Long-term impact of immediate versus deferred antiretroviral therapy on kidney health in people with HIV.

People with human immunodeficiency virus (HIV) are at risk for chronic kidney disease (CKD) due to HIV and antiretroviral therapy (ART) nephrotoxicity. Immediate ART initiation reduces mortality and is now the standard of care, but the long-term impact of prolonged ART exposure on CKD is unknown. To evaluate this, the Strategic Timing of Antiretroviral Treatment (START) trial randomized 4,684 ART-naïve adults with CD4 cell count under 500 cells/mm3 to immediate versus deferred ART. We previously reported a small but statistically significantly greater decline in estimated glomerular filtration rate (eGFR) over a median of 2.1 years in participants randomized to deferred versus immediate ART. Here, we compare the incidence of CKD events and changes in eGFR and urine albumin/creatinine ratio (UACR) in participants randomized to immediate versus deferred ART during extended follow-up. Over a median of 9.3 years, eight participants experienced kidney failure or kidney-related death, three in the immediate and five in the deferred ART arms, respectively. Over a median of five years of more comprehensive follow-up, the annual rate of eGFR decline was 1.19 mL/min/1.73m2/year, with no significant difference between treatment arms (difference deferred - immediate arm 0.055; 95% confidence interval -0.106, 0.217 mL/min/1.73m2). Results were similar in models adjusted for baseline covariates associated with CKD, including UACR and APOL1 genotype. Similarly, there was no significant difference between treatment arms in incidence of confirmed UACR 30 mg/g or more (odds ratio 1.13; 95% confidence interval 0.85, 1.51). Thus, our findings provide the most definitive evidence to date in support of the long-term safety of early ART with respect to kidney health.

Experiences of patients living with HIV and AIDS on antiretroviral therapy in Accra, Ghana.

BACKGROUND:  The human immunodeficiency virus and acquired immunodeficiency syndrome (HIV and AIDS) pandemic has greatly affected Africa, particularly Ghana. The pandemic remains a public health concern, particularly in terms of accessing essential medication and improving quality of life for people living with the disease. OBJECTIVES:  This study aimed to explore and describe the experiences of persons diagnosed and living with HIV who are on antiretroviral therapy. METHOD:  A qualitative, exploratory, descriptive, and contextual design was used. The research population included persons diagnosed with HIV who were receiving antiretroviral therapy at three public hospitals in Ghana. Data saturation was achieved after conducting 15 semi-structured interviews. Creswell's six steps of data analysis were used to analyse the data, which resulted in the emergence of one main theme and six sub-themes. RESULTS:  The main theme identified by the researchers highlighted the participants' diverse experiences of being diagnosed and living with HIV. It was found that the study participants expressed shock, disbelief, surprise, and fear of death after being diagnosed with HIV. The participants also experienced stigmatisation, discrimination, and rejection. CONCLUSION:  There is a need for further research on the extent of discrimination and stigmatisation and the effect on optimal adherence to antiretroviral therapy. Continuous public education on HIV is required to limit the extent of discrimination and stigmatisation.Contribution: The study has highlighted the various emotions related to stigma and discrimination expressed by persons living with HIV (PLHIV). The findings will guide policy on eliminating discrimination and stigmatisation for people living with HIV.

Estimation of cause-specific mortality in Rakai, Uganda, using verbal autopsy 1999-2019.

BACKGROUND: There are scant data on the causes of adult deaths in sub-Saharan Africa. We estimated the level and trends in adult mortality, overall and by different causes, in rural Rakai, Uganda, by age, sex, and HIV status. OBJECTIVES: To estimate and analyse adult cause-specific mortality trends in Rakai, Uganda. METHODOLOGY: Mortality information by cause, age, sex, and HIV status was recorded in the Rakai Community Cohort study using verbal autopsy interviews, HIV serosurveys, and residency data. We estimated the average number of years lived in adulthood. Using demographic decomposition methods, we estimated the contribution of each cause of death to adult mortality based on the average number of years lived in adulthood. RESULTS: Between 1999 and 2019, 63082 adults (15-60 years) were censused, with 1670 deaths registered. Of these, 1656 (99.2%) had completed cause of death data from verbal autopsy. The crude adult death rate was 5.60 (95% confidence interval (CI): 5.33-5.87) per 1000 person-years of observation (pyo). The crude death rate decreased from 11.41 (95% CI: 10.61-12.28) to 3.27 (95% CI: 2.89-3.68) per 1000 pyo between 1999-2004 and 2015-2019. The average number of years lived in adulthood increased in people living with HIV and decreased in HIV-negative individuals between 2000 and 2019. Communicable diseases, primarily HIV and Malaria, had the biggest decreases, which improved the average number of years lived by approximately extra 12 years of life in females and 6 years in males. There were increases in deaths due to non-communicable diseases and external causes, which reduced the average number of years lived in adulthood by 2.0 years and 1.5 years in females and males, respectively. CONCLUSION: There has been a significant decline in overall mortality from 1999 to 2019, with the greatest decline seen in people living with HIV since the availability of antiretroviral therapy in 2004. By 2020, the predominant causes of death among females were non-communicable diseases, with external causes of death dominating in males.

Main findings: There are significant declines in mortality in people living with HIV. However, mortality in HIV-negative people increased due to non-communicable diseases in females, and injuries and external causes of death among males.Added knowledge: In this HIV-endemic area, decreasing adult mortality has been documented over the last 20 years. This paper benchmarks the changes in cause-specific mortality in this area.Global health impact for policy action: As in many African countries, more effort is needed to reduce mortality for non-communicable diseases, injuries, and external causes of death as these seem to have been neglected.

Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial.

BACKGROUND: HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB. METHODS: This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events. DISCUSSION: Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986.

Quality assessment of oral antimalarial and antiretroviral medicines used by public health systems in Sahel countries.

Malaria and Human Immunodeficiency Virus infections are among the top 10 causes of death in low income countries. Furthermore, many medicines used in these treatment areas are substandard, which contributes to the high death rate. Using a monitoring system to identify substandard and falsified medicines, the study aims to evaluate the quality of antimalarial and antiretroviral medicines in Sahel countries, assessing site conditions, compliance of medicines with pharmacopoeia tests, formulation equivalence with a reference medicine, and the influence of climate on quality attributes. Ultra Performance Liquid Chromatography methods for eight active pharmaceutical ingredients were validated following the International Conference for Harmonization guideline for its detection and quantification. Quality control consists of visual inspections to detect any misinformation or imperfections and pharmacopeial testing to determine the quality of pharmaceutical products. Medicines which complied with uniformity dosage units and dissolution tests were stored under accelerated conditions for 6 months. Artemether/Lumefantrine and Lopinavir/Ritonavir formulations failed uniformity dosage units and disintegration tests respectively, detecting a total of 28.6% substandard medicines. After 6 months stored under accelerated conditions (40 °C // 75% relative humidity) simulating climatic conditions in Sahel countries, some medicines failed pharmacopeia tests. It demonstrated the influence of these two factors in their quality attributes. This study emphasizes the need of certified quality control laboratories as well as the need for regulatory systems to maintain standards in pharmaceutical manufacturing and distribution in these countries, especially when medicines are transported to rural areas where these climatic conditions are harsher.

Projected Life Expectancy for Adolescents With HIV in the US.

Importance: Life expectancy is a key measure of overall population health. Life expectancy estimates for youth with HIV in the US are needed in the current HIV care and treatment context to guide health policies and resource allocation. Objective: To compare life expectancy between 18-year-old youth with perinatally acquired HIV (PHIV), youth with nonperinatally acquired HIV (NPHIV), and youth without HIV. Design, Setting, and Participants: Using a US-focused adolescent-specific Monte Carlo state-transition HIV model, we simulated individuals from age 18 years until death. We estimated probabilities of HIV treatment and care engagement, HIV progression, clinical events, and mortality from observational cohorts and clinical trials for model input parameters. The simulated individuals were 18-year-old race and ethnicity-matched youth with PHIV, youth with NPHIV, and youth without HIV; 47%, 85%, and 50% were assigned male sex at birth, respectively. Individuals were categorized by US Centers for Disease Control and Prevention-defined HIV acquisition risk: men who have sex with men, people who ever injected drugs, heterosexually active individuals at increased risk for HIV infection, or average risk for HIV infection. Distributions were 3%, 2%, 12%, and 83% for youth with PHIV and youth without HIV, and 80%, 6%, 14%, and 0% for youth with NPHIV, respectively. Among the simulated youth in this analysis, individuals were 61% Black, 24% Hispanic, and 15% White, respectively. Exposures: HIV status by timing of acquisition. Main Outcomes: Life expectancy loss for youth with PHIV and youth with NPHIV: difference between mean projected life expectancy under current and ideal HIV care scenarios compared with youth without HIV. Uncertainty intervals reflect varying adolescent HIV-related mortality inputs (95% CIs). Results: Compared with youth without HIV (life expectancy: male, 76.3 years; female, 81.7 years), male youth with PHIV and youth with NPHIV had projected life expectancy losses of 10.4 years (95% CI, 5.5-18.1) and 15.0 years (95% CI, 9.3-26.8); female youth with PHIV and youth with NPHIV had projected life expectancy losses of 11.8 years (95% CI, 6.4-20.2) and 19.5 years (95% CI, 13.8-31.6), respectively. When receiving ideal HIV care, life expectancy losses were projected to improve for youth with PHIV (male: 0.5 years [95% CI, 0.3-1.8]: female: 0.6 years [95% CI, 0.4-2.1]) but were projected to persist for youth with NPHIV (male: 6.0 years [95% CI, 5.0-9.1]; female: 10.4 years [95% CI, 9.4-13.6]). Conclusions: This adolescent-focused microsimulation modeling analysis projected that youth with HIV would have shorter life expectancy than youth without HIV. Projected differences were larger for youth with NPHIV compared with youth with PHIV. Differences in mortality by sex at birth, sexual behavior, and injection drug use contributed to lower projected life expectancy among youth with NPHIV. Interventions focused on HIV care and social factors are needed to improve life expectancy for youth with HIV in the US.

Guideline No. 450: Care of Pregnant Women Living with HIV and Interventions to Reduce Perinatal Transmission.

OBJECTIVE: This guideline provides an update on the care of pregnant women living with HIV and the prevention of perinatal HIV transmission. This guideline is a revision of the previous guideline, No. 310 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission, and includes an updated review of the literature with contemporary recommendations. TARGET POPULATION: Pregnant women newly diagnosed with HIV during antenatal screening and women living with HIV who become pregnant. This guideline does not include specific guidance for girls/women of reproductive age living with HIV who are not pregnant. OUTCOMES: Prevention of perinatal HIV transmission is a key indicator of the success of a health care system and requires multidisciplinary care of pregnant women living with HIV. Intended outcomes include guidance on best practice in perinatal management for Canadian health care providers for pregnant women living with HIV; reduction of perinatal transmission of HIV toward a target of eradication of perinatal transmission; provision of optimal antenatal care for pregnant women to ensure the best maternal health outcomes and HIV suppression; and evidence-based support and recommendations for pregnant women living with HIV, maintaining awareness and consideration of the complex psychosocial impacts of living with HIV. BENEFITS, HARMS, AND COSTS: The perinatal transmission of HIV has significant morbidity and mortality implications for the child, with associated lifelong health care costs. Pregnancy presents an emotionally and physically vulnerable time for pregnant women as well as an opportunity to engage them in health promotion. This guidance does not include recommendations with additional costs to health care facilities compared with the previous guideline. Application of the recommendations is aimed at health benefits to both mother and child by optimizing maternal health and preventing perinatal HIV transmission. EVIDENCE: Published and unpublished literature was reviewed with a focus on publications post-2013. OVID-Medline, Embase, PubMed and the Cochrane Library databases were searched for relevant publications available in English or French for each section of this guideline. Results included systematic reviews, randomized controlled trials, and observational studies published from 2012 to 2022. Searches were updated on a regular basis and incorporated in the guideline until May 2023. Unpublished literature, protocols, and international guidelines were identified by accessing the websites of health-related agencies, clinical practice guideline collections, and national and international medical specialty societies. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional recommendations). INTENDED AUDIENCE: The intended users of this guideline include obstetric care providers and infectious disease clinicians who provide care for pregnant women living with HIV. SOCIAL MEDIA SUMMARY: Updated Canadian HIV in pregnancy guideline informed by global research and tailored to Canadian healthcare needs and goals for pregnant women living with HIV and their families.

Human immunodeficiency virus infection is associated with greater risk of pneumonia and readmission after cardiac surgery.

Objective: Human immunodeficiency virus infection (HIV+) is associated with a 2-fold increased risk of cardiovascular disease. Increasingly, patients who are HIV + are being evaluated to undergo cardiac surgery. Current risk-adjusted scoring systems, including the Society of Thoracic Surgeons Predicted Risk of Mortality score, fail to stratify HIV + risk. Unfortunately, there exists a paucity of cardiac surgery outcomes data in modern patients who are HIV+. Methods: We conducted a retrospective review of PearlDiver, an all-payer claims administrative database. In total, 14,714,743 patients were captured between 2010 and 2020. Of these, 59,695 (0.4%) of patients had a history of HIV+, and 1759 (2.95%) of these patients underwent cardiac surgery. Patients who were HIV+ were younger, more often male, and had greater comorbidity, history of hypertension, chronic obstructive pulmonary disease, chronic liver disease, chronic kidney disease, chronic lung disease, and heart failure. Results: Postoperatively, patients who were HIV + had significantly greater rates of pneumonia (relative risk, 1.70; P = .0003) and 30-day all-cause readmission (relative risk, 1.28, P < .0001). After linear regression analysis, these results remained significant. Data also show that a lesser proportion of patients with HIV + underwent coronary artery bypass grafting, aortic valve replacement, and any cardiac surgery compared with controls. Conclusions: Patients who are HIV + undergoing cardiac surgery are at greater risk of pneumonia and readmission. Moreover, we discovered lower rates of cardiac surgery in patients who are HIV+, which may reflect limited access to surgery when indicated. Today's risk-adjusted scoring systems in cardiac surgery need to better account for the modern patient who is HIV+.

Improving linkage to HIV care following a reactive HIV self-testing result among men in KwaZulu-Natal, South Africa.

BACKGROUND: Despite the many interventions that have been implemented in sub-Saharan Africa to improve the uptake of HIV testing and antiretroviral (ART) initiation services, the rates at which men are tested for HIV and initiated on ART have remained consistently lower compared to those for women. We aim to investigate barriers and facilitators for linkage to care following HIVST positive results among men aged between 18 and 49 years, and use these findings to design an intervention to improve linkage to care among men in a high-HIV prevalent district in KwaZulu-Natal province, South Africa. METHODS: This multi-method study will be conducted over 24 months in eight purposively selected HIV testing and treatment facilities from December 2023 to November 2025. For the quantitative component, a sample of 197 HIV positive men aged 18-49 years old who link to care after HIV self-test (HIVST) will be recruited into the study. HIVST kits will be distributed to a minimum of 3000 men attending community services through mobile clinics that are supported by the Health Systems Trust, at different service delivery points, including schools, taxi ranks and other hotspots. The qualitative component will consist of in-depth interviews (IDIs) with 15 HIVST users and IDIs with 15 key informants. To design and develop acceptable, feasible, effective, and sustainable models for improving linkage to care, three groups of HIVST users (2*positive (N = 12) and 1*negative (N = 12)) will be purposively select to participate in a design workshop. Chi square tests will be used to identify social and demographic factors associated with linkage, while logistic regression will be used to identify independent factors. Kaplan Meier curves and cox proportional hazard models will be used to identify factors associated with time to event. Content and thematic approaches will be used to analyze the qualitative data. DISCUSSION: There remains an urgent need for designing and implementing innovative intervention strategies that are convenient and tailored for addressing the needs of men for improving HIV testing and linkage to care at early stages in resource-limited settings, to improve individual health outcomes, reduce transmission from HIV and minimize HIV-related mortality rates. Our proposed study offers several important innovations aimed at improving linkage to care among men. Our study targets men, as they lag the HIV continuum but are also under-researched in public health studies.

Screening for Hypertension in adolescents living with HIV: Protocol for a cluster randomized trial to improve guideline adherence.

BACKGROUND: Although AIDS-related deaths have reduced with increased access to antiretroviral care, cardiovascular disease-related morbidities among persons living with HIV are rising. Contributing to this is the higher incidence of Hypertension among Persons Living with HIV. The duration of exposure to the virus and antiretroviral drugs plays a vital role in the pathogenesis, putting perinatally infected children and adolescents at higher risk than behaviorally-infected ones, supporting the calls for increased surveillance of Hypertension among them. Despite the availability of guidelines to support this surveillance, the blood pressure (BP) of adolescents living with HIV (ADLHIV) is not checked during clinical visits. This study aims to assess the effect of a theory-based intervention on healthcare workers' adherence to the guidelines for hypertension screening among adolescents. METHODS: A multi-facility cluster-randomized study will be conducted. The clusters will be 20 antiretroviral therapy sites in the Greater Accra Region of Ghana with the highest adolescent caseload. Data will be extracted from the folders of adolescents (10-17 years) who received care in these facilities six months before the study. The ART staff of intervention facilities will receive a multicomponent theory of planned behaviour-based intervention. This will include orientation on hypertension risk among ADLHIV, provision of job aids and pediatric sphygmomanometers. Six months after the intervention, the outcome measure will be the change from baseline in the proportion of ADLHIV whose BP was checked during clinical visits. The calculated sample size is 400 folders. IMPLICATIONS OF FINDINGS: This study will generate evidence on the effectiveness of a multicomponent theory-based intervention for improving the implementation of clinical practice guidelines. TRIAL REGISTRATION: PACTR202205641023383.

Mpox in people with HIV: A narrative review.

OBJECTIVE: The 2022 global mpox outbreak disproportionately impacted people living with HIV. This review explores recent evidence on mpox in this group, focusing on clinical presentation, complications, treatment modalities and vaccine strategies. RECENT FINDINGS: Recent studies have suggested that people with HIV diagnosed with mpox have a greater risk of proctitis and hospitalization compared with people without HIV. In addition, those with advanced immunosuppression face an elevated risk of severe mpox infection, which can lead to mortality. Comprehensive and prompt supportive care using antiretrovirals and mpox antivirals is crucial in this group. Although results from randomized clinical trials are still forthcoming, recent studies suggest that early initiation of tecovirimat can prevent disease progression in people with HIV. The non-replicative attenuated smallpox vaccine is well tolerated and effective in preventing monkeypox virus infections in people with HIV. Further studies are needed regarding long-term vaccine effectiveness for this population. CONCLUSION: Evaluating the risk of severe mpox in people living with HIV requires assessing the level of immune suppression and viral control. Universal access to vaccination is imperative to prevent the resurgence of future outbreaks.

Using group norms to promote acceptance of HIV testing during household tuberculosis contact investigation: A household-randomized trial.

Background: HIV status awareness and linkage to care are critical for ending the HIV epidemic and preventing tuberculosis (TB). Among household contacts of persons with TB, HIV greatly increases the risk of incident TB and death. However, almost half of household contacts in routine settings decline HIV test offers during routine contact investigation. We evaluated a brief social-behavioral norming intervention to increase acceptance of HIV testing during household TB contact investigation. Methods: We carried out a household-randomized, controlled trial to evaluate the effect of the norming strategy among household contacts of persons with pulmonary TB in Kampala, Uganda ( ClinicalTrials.gov # NCT05124665 ). Community health workers (CHW) visited homes of persons with TB to screen contacts for TB symptoms and offer free, optional, oral HIV testing. Households were randomized (1:1) to usual care or the norming strategy. Contacts were eligible if they were ≥ 15 years old, self-reported to be HIV-negative, and living in a multi-contact household. The primary outcome, the proportion of contacts accepting HIV testing, was analyzed using an intention-to-treat approach, using a mixed-effects model to account for clustering by household. We assessed HIV testing yield as a proportion of all contacts tested. Results: We randomized 328 contacts in 99 index households to the norming strategy, of whom 285 (87%) contacts were eligible. We randomized 224 contacts in 86 index households to the usual strategy, of whom 187 (84%) contacts were eligible. Acceptance of HIV testing was higher in the intervention arm (98% versus 92%, difference +6%, 95%CI +2% to +10%, p=0.004). Yield of HIV testing was 2.1% in the intervention arm and 0.6% in the control arm (p=0.22). Conclusion: A norming intervention significantly improved uptake of HIV testing among household contacts of persons with TB. Funding/Support: This work was supported by the Center for Interdisciplinary Research on AIDS (P30MH062294) and the Fogarty International Center of the National Institutes of Health (R21TW011270). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other sponsors.

Immune checkpoint inhibition as a therapeutic strategy for HIV eradication: current insights and future directions.

PURPOSE OF REVIEW: HIV-1 infection contributes substantially to global morbidity and mortality, with no immediate promise of an effective prophylactic vaccine. Combination antiretroviral therapy (ART) suppresses HIV replication, but latent viral reservoirs allow the virus to persist and reignite active replication if ART is discontinued. Moreover, inflammation and immune disfunction persist despite ART-mediated suppression of HIV. Immune checkpoint molecules facilitate immune dysregulation and viral persistence. However, their therapeutic modulation may offer an avenue to enhance viral immune control for patients living with HIV-1 (PLWH). RECENT FINDINGS: The success of immune checkpoint inhibitor (ICI) therapy in oncology suggests that targeting these same immune pathways might be an effective therapeutic approach for treating PLWH. Several ICIs have been evaluated for their ability to reinvigorate exhausted T cells, and possibly reverse HIV latency, in both preclinical and clinical HIV-1 studies. SUMMARY: Although there are very encouraging findings showing enhanced CD8+ T-cell function with ICI therapy in HIV infection, it remains uncertain whether ICIs alone could demonstrably impact the HIV reservoir. Moreover, safety concerns and significant clinical adverse events present a hurdle to the development of ICI approaches. This review provides an update on the current knowledge regarding the development of ICIs for the remission of HIV-1 in PWH. We detail recent findings from simian immunodeficiency virus (SIV)-infected rhesus macaque models, clinical trials in PLWH, and the role of soluble immune checkpoint molecules in HIV pathogenesis.

Clinical Outcomes After Acute Coronary Syndromes or Revascularization Among People Living With HIV: A Systematic Review and Meta-Analysis.

Importance: Clinical outcomes after acute coronary syndromes (ACS) or percutaneous coronary interventions (PCIs) in people living with HIV have not been characterized in sufficient detail, and extant data have not been synthesized adequately. Objective: To better characterize clinical outcomes and postdischarge treatment of patients living with HIV after ACS or PCIs compared with patients in an HIV-negative control group. Data Sources: Ovid MEDLINE, Embase, and Web of Science were searched for all available longitudinal studies of patients living with HIV after ACS or PCIs from inception until August 2023. Study Selection: Included studies met the following criteria: patients living with HIV and HIV-negative comparator group included, patients presenting with ACS or undergoing PCI included, and longitudinal follow-up data collected after the initial event. Data Extraction and Synthesis: Data extraction was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Clinical outcome data were pooled using a random-effects model meta-analysis. Main Outcome and Measures: The following clinical outcomes were studied: all-cause mortality, major adverse cardiovascular events, cardiovascular death, recurrent ACS, stroke, new heart failure, total lesion revascularization, and total vessel revascularization. The maximally adjusted relative risk (RR) of clinical outcomes on follow-up comparing patients living with HIV with patients in control groups was taken as the main outcome measure. Results: A total of 15 studies including 9499 patients living with HIV (pooled proportion [range], 76.4% [64.3%-100%] male; pooled mean [range] age, 56.2 [47.0-63.0] years) and 1 531 117 patients without HIV in a control group (pooled proportion [range], 61.7% [59.7%-100%] male; pooled mean [range] age, 67.7 [42.0-69.4] years) were included; both populations were predominantly male, but patients living with HIV were younger by approximately 11 years. Patients living with HIV were also significantly more likely to be current smokers (pooled proportion [range], 59.1% [24.0%-75.0%] smokers vs 42.8% [26.0%-64.1%] smokers) and engage in illicit drug use (pooled proportion [range], 31.2% [2.0%-33.7%] drug use vs 6.8% [0%-11.5%] drug use) and had higher triglyceride (pooled mean [range], 233 [167-268] vs 171 [148-220] mg/dL) and lower high-density lipoprotein-cholesterol (pooled mean [range], 40 [26-43] vs 46 [29-46] mg/dL) levels. Populations with and without HIV were followed up for a pooled mean (range) of 16.2 (3.0-60.8) months and 11.9 (3.0-60.8) months, respectively. On postdischarge follow-up, patients living with HIV had lower prevalence of statin (pooled proportion [range], 53.3% [45.8%-96.1%] vs 59.9% [58.4%-99.0%]) and ß-blocker (pooled proportion [range], 54.0% [51.3%-90.0%] vs 60.6% [59.6%-93.6%]) prescriptions compared with those in the control group, but these differences were not statistically significant. There was a significantly increased risk among patients living with HIV vs those without HIV for all-cause mortality (RR, 1.64; 95% CI, 1.32-2.04), major adverse cardiovascular events (RR, 1.11; 95% CI, 1.01-1.22), recurrent ACS (RR, 1.83; 95% CI, 1.12-2.97), and admissions for new heart failure (RR, 3.39; 95% CI, 1.73-6.62). Conclusions and Relevance: These findings suggest the need for attention toward secondary prevention strategies to address poor outcomes of cardiovascular disease among patients living with HIV.

Statistical analysis on the incidence and predictors of death among second-line ART patients in public hospitals of North Wollo and Waghemira Zones, Ethiopia, 2021.

Acquired immune deficiency virus, caused by the human immunodeficiency virus, is a significant global health concern. Sub-Saharan Africa particularly Ethiopia faces a high prevalence of human immunodeficiency virus. In low-income settings like Ethiopia, early mortality rates are elevated due to severe opportunistic infections and advanced disease at Anti-retroviral treatment initiation. Despite available treatments, delayed treatment initiation among Human Immunodeficiency Virus -infected individuals in Africa, including Ethiopia, leads to disease progression and increased mortality risk. This study aimed to identify the factors contributing to the death of HIV patients under treatment at second line regimen in public hospitals of North Wollo and Waghemira Zones. A retrospective cohort study with 474 patients was conducted in selected hospitals of North Wollo and Waghemira Zones. A parametric Weibull regression model was employed, and the adjusted hazard ratio served as the measure of association. Variables significantly affected the outcome of the study was determined at a p-value < 0.05, along with a 95% confidence interval for the variables. The patients were within the average age of 38.6(standard deviation ± 12.5) years and majority (45.57%) had no formal education. The overall death incidence rate among second-line anti-retroviral treatment patients was 1.98 per 100-person years [95% CI 1.4-2.9%]. Poor adherence to antiretroviral treatment, male gender, and being underweight significantly increased the hazard of death. Conversely, increased anti-retroviral treatment duration had a significant and negative impact, reducing the hazard of death among patients. The study reveals a high incidence of death among second line anti-retroviral treatment users. Independent predictors include poor adherence, male gender, and underweight status, all significantly increasing the risk of death. On the positive side, the hazard of death decreases with longer anti-retroviral treatment duration. A critical concern and counseling should be given for better ART adherence, to change their nutritional status and for males.

Mortality among extrapulmonary tuberculosis patients in the HIV endemic setting: lessons from a tertiary level hospital in Mbeya, Tanzania.

Extrapulmonary tuberculosis (EPTB) has received less attention than pulmonary tuberculosis due to its non-contagious nature. EPTB can affect any organ and is more prevalent in people living with HIV. Low- and middle-income countries are now facing the double burden of non-communicable diseases (NCDs) and HIV, complicating the management of patients with symptoms that could be compatible with both EPTB and NCDs. Little is known about the risk of death of patients presenting with symptoms compatible with EPTB. We included patients with a clinical suspicion of EPTB from a tertiary level hospital in Mbeya, Tanzania, to assess their risk of dying. A total of 113 (61%) patients were classified as having EPTB, and 72 (39%) as having non-TB, with corresponding mortality rates of 40% and 41%. Associated factors for mortality in the TB groups was hospitalization and male sex. Risk factors for hospitalization was having disease manifestation at any site other than lymph nodes, and comorbidities. Our results imply that NCDs serve as significant comorbidities amplifying the mortality risk in EPTB. To strive towards universal health coverage, focus should be on building robust health systems that can tackle both infectious diseases, such as EPTB, and NCDs.

Prevalence trends of anemia impairment in adolescents and young adults with HIV/AIDS.

BACKGROUND: Anemia is a common complication of HIV/AIDS, particularly in adolescents and young adults across various countries and regions. However, little is known about the changing prevalence trends of anemia impairment in this population over time. METHODS: Data on anemia in adolescents and young adults with HIV/AIDS from 1990 to 2019 were collected from the Global Burden of Disease. Prevalence was calculated by gender, region, and country for individuals aged 10-24, and trends were measured using estimating annual percentage changes (EAPC). RESULTS: Globally, the prevalence of adolescents and young adults with HIV/AIDS increased from 103.95 per 100,000 population in 1990 to 203.78 in 2019. However, anemia impairment has decreased over the past three decades, with a global percentage decreasing from 70.6% in 1990 to 34.7% in 2019, mainly presenting as mild to moderate anemia and significantly higher in females than males. The largest decreases were observed in Central Sub-Saharan Africa, North America, and Eastern Sub-Saharan Africa, with EAPCs of -2.8, -2.34, and -2.17, respectively. Tajikistan (78.76%) and Madagascar (74.65%) had the highest anemia impairment percentage in 2019, while China (16.61%) and Iceland (13.73%) had the lowest. Anemia impairment was closely related to sociodemographic index (SDI) levels, with a high proportion of impairment in low SDI regions but a stable decreasing trend (EAPC = -0.37). CONCLUSION: Continued anemia monitoring and management are crucial for patients with HIV, especially in high-prevalence regions and among females. Public health policies and interventions can improve the quality of life and reduce morbidity and mortality.

Development and Pilot-Testing of an Optimized Conversational Agent or "Chatbot" for Peruvian Adolescents Living With HIV to Facilitate Mental Health Screening, Education, Self-Help, and Linkage to Care: Protocol for a Mixed Methods, Community-Engaged Study.

BACKGROUND: Adolescents living with HIV are disproportionally affected by depression, which worsens antiretroviral therapy adherence, increases viral load, and doubles the risk of mortality. Because most adolescents living with HIV live in low- and middle-income countries, few receive depression treatment due to a lack of mental health services and specialists in low-resource settings. Chatbot technology, used increasingly in health service delivery, is a promising approach for delivering low-intensity depression care to adolescents living with HIV in resource-constrained settings. OBJECTIVE: The goal of this study is to develop and pilot-test for the feasibility and acceptability of a prototype, optimized conversational agent (chatbot) to provide mental health education, self-help skills, and care linkage for adolescents living with HIV. METHODS: Chatbot development comprises 3 phases conducted over 2 years. In the first phase (year 1), formative research will be conducted to understand the views, opinions, and preferences of up to 48 youths aged 10-19 years (6 focus groups of up to 8 adolescents living with HIV per group), their caregivers (5 in-depth interviews), and HIV program personnel (5 in-depth interviews) regarding depression among adolescents living with HIV. We will also investigate the perceived acceptability of a mental health chatbot, including barriers and facilitators to accessing and using a chatbot for depression care by adolescents living with HIV. In the second phase (year 1), we will iteratively program a chatbot using the SmartBot360 software with successive versions (0.1, 0.2, and 0.3), meeting regularly with a Youth Advisory Board comprised of adolescents living with HIV who will guide and inform the chatbot development and content to arrive at a prototype version (version 1.0) for pilot-testing. In the third phase (year 2), we will pilot-test the prototype chatbot among 50 adolescents living with HIV naïve to its development. Participants will interact with the chatbot for up to 2 weeks, and data will be collected on the acceptability of the chatbot-delivered depression education and self-help strategies, depression knowledge changes, and intention to seek care linkage. RESULTS: The study was awarded in April 2022, received institutional review board approval in November 2022, received funding in December 2022, and commenced recruitment in March 2023. By the completion of study phases 1 and 2, we expect our chatbot to incorporate key needs and preferences gathered from focus groups and interviews to develop the chatbot. By the completion of study phase 3, we will have assessed the feasibility and acceptability of the prototype chatbot. Study phase 3 began in April 2024. Final results are expected by January 2025 and published thereafter. CONCLUSIONS: The study will produce a prototype mental health chatbot developed with and for adolescents living with HIV that will be ready for efficacy testing in a subsequent, larger study. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55559.

Piloting Siyakhana: A community health worker training to reduce substance use and depression stigma in South African HIV and TB care.

South Africa has one of the highest rates of HIV/tuberculosis (TB) co-infection, and poor engagement in HIV/TB care contributes to morbidity and mortality. In South Africa, community health workers (CHWs) are tasked with re-engaging patients who have dropped out of HIV/TB care. CHWs have described substantial challenges with substance use (SU) and depression among their patients, while patients have described CHW stigma towards SU and depression as barriers to re-engagement in care. Yet, CHWs receive little-to-no training on SU or depression. Therefore, we piloted Siyakhana, a brief CHW training to reduce stigma related to SU and depression while improving skills for re-engaging these patients in HIV and/or TB care. This study evaluated the preliminary effectiveness (stigma towards SU and depression; clinical competence assessed via roleplay) and implementation (quantitative ratings of feasibility, acceptability, appropriateness, adoption; semi-structured written qualitative feedback) of Siyakhana among CHWs and supervisors (N = 17) at pre- and post-training assessments. SU stigma significantly decreased (F(1,16) = 18.94, p < 0.001, ηp2 = 0.54). Depression stigma was lower than SU stigma at both timepoints and did not significantly decrease after training. CHW clinical competency towards patients with SU/depression significantly improved (t(11) = -3.35, p = 0.007, d = 1.00). The training was rated as feasible, acceptable, appropriate, and likely to be adopted by CHWs and their supervisors. Nonjudgmental communication was commonly described as the most useful training component. Based on this pilot, the training is being refined and evaluated in a larger randomized stepped-wedge clinical trial.

Impact of HIV status on prognosis of malignancies among people living with HIV in Japan.

BACKGROUND: Antiretroviral therapy has reduced the incidence and mortality of AIDS-defining malignancies (ADM); however, non-AIDS-defining malignancies (NADM) are a major cause of death among people living with HIV (PLWH) today. Though current guidelines suggest that PLWH should receive the same treatment as the general population, there are limited studies focused on how HIV status affects the prognosis of cancers. The present study aimed to investigate the characteristics and prognosis of malignant diseases among PLWH in Japan. METHODS: Patients with HIV diagnosed with malignant diseases at our institution between 2011 and 2021 were retrospectively reviewed. RESULTS: There were 205 patients who were diagnosed with malignancies. Of these, 87 (42.4%) were diagnosed with ADM and 118 (57.6%) were diagnosed with NADM. Among 69 patients who received chemotherapy for ADM, 24 (34.8%) developed AIDS-defining opportunistic infections during treatment. In contrast, only one (1.8%) of the 56 patients administered chemotherapy for NADM developed AIDS-defining opportunistic infections. Complications of opportunistic infections at diagnosis of malignancies, low CD4+ T-cell count, positive HIV RNA, and nonadministration of antiretroviral therapy were associated with 5-year overall survival among patients with malignant lymphomas. However, the variables associated with HIV did not affect NADM prognosis. CONCLUSIONS: In this analysis, HIV status had a small impact on the prognosis of malignant diseases in PLWH. Few patients with NADM developed AIDS-defining opportunistic infections after receiving chemotherapy.