV) infected patients admitted to intensive care units (ICU) have improved with antiretroviral therapy (ART). However, whether the outcomes have improved in low- and middle-income countries, paralleling those of high-income countries is unknown. The objective of this study was to describe a cohort of HIV-infected patients admitted to ICU in a middle-income country and identify the risk factors associated with mortality. A cohort study of HIV-infected patients admitted to five ICUs in Medellín, Colombia, between 2009 and 2014 was done. The association of demographic, clinical and laboratory variables with mortality was analyzed using a Poisson regression model with random effects. During this time period, 472 admissions of 453 HIV-infected patients were included. Indications for ICU admission were respiratory failure (57%), sepsisseptic shock (30%) and central nervous system (CNS) compromise (27%). Opportunistic infections (OI) explained 80% of ICU admissions. Mortality rate was 49%. Factors associated with mortality included hematological malignancies, CNS compromise, respiratory failure, and APACHE II score ≥ 20. Despite advances in HIV care in the ART era, half of HIV-infected patients admitted to the ICU died. This elevated mortality was associated to underlying disease severity (respiratory failure and APACHE II score ≥ 20), and host conditions (hematological malignancies, admission for CNS compromise). Despite the high prevalence of OIs in this cohort, mortality was not directly associated to OIs.
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Clinical and microbiological patterns in critically ill patients with catheter-associated UTI A report from Iran.
Catheter-associated urinary tract infections (CAUTIs) are among the most common nosocomial infections with different clinical and microbiological characteristics. We studied these characteristics in critically ill patients. This research was a cross-sectional study conducted on intensive care unit (ICU) patients with CAUTI. Patients demographic and clinical information and laboratory data, including causative microorganisms and antibiotic susceptibility tests, were recorded and analyzed. Finally, the differences between the patients who survived and died were compared. After reviewing 353 ICU cases, 80 patients with CAUTI were finally included in the study. The mean age was 55.9 ± 19.1 years, 43.7% were male and 56.3% were female. The mean length of infection development since hospitalisation and hospital stay were 14.7 (3-90) and 27.8 (5-98) days, respectively. The most common symptom was fever (80%). The microbiological identification showed that the most isolated microorganisms were Multidrug-resistant (MDR) Enterobacteriaceae (75%), Pseudomonas aeruginosa (8.8%), Gram-positive uropathogens (8.8%) and Acinetobacter baumannii (5%). Fifteen patients (18.8%) died among whom infections with A. baumannii (75%) and P. aeruginosa (57.1%) were associated with more death (p 0.005). Although A. baumannii and P. aeruginosa can be the most important pathogens for death, MDR Enterobacteriaceae are still a serious concern as causes of CAUTIs.
36,795,919
Treponema pallidum infection rate in patients attending the general hospital of Benguela, Angola.
The objectives of this study were to estimate the rate of infection by Treponema pallidum and co-infection with Human Immunodeficiency Virus (HIV) in individuals attending the General Hospital of Benguela (GHB), Angola, to verify the Rapid Plasma Reagin (RPR) test performance for its diagnosis when compared with other RPR tests, and to compare a rapid treponemal test with the Treponema pallidum hemagglutination assay (TPHA). This is a cross-sectional study carried out between August 2016 and January 2017, at the GHB, 546 individuals attending the emergency room, the outpatient service or hospitalized at the GHB were included. All the samples were tested at the GHB with the routine hospital RPR test and a rapid treponemal test. The samples were then transported to the Institute of Hygiene and Tropical Medicine (IHMT) where RPR testing and TPHA testing were performed. The rate of T. pallidum active infection, demonstrated by a reactive RPR and TPHA result, was 2.9%, of which 81.2% corresponded to indeterminate latent syphilis and 18.8% to secondary syphilis. HIV co-infection was detected in 62.5% of individuals diagnosed with syphilis. Past infection, defined as a non-reactive RPR and reactive TPHA test, was diagnosed in 4.1% of individuals. The high rate of syphilisHIV co-infection emphasizes the urgent requirement for adequate sexually transmitted infections (STIs) screening, prevention and treatment programs. In addition, implementation of quality control measures within RPR testing protocols at GHB are needed, including training for laboratory personnel, adequate equipment and introduction of other rapid testing.
36,795,795
Joint modeling of longitudinal changes of blood pressure and time to remission of hypertensive patients receiving treatment Bayesian approach.
Hypertension is a widespread condition when the bloods force on the artery walls is extremely high to develop adverse health effects. This paper aimed to jointly model the longitudinal change of blood pressures (systolic and diastolic) and time to the first remission of hypertensive outpatients receiving treatment. A retrospective study design was used to collect appropriate data on longitudinal changes in blood pressure and time-to-event from the medical charts of 301 hypertensive outpatients under follow-up at Felege Hiwot referral hospital, Ethiopia. The data exploration was done using summary statistics measures, individual profile plots, Kaplan-Meier plots, and log-rank tests. To get wide-ranging information about the progression, joint multivariate models were employed. A total of 301 hypertensive patients who take treatment was taken from Felege Hiwot referral hospital recorded between Sep. 2018 to Feb. 2021. Of this 153 (50.8%) were male, and 124 (49.2%) were residents from rural areas. About 83(27.6%), 58 (19.3%), 82 (27.2%), and 25 (8.3%) have a history of diabetes mellitus, cardiovascular disease, stroke, and HIV respectively. The median time of hypertensive patients to have first remission time was 11 months. The hazard of the patients first remission time for males was 0.63 times less likely than the hazard for females. The time to attain the first remission for patients who had a history of diabetes mellitus was 46% lower than for those who had no history of diabetes mellitus. Blood pressure dynamics significantly affect the time to the first remission of hypertensive outpatients receiving treatment. The patients who had a good follow-up, lower BUN, lower serum calcium, lower serum sodium, lower hemoglobin, and take the treatment enalapril showed an opportunity in decreasing their blood pressure. This compels patients to experience the first remission early. Besides, age, patients history of diabetes, patients history of cardiovascular disease, and treatment type were the joint determinant factors for the longitudinal change of BP and the first remission time. The Bayesian joint model approach provides specific dynamic predictions, wide-ranging information about the disease transitions, and better knowledge of disease etiology.
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High PrEP uptake and objective longitudinal adherence among HIV-exposed women with personal or partner plans for pregnancy in rural Uganda A cohort study.
In Uganda, fertility rates and adult HIV prevalence are high, and many women conceive with partners living with HIV. Pre-exposure prophylaxis (PrEP) reduces HIV acquisition for women and, therefore, infants. We developed the Healthy Families-PrEP intervention to support PrEP use as part of HIV prevention during periconception and pregnancy periods. We conducted a longitudinal cohort study to evaluate oral PrEP use among women participating in the intervention. We enrolled HIV-negative women with plans for pregnancy with a partner living, or thought to be living, with HIV (2017 to 2020) to evaluate PrEP use among women participating in the Healthy Families-PrEP intervention. Quarterly study visits through 9 months included HIV and pregnancy testing and HIV prevention counseling. PrEP was provided in electronic pillboxes, providing the primary adherence measure (high adherence when pillbox was opened ≥80% of days). Enrollment questionnaires assessed factors associated with PrEP use. Plasma tenofovir (TFV) and intraerythrocytic TFV-diphosphate (TFV-DP) concentrations were determined quarterly for women who acquired HIV and a randomly selected subset of those who did not concentrations TFV ≥40 ngmL and TFV-DP ≥600 fmolpunch were categorized as high. Women who became pregnant were initially exited from the cohort by design from April 2019, women with incident pregnancy remained in the study with quarterly follow-up until pregnancy outcome. Primary outcomes included (1) PrEP uptake (proportion who initiated PrEP) and (2) PrEP adherence (proportion of days with pillbox openings during the first 3 months following PrEP initiation). We used univariable and multivariable-adjusted linear regression to evaluate baseline predictors selected based on our conceptual framework of mean adherence over 3 months. We also assessed mean monthly adherence over 9 months of follow-up and during pregnancy. We enrolled 131 women with mean age 28.7 years (95% CI 27.8 to 29.5). Ninety-seven (74%) reported a partner with HIV and 79 (60%) reported condomless sex. Most women (N 118 90%) initiated PrEP. Mean electronic adherence during the 3 months following initiation was 87% (95% CI 83%, 90%). No covariates were associated with 3-month pill-taking behavior. Concentrations of plasma TFV and TFV-DP were high among 66% and 47%, 56% and 41%, and 45% and 45% at months 3, 6, and 9, respectively. We observed 53 pregnancies among 131 women (1-year cumulative incidence 53% 95% CI 43%, 62%) and 1 HIV-seroconversion in a non-pregnant woman. Mean pillcap adherence for PrEP users with pregnancy follow-up (N 17) was 98% (95% CI 97%, 99%). Study design limitations include lack of a control group. Women in Uganda with PrEP indications and planning for pregnancy chose to use PrEP. By electronic pillcap, most were able to sustain high adherence to daily oral PrEP prior to and during pregnancy. Differences in adherence measures highlight challenges with adherence assessment serial measures of TFV-DP in whole blood suggest 41% to 47% of women took sufficient periconception PrEP to prevent HIV. These data suggest that women planning for and with pregnancy should be prioritized for PrEP implementation, particularly in settings with high fertility rates and generalized HIV epidemics. Future iterations of this work should compare the outcomes to current standard of care. ClinicalTrials.gov Identifier NCT03832530 httpsclinicaltrials.govct2showNCT03832530termlynnmatthewscondhivcntryUGdraw2rank1.
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HIV-1 prehairpin intermediate inhibitors show efficacy independent of neutralization tier.
HIV-1 strains are categorized into one of three neutralization tiers based on the relative ease by which they are neutralized by plasma from HIV-1-infected donors not on antiretroviral therapy tier-1 strains are particularly sensitive to neutralization while tier-2 and tier-3 strains are increasingly difficult to neutralize. Most broadly neutralizing antibodies (bnAbs) previously described target the native prefusion conformation of HIV-1 Envelope (Env), but the relevance of the tiered categories for inhibitors targeting another Env conformation, the prehairpin intermediate, is not well understood. Here, we show that two inhibitors targeting distinct highly conserved regions of the prehairpin intermediate have strikingly consistent neutralization potencies (within 100-fold for a given inhibitor) against strains in all three neutralization tiers of HIV-1 in contrast, best-in-class bnAbs targeting diverse Env epitopes vary by more than 10,000-fold in potency against these strains. Our results indicate that antisera-based HIV-1 neutralization tiers are not relevant for inhibitors targeting the prehairpin intermediate and highlight the potential for therapies and vaccine efforts targeting this conformation.
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Doing more with less The use of non-invasive ventilatory support in a resource-limited setting.
Bubble CPAP (bCPAP), a non-invasive ventilation modality, has emerged as an intervention that is able to reduce pneumonia-related mortality in children in low resourced settings. Our study primarily aimed to describe a cohort of children who were started on CPAP in the Medical Emergency Unit (MEU) of Red Cross War Memorial Childrens Hospital 2016-2018. A retrospective review of a randomly selected sample of paper-based folders was conducted. Children started on bCPAP at MEU were eligible for inclusion. Demographic and clinical data, management, and outcomes regarding admission to PICU, need for invasive ventilation and mortality were documented. Descriptive statistical data were generated for all relevant variables. Percentages depicted frequencies of categorical data while medians with interquartile ranges (IQR) were used to summarise continuous data. Of 500 children started on bCPAP, 266 (53%) were male their median age was 3.7 (IQR 1.7-11.3) months and 169 (34%) were moderately to severely underweight-for-age. There were 12 (2%) HIV-infected children 403 (81%) had received appropriate immunisations for their age and 119 (24%) were exposed to tobacco smoke at home. The five most common primary reasons for admission were acute respiratory illness, acute gastroenteritis, congestive cardiac failure, sepsis and seizures. Most children, 409 (82%), had no underlying medical condition. Most children, 411 (82%), were managed in high care areas of the general medical wards while 126 (25%) went to PICU. The median time on CPAP was 1.7 (IQR 0.9-2.8) days. The median hospitalisation time was 6 (IQR 4-9) days. Overall, 38 (8%) children required invasive ventilatory support. Overall, 12 (2%) children with a median age of 7.5 (IQR 0.7-14.5) months died, six of whom had an underlying medical condition. Seventy-five percent of children initiated on bCPAP did not require PICU admission. This form of non-invasive ventilatory support should be considered more widely in the context of limited access to paediatric intensive care units in other African settings.
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Drivers of disparities in stage at diagnosis among women with breast cancer South African breast cancers and HIV outcomes cohort.
In low- and middle-income countries (LMICs), advanced-stage diagnosis of breast cancer (BC) is common, and this contributes to poor survival. Understanding the determinants of the stage at diagnosis will aid in designing interventions to downstage disease and improve survival from BC in LMICs. Within the South African Breast Cancers and HIV Outcomes (SABCHO) cohort, we examined factors affecting the stage at diagnosis of histologically confirmed invasive breast cancer at five tertiary hospitals in South Africa (SA). The stage was assessed clinically. To examine the associations of the modifiable health system, socio-economichousehold and non-modifiable individual factors, hierarchical multivariable logistic regression with odds of late-stage at diagnosis (stage III-IV), was used. The majority (59%) of the included 3497 women were diagnosed with late-stage BC disease. The effect of health system-level factors on late-stage BC diagnosis was consistent and significant even when adjusted for both socio-economic- and individual-level factors. Women diagnosed in a tertiary hospital that predominantly serves a rural population were 3 times (OR 2.89 (95% CI 1.40-5.97) as likely to be associated with late-stage BC diagnosis when compared to those diagnosed at a hospital that predominantly serves an urban population. Taking more than 3 months from identifying the BC problem to the first health system entry (OR 1.66 (95% CI 1.38-2.00)), and having luminal B (OR 1.49 (95% CI 1.19-1.87)) or HER2-enriched (OR 1.64 (95% CI 1.16-2.32)) molecular subtype as compared to luminal A, were associated with a late-stage diagnosis. Whilst having a higher socio-economic level (a wealth index of 5) reduced the probability of late-stage BC at diagnosis, (OR 0.64 (95% CI 0.47-0.85)). Advanced-stage diagnosis of BC among women in SA who access health services through the public health system was associated with both modifiable health system-level factors and non-modifiable individual-level factors. These may be considered as elements in interventions to reduce the time to diagnosis of breast cancer in women.
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Implementing social interventions in primary care in Canada A qualitative exploration of lessons learned from leaders in the field.
Primary health care providers and practices are increasingly instituting direct interventions into social determinants of health and health inequities, but experiences of the leaders in these initiatives remain largely unexamined. Sixteen semi-structured interviews with Canadian primary care leaders in developing and implementing social interventions were conducted to assess barriers, keys to success, and lessons learned from their work. Participants focused on practical approaches to establishing and maintaining social intervention programs and our analysis pointed to six major themes. A deep understanding of community needs, through data and client stories, forms a foundation for program development. Improving access to care is essential to ensuring programs reach those most marginalized. Client care spaces must be made safe as a first step to engagement. Intervention programs are strengthened by the involvement of patients, community members, health team staff, and partner agencies in their design. The impact and sustainability of these programs is enhanced by implementation partnerships with community members, community organizations, health team members, and government. Health providers and teams are more likely to assimilate simple, practical tools into practice. Finally, institutional change is key to establishing successful programs. Creativity, persistence, partnership, a deep understanding of community and individual social needs, and a willingness to overcome barriers underlie the implementation of successful social intervention programs in primary health care settings.
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Microbiological diagnosis and mortality of tuberculosis meningitis Systematic review and meta-analysis.
Tuberculosis (TB) which is caused by Mycobacterium tuberculosis poses a significant public health global treat. Tuberculosis meningitis (TBM) accounts for approximately 1% of all active TB cases. The diagnosis of Tuberculosis meningitis is notably difficult due to its rapid onset, nonspecific symptoms, and the difficulty of detecting Mycobacterium tuberculosis in cerebrospinal fluid (CSF). In 2019, 78,200 adults died of TB meningitis. This study aimed to assess the microbiological diagnosis TB meningitis using CSF and estimated the risk of death from TBM. Relevant electronic databases and gray literature sources were searched for studies that reported presumed TBM patients. The quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal tools designed for prevalence studies. Data were summarized using Microsoft excel ver 16. The proportion of culture confirmed TBM, prevalence of drug resistance and risk of death were calculated using the random-effect model. Stata version 16.0 was used perform the statistical analysis. Moreover, subgroup analysis was conducted. After systematic searching and quality assessment, 31 studies were included in the final analysis. Ninety percent of the included studies were retrospective studies in design. The overall pooled estimates of CSF culture positive TBM was 29.72% (95% CI 21.42-38.02). The pooled prevalence of MDR-TB among culture positive TBM cases was 5.19% (95% CI 3.12-7.25). While, the proportion of INH mono-resistance was 9.37% (95% CI 7.03-11.71). The pooled estimate of case fatality rate among confirmed TBM cases was 20.42% (95%CI 14.81-26.03). Based on sub group analysis, the pooled case fatality rate among HIV positive and HIV negative TBM individuals was 53.39% (95%CI 40.55-66.24) and 21.65% (95%CI4.27-39.03) respectively. Definite diagnosis of TBM still remains global treat. Microbiological confirmation of TBM is not always achievable. Early microbiological confirmation of TBM has great importance to reduce mortality. There was high rate of MDR-TB among confirmed TBM patients. All TB meningitis isolates should be cultured and drug susceptibility tested using standard techniques.
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Realizing the Promise of Dolutegravir in Effectively Treating Children and Adolescents Living With HIV in Real-world Settings in 6 Countries in Eastern and Southern Africa.
Despite encouraging results from clinical trials and in high-income countries, large-scale data on the effectiveness and safety of dolutegravir (DTG) in children and adolescents living with HIV (CALHIV) are lacking in low- and middle-income countries (LMICs). Retrospective analysis was performed among CALHIV 0-19 years old and weighing greater than or equal to 20 kg who received DTG from 2017 to 2020 at sites in Botswana, Eswatini, Lesotho, Malawi, Tanzania and Uganda to determine effectiveness, safety and predictors of viral load suppression (VLS) among CALHIV using DTG, including through single drug substitutions (SDS). Among 9419 CALHIV using DTG, 7898 had a documented post-DTG VL, and VLS post-DTG was 93.4% (73787898). VLS for antiretroviral therapy (ART) initiations was 92.4% (246263), and VLS was maintained for the ART-experienced 92.9% (70267560) pre- vs. 93.5% (70717560) post-DTG P 0.14). Among previously unsuppressed, 79.8% (426534) achieved VLS with DTG. Only 5 patients reported a Grade 3 or 4 adverse event (0.057 per 100 patient-years) requiring DTG discontinuation. History of protease inhibitor-based ART odds ratio (OR) 1.53 95% confidence interval (CI) 1.16-2.03, care in Tanzania (OR 5.45 95% CI 3.41-8.70), and being 15-19 years old (OR 1.31 95% CI 1.03-1.65) were associated with gain of VLS post-DTG. Predictors of VLS on DTG included VLS before DTG (OR 3.87 95% CI 3.03-4.95) and using the once-daily, single tab tenofovir-lamivudine-DTG regimen (OR 1.78 95% CI 1.43-2.22). SDS maintained VLS 95.9% (20322120) pre- vs. 95.0% (20142120) post-SDS with DTG P 0.19, and 83.0% (7388) of unsuppressed gained VLS using SDS with DTG. We found DTG to be highly effective and safe within our cohort of CALHIV in LMICs. These findings can empower clinicians to prescribe DTG confidently to eligible CALHIV.
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The Evolving Pediatric HIV Epidemic in Rural Southern Zambia The Beneficial Impact of Advances in Prevention and Treatment at a District Hospital From 2007 to 2019.
Remarkable progress has been made in expanding access to services addressing the pediatric HIV epidemic, including programs to prevent mother-to-child transmission, early diagnosis and treatment for children living with HIV. Few long-term data are available from rural sub-Saharan Africa to assess implementation and impact of national guidelines. Results from 3 cross-sectional studies and 1 cohort study conducted at Macha Hospital in Southern Province, Zambia from 2007 to 2019 were summarized. For infant diagnosis, maternal antiretroviral treatment, infant test results and turnaround times for results were evaluated by year. For pediatric HIV care, the number and age of children initiating care and treatment, and treatment outcomes within 12 months were evaluated by year. Receipt of maternal combination antiretroviral treatment increased from 51.6% in 2010-2012 to 93.4% in 2019, and the proportion of infants testing positive decreased from 12.4% to 4.0%. Turnaround times for results returning to clinic varied but were shorter when labs consistently used a text messaging system. The proportion of mothers receiving results was higher when a text message intervention was piloted. The number of children living with HIV enrolled into care and the proportion initiating treatment with severe immunosuppression and dying within 12 months decreased over time. These studies demonstrate the long-term beneficial impact of implementing a strong HIV prevention and treatment program. While expansion and decentralization brought challenges, the program succeeded in decreasing the rate of mother-to-child transmission and ensuring that children living with HIV benefit from access to life-saving treatment.
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Highly Active Antiretroviral Therapy in an Extremely Low Birth Weight Newborn With in Utero Transmission of HIV.
The management of perinatal HIV infection in preterm infants is hampered by the lack of evidence informing optimal antiretroviral treatment for these vulnerable newborns. We present a case of an extremely preterm infant with HIV infection treated immediately with a 3-drug antiretroviral regimen and achieving stable suppression of HIV plasma viral load.
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Risk and Protective Profile of Men Who Have Sex With Men Using Mobile Voluntary HIV Counseling and Testing Latent Class Analysis.
Mobile voluntary counseling and testing (VCT) for HIV has been carried out to improve the targeting of at-risk populations and HIV case detection for men who have sex with men (MSM). However, the HIV-positive detection rate using this screening strategy has declined in recent years. This may imply unknown changes in risk-taking and protective features jointly influencing the testing results. These changing patterns in this key population remain unexplored. The aim of this study was to identify the nuanced group classification of MSM who underwent mobile VCT using latent class analysis (LCA), and to compare the difference in characteristics and testing results between subgroups. A cross-sectional research design and purposive sampling were applied between May 21, 2019, and December 31, 2019. Participants were recruited by a well-trained research assistant through social networking platforms, including the most popular instant messenger app Line, geosocial network apps dedicated to MSM, and online communities. Mobile VCT was provided to participants at an assigned time and place. Demographic characteristics and risk-taking and protective features of the MSM were collected via online questionnaires. LCA was used to identify discrete subgroups based on four risk-taking indicators-multiple sexual partners (MSP), unprotected anal intercourse (UAI), recreational drug use within the past 3 months, and history of sexually transmitted diseases-and three protective indicators-experience of postexposure prophylaxis, preexposure prophylaxis use, and regular HIV testing. Overall, 1018 participants (mean age 30.17, SD 7.29 years) were included. A three-class model provided the best fit. Classes 1, 2, and 3 corresponded to the highest risk (n175, 17.19%), highest protection (n121, 11.89%), and low risk and low protection (n722, 70.92%), respectively. Compared to those of class 3, class 1 participants were more likely to have MSP and UAI within the past 3 months, to be ≥40 years of age (odds ratio OR 2.197, 95% CI 1.357-3.558 P.001), to have HIV-positive results (OR 6.47, 95% CI 2.272-18.482 P<.001), and a CD4 count ≤349μL (OR 17.50, 95% CI 1.223-250.357 P.04). Class 2 participants were more likely to adopt biomedical preventions and have marital experience (OR 2.55, 95% CI 1.033-6.277 P.04). LCA helped derive a classification of risk-taking and protection subgroups among MSM who underwent mobile VCT. These results may inform policies for simplifying the prescreening assessment and more precisely recognizing those who have higher probabilities of risk-taking features but remain undiagnosed targets, including MSM engaging in MSP and UAI within the past 3 months and those ≥40 years old. These results could be applied to tailor HIV prevention and testing programs.
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Clinic-Integrated Smartphone App (JomPrEP) to Improve Uptake of HIV Testing and Pre-exposure Prophylaxis Among Men Who Have Sex With Men in Malaysia Mixed Methods Evaluation of Usability and Acceptability.
HIV disproportionately affects men who have sex with men (MSM). In Malaysia, where stigma and discrimination toward MSM are high, including in health care settings, mobile health (mHealth) platforms have the potential to open new frontiers in HIV prevention. We developed an innovative, clinic-integrated smartphone app called JomPrEP, which provides a virtual platform for Malaysian MSM to engage in HIV prevention services. In collaboration with the local clinics in Malaysia, JomPrEP offers a range of HIV prevention (ie, HIV testing and pre-exposure prophylaxis PrEP) and other support services (eg, referral to mental health support) without having to interface face to face with clinicians. This study evaluated the usability and acceptability of JomPrEP to deliver HIV prevention services for MSM in Malaysia. In total, 50 PrEP-naive MSM without HIV in Greater Kuala Lumpur, Malaysia, were recruited between March and April 2022. Participants used JomPrEP for a month and completed a postuse survey. The usability of the app and its features were assessed using self-report and objective measures (eg, app analytics, clinic dashboard). Acceptability was evaluated using the System Usability Scale (SUS). The participants mean age was 27.9 (SD 5.3) years. Participants used JomPrEP for an average of 8 (SD 5.0) times during 30 days of testing, with each session lasting an average of 28 (SD 38.9) minutes. Of the 50 participants, 42 (84%) ordered an HIV self-testing (HIVST) kit using the app, of whom 18 (42%) ordered an HIVST more than once. Almost all participants (4650, 92%) initiated PrEP using the app (same-day PrEP initiation 3046, 65%) of these, 1646 (35%) participants chose PrEP e-consultation via the app (vs in-person consultation). Regarding PrEP dispensing, 1846 (39%) participants chose to receive their PrEP via mail delivery (vs pharmacy pickup). The app was rated as having high acceptability with a mean score of 73.8 (SD 10.1) on the SUS. JomPrEP was found to be a highly feasible and acceptable tool for MSM in Malaysia to access HIV prevention services quickly and conveniently. A broader, randomized controlled trial is warranted to evaluate its efficacy on HIV prevention outcomes among MSM in Malaysia. ClinicalTrials.gov NCT05052411 httpsclinicaltrials.govct2showNCT05052411. RR2-10.219643318.
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The use of TNF-α antagonists in tuberculosis to control severe paradoxical reaction or immune reconstitution inflammatory syndrome a case series and literature review.
Paradoxical reaction (PR) and immune reconstitution inflammatory syndrome (IRIS) are common complications of tuberculosis treatment. Corticosteroids are first-line treatment for severe PR or IRIS, particularly neurological. We report four cases of severe PR or IRIS during tuberculosis treatment who required TNF-α antagonists, and identified 20 additional cases through literature review. They were 14 women and 10 men, with a median age of 36 years (interquartile range, 28-52). Twelve were immunocompromised before tuberculosis untreated HIV infection (n6), or immunosuppressive treatment (TNF-α antagonists, n5 tacrolimus, n1). Tuberculosis was mostly neuromeningeal (n15), pulmonary (n10), lymph node (n6), and miliary (n6), multi-susceptible in 23 cases. PR or IRIS started after a median time of 6 weeks (IQR, 4-9) following anti-tuberculosis treatment start, and consisted primarily of tuberculomas (n11), cerebral vasculitis (n8), and lymphadenitis (n6). First-line treatment of PR or IRIS was high-dose corticosteroids in 23 cases. TNF-α antagonists were used as salvage treatment in all cases, with infliximab (n17), thalidomide (n6), and adalimumab (n3). All patients improved, but 6 had neurological sequelae, and 4 had TNF-α antagonist-related severe adverse events. TNF-α antagonists are safe and effective as salvage or corticosteroid-sparing therapeutic for severe PR or IRIS during tuberculosis treatment.
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Successful treatment of HIV-associated progressive multifocal leukoencephalopathy (PML) with mirtazapine, mefloquine, and IVIG combination therapy a case report.
Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system caused by reactivation of the polyomavirus JC (JCV). Human immunodeficiency virus (HIV) infection is one of the leading causes of PML which has high morbidity and mortality due to the lack of a proven standard treatment. We found clinical and radiological improvement with the combination of high-dose methylprednisolone, mirtazapine, mefloquine, and IVIG in our patient who presented with neurological symptoms and had diagnosed concurrent acquired immunodeficiency syndrome (AIDS) and PML. To our knowledge, our case is the first HIV-associated PML which responded to this combination therapy.
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Does the rapid initiation of antiretroviral therapy at HIV diagnosis impact virological response in a real-life setting A single-centre experience in Northern Italy.
Rapid initiation of antiretroviral therapy (ART) has been proven efficacious and safe, but more investigations are needed to define feasibility of rapid ART approach in real-life settings.We conducted a retrospective, observational study on newly HIVdiagnosed patients referred to our Infectious Diseases Department from September 1st, 2015, to July 31st, 2019. According to the timing of ART initiation, we distinguished 3 groups of patients (rapid, intermediate and late group) and represented the trend of virological response during a 400-days-period. The hazard ratios of each predictor on viral suppression were estimated through the Cox proportional hazard model.The median time from HIV diagnosis to the first medical referral was 15 days and the median time from the first care access to therapy start was 24 days. Among patients, 37.6% started ART within 7 days, 20.6% between 8 and 30 days, and 41.8% after 30 days. Longer time to ART start and higher baseline viral load were associated with a lower probability of viral suppression. After one year, all groups showed a high viral suppression rate (99%). In a high-income setting the rapid ART approach seems useful to accelerate viral suppression which is great over time regardless of ART initiation timing.
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Network-based multi-omics integration reveals metabolic at-risk profile within treated HIV-infection.
Multiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PLWH). Still, a systematic and in-depth characterization of metabolic risk profile during successful long-term treatment is lacking. Here, we used multi-omics (plasma lipidomic, metabolomic, and fecal 16S microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PLWH. Through network analysis and similarity network fusion (SNF), we identified three groups of PLWH (SNF-1 to 3) healthy (HC)-like (SNF-1), mild at-risk (SNF-3), and severe at-risk (SNF-2). The PLWH in the SNF-2 (45%) had a severe at-risk metabolic profile with increased visceral adipose tissue, BMI, higher incidence of metabolic syndrome (MetS), and increased di- and triglycerides despite having higher CD4
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Disclosure of HIV status and associated clinical outcomes of children and adolescents living with HIV in Asia.
Disclosure of HIV status is an important part of pediatric care. We studied disclosure and clinical outcomes in a multi-country Asian cohort of children and adolescents with HIV. Those 6-19 years of age who initiated combination antiretroviral therapy (cART) between 2008 and 2018, and who had at least one follow-up clinic visit were included. Data up to December 2019 were analyzed. Cox and competing risk regression analyses were used to assess the effect of disclosure on disease progression (WHO clinical stage 3 or 4), loss to follow-up (LTFU > 12 months), and death. Of 1913 children and adolescents (48% female median IQR age 11.5 9.2-14.7 years at last clinic visit), 795 (42%) were disclosed to about their HIV status at a median age of 12.9 years (IQR 11.8-14.1). During follow-up, 207 (11%) experienced disease progression, 75 (3.9%) were LTFU, and 59 (3.1%) died. There were lower hazards of disease progression (adjusted hazard ratio aHR 0.43 0.28-0.66) and death (aHR 0.36 0.17-0.79) for those disclosed to compared with those who were not. Disclosure and its appropriate implementation should be promoted in pediatric HIV clinics in resource-limited settings.
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Asymptomatic Carriage Rate, Multidrug Resistance Level, and Associated Risk Factors of Enterococcus in Clinical Samples among HIV-Positive Patients Attending at Debre Birhan Comprehensive Specialized Hospital, North Showa, Ethiopia.
Enterococci are facultative anaerobic, Gram-positive bacteria found in pairs and short chains that exist as normal microflora both human and animal. Enterococci have become a substantial source of nosocomial infections in immunocompromised patients, such as urinary tract infection (UTI), bacteremia, endocarditis, and wound infection. Earlier antibiotic therapy, length of hospital stays, and length of earlier vancomycin treatment, surgical wards, or intensive care units are all risk factors. Additionally, the presence of coinfections such as diabetes and renal failure and the presence of a urinary catheter were aggravated factors to develop infections. Data on the prevalence, antimicrobial susceptibility patterns, and associated factors of enterococcal infection among HIV-positive patients are scarce in Ethiopia. To determine the asymptomatic carriage rate, multidrug resistance pattern, and risk factors of enterococci in clinical samples among HIV-positive patients attending at Debre Birhan Comprehensive Specialized Hospital, North Showa, Ethiopia. A hospital-based cross-sectional study was conducted from May to August 2021, at Debre Birhan Comprehensive Specialized Hospital. To obtain sociodemographic data and possible associated factors of enterococcal infections, a pretested structured questionnaire was utilized. During the study period, clinical samples such as urine, blood, swabs, and other bodily fluids from participants sent to the bacteriology section for cultures were included. The study comprised a total of 384 HIV-positive patients. Enterococci were identified and confirmed using bile esculin azide agar (BEAA), Gram stain, catalase response, growth in broth containing 6.5% NaCl, and growth in BHI broth at 45°C. Data were entered and analyzed using SPSS version 25. The overall asymptomatic carriage rate of enterococcal infection was 8.85% (34384). Urinary tract infections were the most common, followed by wounds and blood. The vast majority of the isolate was found in urine, blood, and wound and fecal, 11 (32.4%), 6 (17.6%), and 5 (14.7%), respectively. Overall, 28 (82.35%) bacterial isolates were resistant to three and more than three antimicrobial agents. Duration of hospital associated with >48-hour hospital stays (AOR 5.23, 95% C.I 3.42-24.6), previous history of catheterization (AOR 3.5, 95% C.I 5.12-44.31), WHO clinical, stage IV (AOR 1.65, 95% C.I 1.23-3.61), andCD4 count < 350(AOR 3.5, 95% C.I 5.12-44.31) (
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Pooled prevalence and determinants of antenatal care visits in countries with high maternal mortality A multi-country analysis.
Complications during pregnancy and childbirth are the leading causes of maternal and child deaths and disabilities, particularly in low- and middle-income countries. Timely and frequent antenatal care prevents these burdens by promoting existing disease treatments, vaccination, iron supplementation, and HIV counseling and testing during pregnancy. Many factors could contribute to optimal ANC utilization remaining below targets in countries with high maternal mortality. This study aimed to assess the prevalence and determinants of optimal ANC utilization by using nationally representative surveys of countries with high maternal mortality. Secondary data analysis was done using recent Demographic and Health Surveys (DHS) data of 27 countries with high maternal mortality. The multilevel binary logistic regression model was fitted to identify significantly associated factors. Variables were extracted from the individual record (IR) files of from each of the 27 countries. Adjusted odds ratios (AOR) with a 95% confidence interval (CI) and The pooled prevalence of optimal ANC utilization in countries with high maternal mortality was 55.66% (95% CI 47.48-63.85). Several determinants at the individual and community level were significantly associated with optimal ANC utilization. Mothers aged 25-34 years, mothers aged 35-49 years, mothers who had formal education, working mothers, women who are married, had media access, households of middle-wealth quintile, richest household, history of pregnancy termination, female household head, and high community education were positively associated with optimal ANC visits in countries with high maternal mortality, whereas being rural residents, unwanted pregnancy, having birth order 2-5, and birth order >5 were negatively associated. Optimal ANC utilization in countries with high maternal mortality was relatively low. Both individual-level factors and community-level factors were significantly associated with ANC utilization. Policymakers, stakeholders, and health professionals should give special attention and intervene by targeting rural residents, uneducated mothers, economically poor women, and other significant factors this study revealed.
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Inhibition of HIV-1 Protease by a Boronic Acid with High Oxidative Stability.
HIV-1 protease is an important target for pharmaceutical intervention in HIV infection. Extensive structure-based drug design led to darunavir becoming a key chemotherapeutic agent. We replaced the aniline group of darunavir with a benzoxaborolone to form BOL-darunavir. This analogue has the same potency as darunavir as an inhibitor of catalysis by wild-type HIV-1 protease and, unlike darunavir, does not lose potency as an inhibitor of the common D30N variant. Moreover, BOL-darunavir is much more stable to oxidation than is a simple phenylboronic acid analogue of darunavir. X-ray crystallography revealed an extensive network of hydrogen bonds between the enzyme and benzoxaborolone moiety, including a novel direct hydrogen bond from a main-chain nitrogen to the carbonyl oxygen of the benzoxaborolone moiety that displaces a water molecule. These data highlight the utility of benzoxaborolone as a pharmacophore.
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Prevalence of renal and bone risk factors among individuals prescribed oral pre-exposure prophylaxis for HIV.
The only available oral pre-exposure prophylaxis (PrEP) regimens approved in the United States to prevent HIV infection during the period covered by this study were emtricitabinetenofovir alafenamide (FTAF) and emtricitabinetenofovir disoproxil fumarate (FTDF). Both agents have similar efficacy, however FTAF exhibits improved bone and renal health safety endpoints over FTDF. In 2021, the United States Preventive Services Task Force recommended individuals have access to the most medically appropriate PrEP regimen. To understand the impact of these guidelines, the prevalence of risk factors to renal and bone health was evaluated among individuals prescribed oral PrEP. This prevalence study utilized the electronic health records of people prescribed oral PrEP between January 1, 2015 and February 29, 2020. Renal and bone risk factors (age, comorbidities, medication, renal function, and body mass index) were identified using International Classification of Diseases (ICD) and National Drug Code (NDC) codes. Among 40 621 individuals prescribed oral PrEP, 62% had ≥1 renal risk factor and 68% had ≥1 bone risk factor. Comorbidities were the most frequent (37%) class of renal risk factors. Concomitant medications were the most prominent (46%) class of bone-related risk factors. The high prevalence of risk factors suggests the importance of their consideration when choosing the most appropriate regimen for individuals who may benefit from PrEP.
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Optimal Control and Bifurcation Analysis of HIV Model.
In this study, a very crucial stage of HIV extinction and invisibility stages are considered and a modified mathematical model is developed to describe the dynamics of infection. Moreover, the basic reproduction number
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Barriers to uptake of PrEP across the continuum among transgender women A global scoping review.
Although preexposure prophylaxis (PrEP) has demonstrated high efficacy for HIV prevention, rates of PrEP uptake remain low among the transgender population, especially in transgender women (TGW). We conducted this scoping review to assess and characterize barriers to PrEP use along the PrEP care continuum among TGW. We conducted this scoping review by searching studies in Embase, PubMed, Scopus, and Web of Science. Eligibility criteria included reporting a PrEP related quantitative result among TGW peer-reviewed and published in English between 2010-2021. Globally, high willingness (80%) to use PrEP was found, yet uptake and adherence (35.4%) were low. TGW experiencing hardship, including poverty, incarceration, and substance use, were associated with higher odds of PrEP awareness but lower odds of PrEP use. Structural and social barriers such as stigma, medical mistrust, and perceived racism can be important barriers for PrEP continuation. High social cohesion and hormone replacement therapy were associated with greater odds of awareness. In addition, our study confirmed prior research showing that PrEP does not lower feminizing hormone levels in TGW. Significant demographic factors among TGW that are associated with PrEP engagement. It is imperative to focus on TGW as a population with independent needs, requiring specific PrEP care guidelines and tailored resource allocation, that fully considers individual-, provider-, and communitystructural-level barriers and facilitators. The present review also indicates that combining PrEP care with GAHT or broader gender-affirmation care may facilitate PrEP use.
36,793,139
Rapid qualitative analysis approach to stakeholder and client interviews to inform mobile-based HIV testing in the U.S. Deep South.
The severity of the HIV epidemic in the United States rural South highlights geographic, socioeconomic, and racial disparities that disproportionately affect poor Black Americans. Approximately 16% of Alabamians living with HIV remain undiagnosed and just 37% of rural Alabamians have ever been tested for HIV. We conducted in-depth interviews with 22 key stakeholders involved in HIV prevention, testing, treatment, or community health initiatives, and 10 adults living in rural communities across Alabama to explore HIV testing challenges and opportunities. We utilized a rapid qualitative analysis approach and engaged community partners for feedback and discussion. This analysis will inform the implementation of a mobile HIV testing service in rural Alabama. The following themes were identified (1) Cultural norms, racism, poverty, and rurality impair access to healthcare. (2) Lack of sex education, low knowledge of HIV and perception of risk reinforce stigmas. (3) Messaging about Undetectable Untransmissible (U U) is not well understood in communities. (4) Community involvement may promote communication and trust between communities and testing advocates. (5) Novel testing strategies are acceptable and may diminish barriers. Working with community gatekeepers may be a key strategy to understand and promote acceptability of interventions new to rural Alabama and ameliorate stigma within communities. The implementation of new HIV testing strategies requires building and maintaining relationships with advocates, especially faith-based leaders, who engage people across many demographics.
36,793,113
Efficacy and safety of lenalidomide in HIV-associated cryptococcal meningitis patients with persistent intracranial inflammation an open-label, single-arm, prospective interventional study.
Patients with human immunodeficiency virus-associated cryptococcal meningitis (HIV-CM) have persistent intracranial inflammation despite negative cerebrospinal fluid (CSF) fungal cultures after optimal treatment for CM, which could be devastating for the central nervous system. However, a definitive treatment strategy for persistent intracranial inflammation despite optimal antifungal therapies is undefined. We identified 14 HIV-CM patients with persistent intracranial inflammation and conducted a 24-week, prospective, interventional study. All participants received lenalidomide (25 mg, p.o.) on days 1 to 21 of a 28-day cycle. Follow-up lasted for 24 weeks with visits at baseline and weeks 4, 8, 12, and 24. The primary endpoint was the change in clinical manifestations, routine CSF parameters, and MRI findings after lenalidomide treatment. An exploratory analysis was made on changes in cytokine levels in CSF. Safety and efficacy analyses were undertaken in patients who received at least one dose of lenalidomide. Of 14 participants, 11 patients completed the 24 weeks of follow-up. Rapid clinical remission following lenalidomide therapy was observed. Clinical manifestations (fever, headache, altered mentation) were reversed fully by week-4 and remained stable during follow-up. A significant reduction in white blood cell (WBC) count in CSF was noted occurred at week-4 (P 0.009). The median protein concentration in CSF decreased from 1.4 (0.7-3.2) gL at baseline to 0.9 (0.6-1.4) at week-4 (P 0.004). The median albumin concentration in CSF decreased from 79.2 (48.4-149.8) mgL at baseline to 55.3 (38.3-89.0) mgL at week-4 (P 0.011). The WBC count, protein level, and albumin level in CSF remained stable and approached a normal range through week-24. There was no significant change in immunoglobulin-G, intracranial pressure (ICP), or chloride-ion concentration at each visit. Brain MRI demonstrated multiple lesions to be absorbed post-therapy. Levels of tumor necrosis factor-α granulocyte colony stimulating factor, interleukin (IL)-6, and IL-17A decreased significantly during 24-week follow-up. Two (14.3%) patients had mild skin rash, which resolved spontaneously. Lenalidomide-related serious adverse events were not observed. Lenalidomide could improve persistent intracranial inflammation in HIV-CM patients significantly and was well tolerated without serious adverse events observed. And the additional randomized controlled study is required to further validate the finding.
36,793,080
Experiences with telemedicine for HIV care in two federally qualified health centers in Los Angeles a qualitative study.
The SARS-CoV-2 pandemic has resulted in an increase in telemedicine utilization for routine HIV care. However, there is limited information on perceptions of and experiences with telemedicine from United States (U.S.) federally qualified health centers (FQHCs) offering HIV care. We sought to understand telemedicine experiences of stakeholders with various roles people living with HIV (PLHIV), clinical (clinicians and case managers), programmatic (clinic administrators), and policy (policymakers). Qualitative interviews about benefits and challenges of telemedicine (telephone and video) for HIV care were conducted with 31 PLHIV and 23 other stakeholders (clinicians, case managers, clinic administrators, and policymakers). Interviews were transcribed, translated to English if conducted in Spanish, coded, and analyzed for major themes. Almost all PLHIV felt capable of engaging in telephone visits, with some expressing interest in learning how to use video visits as well. Nearly all PLHIV wanted to continue telemedicine as part of their routine HIV care, and this was also endorsed by clinical, programmatic and policy stakeholders. Interviewees agreed that telemedicine for HIV care has benefits for PLHIV, especially savings of time and transportation costs, which also reduced stress. Clinical, programmatic, and policy stakeholders expressed concerns around patients technological literacy and resources, as well as their access to privacy, and some felt that PLHIV strongly preferred in-person visits. These stakeholders also commonly reported clinic-level implementation challenges, including integrating telephone and video telemedicine into workflows and difficulty with video visit platforms. Telemedicine for HIV care, largely delivered via telephone (audio-only), was highly acceptable and feasible for both PLHIV, clinicians, and other stakeholders. Addressing barriers for stakeholders in incorporating video visits will be important for the successful implementation of telemedicine with video as part of routine HIV care at FQHCs.
36,793,070
Factors associated with health-related quality of life in people living with HIV in Norway.
Despite the advances in the treatment of HIV, people living with HIV (PLHIV) still experience impairment of health-related quality of life (HRQOL). The aim of the study was to explore factors associated with HRQOL in a well-treated Norwegian HIV population. Two hundred and forty-five patients were recruited from two outpatient clinics to participate in this cross-sectional study of addiction, mental distress, post-traumatic stress disorder, fatigue, somatic health, and HRQOL. The latter was measured using the 36-Item Short Form Health Survey (SF-36). Stepwise multiple linear regression analysis was used to examine the adjusted associations between demographic and disease-related variables and HRQOL. The study population was virologically and immunologically stable. Their mean age was 43.8 (SD 11.7) years, 131 (54%) were men, and 33% were native Norwegians. Compared with the general population (published in previous studies), patients reported worse SF-36 scores for five of eight domains mental health, general health, social function, physical role limitation, and emotional role limitation (all p < 0.001). Compared with men, women reported better SF-36 scores within the domains vitality (63.1 (23.6) vs. 55.9 (26.7), p 0.026) and general health (73.4 (23.2) vs. 64.4 (30.1), p 0.009). In the multivariate analyses, higher SF-36- physical component score values were independently associated with young age (p 0.020), being employed, student, or pensioner (p 0.009), low comorbidity score (p 0.015), low anxiety and depression score (p 0.015), being at risk of drug abuse (p 0.037), and not being fatigued (p < 0.001). Higher SF-36-mental component score values were independently associated with older age (p 0.018), being from a country outside Europe or from Norway (p 0.029), shorter time since diagnosis, low anxiety and depression score (p < 0.001), answering no regarding alcohol abuse (p 0.013), and not being fatigued (p < 0.001). HRQOL was poorer in PLHIV than in the general population in Norway. It is important to focus on somatic and mental comorbidities when delivering health-care services in the ageing population of PLHIV to improve HRQOL even among a well-treated group of PLHIV as found in Norway.
36,793,041
Factors associated with receptive injection equipment sharing among people who inject drugs findings from a multistate study at the start of the COVID-19 pandemic.
Receptive injection equipment sharing (i.e., injecting with syringes, cookers, rinse water previously used by another person) plays a central role in the transmission of infectious diseases (e.g., HIV, viral hepatitis) among people who inject drugs. Better understanding these behaviors in the context of COVID-19 may afford insights about potential intervention opportunities in future health crises. This study examines factors associated with receptive injection equipment sharing among people who inject drugs in the context of COVID-19. From August 2020 to January 2021, people who inject drugs were recruited from 22 substance use disorder treatment programs and harm reduction service providers in nine states and the District of Columbia to complete a survey that ascertained how the COVID-19 pandemic affected substance use behaviors. We used logistic regression to identify factors associated with people who inject drugs having recently engaged in receptive injection equipment sharing. One in four people who inject drugs in our sample reported having engaged in receptive injection equipment sharing in the past month. Factors associated with greater odds of receptive injection equipment sharing included having a high school education or equivalent (adjusted odds ratio aOR 2.14, 95% confidence interval 95% CI 1.24, 3.69), experiencing hunger at least weekly (aOR 1.89, 95% CI 1.01, 3.56), and number of drugs injected (aOR 1.15, 95% CI 1.02, 1.30). Older age (aOR 0.97, 95% CI 0.94, 1.00) and living in a non-metropolitan area (aOR 0.43, 95% CI 0.18, 1.02) were marginally associated with decreased odds of receptive injection equipment sharing. Receptive injection equipment sharing was relatively common among our sample during the early months of the COVID-19 pandemic. Our findings contribute to existing literature that examines receptive injection equipment sharing by demonstrating that this behavior was associated with factors identified in similar research that occurred before COVID. Eliminating high-risk injection practices among people who inject drugs requires investments in low-threshold and evidence-based services that ensure persons have access to sterile injection equipment.
36,793,018
The social determinants of national tuberculosis incidence rates in 116 countries a longitudinal ecological study between 2005-2015.
Accelerating declines in tuberculosis (TB) incidence is paramount for achieving global goals set for 2030 by the Sustainable Development Goals and the End TB Strategy. The aim of this study was to identify key country-level social determinants of national TB incidence trends. This longitudinal ecological study used country-level data extracted from online databases from the period 2005-2015. We used multivariable Poisson regression models allowing for distinct within- and between-country effects to estimate associations between national TB incidence rates and 13 social determinants of health. The analysis was stratified by country income status. The study sample included 48 low- and lower-middle-income countries (LLMICs) and 68 high- and upper-middle income countries (HUMICs), with a total of 528 and 748 observations between 2005-2015, respectively. National TB incidence rates declined in 108116 countries between 2005-2015, with an average drop of 12.95% in LLMICs and 14.09% in HUMICs. Between LLMICs, higher Human Development Index (HDI), social protection spending, TB case detection, and TB treatment success were associated with lower TB incidence. Higher prevalence of HIVAIDS was associated with higher TB incidence. Within LLMICs, increases in HDI over time were associated with lower TB incidence rates. Between HUMICs, higher HDI, health spending, and diabetes prevalence were associated with lower TB incidence, whereas higher prevalence of HIVAIDS and alcohol-use were associated with higher TB incidence. Within HUMICs, increases in HIVAIDS and diabetes prevalence over time were associated with higher TB incidence. In LLMICs, TB incidence rates remain highest in countries with low human development, social protection spending and TB programme performance, and high rates of HIVAIDS. Strengthening human development is likely to accelerate declines in TB incidence. In HUMICs, TB incidence rates remain highest in countries with low human development, health spending and diabetes prevalence, and high rates of HIVAIDS and alcohol use. Here, slowing rising rates of HIVAIDS and diabetes is likely to accelerate declines in TB incidence.
36,792,952
Association between metformin use and cognitive and physical function in persons with HIV and diabetes.
Older persons with HIV (PWH) experience high rates of cognitive impairment and frailty, and accelerated decline in physical function compared to the general population. Metformin use has been associated with beneficial effects on cognitive and physical function among older adults without HIV. The relationship between metformin use on these outcomes in PWH has not been evaluated. AIDS Clinical Trials Group (ACTG) A5322 is an observational cohort study of older PWH with annual assessments for cognition and frailty, including measures of physical function (e.g., gait speed and grip strength). Participants with diabetes who were prescribed anti-hyperglycemic medications were included in this analysis to evaluate the association between metformin and functional outcomes. Cross-sectional, longitudinal, and time-to-event models were used to evaluate the relationship between metformin exposure with cognitive, physical function, and frailty outcomes. Ninety-eight PWH met inclusion criteria and were included in at least one model. No significant associations between metformin use, frailty, physical or cognitive function were noted in unadjusted or adjusted cross-sectional, longitudinal, or time-to-event models (p>0.1 for all models). This study is the first to examine the association between metformin use on functional outcomes among older PWH. While it did not ascertain significant associations between metformin use and functional outcomes, our small sample size, restriction to persons with diabetes, and lack of randomization to metformin therapy were limitations. Larger, randomized studies are needed to determine whether metformin use has beneficial effects on cognitive or physical function in PWH.
36,792,792
Cross-municipality migration and spread of tuberculosis in South Africa.
Human migration facilitates the spread of infectious disease. However, little is known about the contribution of migration to the spread of tuberculosis in South Africa. We analyzed longitudinal data on all tuberculosis test results recorded by South Africas National Health Laboratory Service (NHLS), January 2011-July 2017, alongside municipality-level migration flows estimated from the 2016 South African Community Survey. We first assessed migration patterns in people with laboratory-diagnosed tuberculosis and analyzed demographic predictors. We then quantified the impact of cross-municipality migration on tuberculosis incidence in municipality-level regression models. The NHLS database included 921,888 patients with multiple clinic visits with TB tests. Of these, 147,513 (16%) had tests in different municipalities. The median (IQR) distance travelled was 304 (163 to 536) km. Migration was most common at ages 20-39 years and rates were similar for men and women. In municipality-level regression models, each 1% increase in migration-adjusted tuberculosis prevalence was associated with a 0.47% (95% CI 0.03% to 0.90%) increase in the incidence of drug-susceptible tuberculosis two years later, even after controlling for baseline prevalence. Similar results were found for rifampicin-resistant tuberculosis. Accounting for migration improved our ability to predict future incidence of tuberculosis.
36,792,544
Immune response to ART initiation in advanced HIV infection.
Our objective was to compare the immunological responses to commonly used antiretroviral therapy (ART) regimens among people with advanced HIV in the USA and to assess virological outcomes and regimen persistence. This study included ART-naïve adults with advanced HIV infection (CD4 cell count <200 cellsμL) initiating ART with bictegraviremtricitabinetenofovir alafenamide (BFTAF), boosted darunavir (bDRV), dolutegravir (DTG), or elvitegravir (EVGc)-containing regimens between 1 January 2018 and 31 December 2020 in the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) cohort. Cox proportional hazards models and linear mixed models with random intercept were fit with inverse probability of treatment weighting. Overall, 1349 people with advanced HIV (816 BFTAF, 253 DTG, 146 EVGc, 134 bDRV) were followed for a median of 22 months. Compared with BFTAF, a lower likelihood of achieving a CD4 cell count ≥200 cellsμL was observed with bDRV (hazard ratio HR 0.76 95% confidence interval CI 0.60-0.96), DTG (HR 0.82 95% CI 0.69-0.98), and EVGc (HR 0.73 95% CI 0.57-0.93). All groups had a similar pattern of CD4CD8 ratio changes a rapid increase in the first 6 months (ranging from 0.15 to 0.16 units), followed by a slower increase thereafter. Only 40 individuals (4%) achieved CD4CD8 ratio normalization (≥1). BFTAF was associated with a faster time to virological suppression (viral load <200 copiesmL) and a slower time to discontinuation compared with other regimens. Among people with advanced HIV infection, BFTAF initiation was associated with faster CD4 cell count recovery and favourable virological outcomes compared with bDRV-, DTG-, and EVGc-based regimens, although no difference was observed in CD4CD8 ratio changes over time across regimens.
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Scaling-up high-impact micronutrient supplementation interventions to improve adolescents nutrition and health in Burkina Faso and Tanzania protocol for a cluster-randomised controlled trial.
Adolescence is a critical time for growth and development, but this age group is often neglected in research and development of nutrition interventions. Despite recommendations from the WHO to provide nutrient supplements to adolescents, evidence remains scarce on the most effective supplementation strategy. This study aims to compare weekly iron and folic acid (IFA) supplementation with daily multiple micronutrient supplements (MMSs) in prevention of anaemia and improvement of school outcomes among adolescents in Burkina Faso and Tanzania. A three-arm cluster-randomised, school-based supplementation trial will be conducted among 84 schools (42 schools per site) and roughly 4500 students aged 10-17. Schools will be matched on three characteristics number of students, school ranking profile, distance to main road (Tanzania) or distance to city council (Burkina Faso). Each school will be randomised to receive either weekly IFA, daily MMSs or serve as a control. Supplements will be delivered to students by teachers, who will provide monitoring data to the study team. Baseline and endline surveys will be conducted prior to and after each supplementation cycle (12 weeks in Burkina Faso 1 year in Tanzania) to assess haemoglobin, anthropometry and sociodemographic variables. The primary outcome of haemoglobin will be analysed continuously using linear regression, and anaemia status will be analysed using logistic or multinomial regression, depending on categorisation level of the outcome. Secondary analyses of school performance indicators will also be conducted with either logistic or linear regression. This protocol has been approved by the Institutional Review Board of the Harvard TH Chan School of Public Health (IRB20-1108) and the Research Ethics Committees for the Ministries of Health in Tanzania (Zanzibar) and Burkina Faso. Results will be disseminated during meetings with the Ministries of Health and the participating communities as well as through peer-reviewed publications. NCT04657640 NCT05104554.