The Mulher Study: cervical cancer screening with primary HPV testing in Mozambique

Objective To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally. Methods Women aged 30­49 years were prospectively enrolled and offered primary HPV testing using either self- collected or provider- collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected. Results Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 30­49) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self- collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV- positive patients, 2588 (92.3%) returned for all steps of their diagnostic work- up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty- one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology. Conclusion It is feasible to perform cervical cancer screening with primary HPV testing and follow- up in low- resource settings. Participants preferred self- collection, and the majority of screen- positive patients completed all steps of their diagnostic work- up and treatment. Our findings provide important information for further implementation and scale- up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.

Markers of Maternal Bone and Renal Toxicity Through 50 Weeks Postpartum: IMPAACT 2010 (VESTED) Trial.

BACKGROUND: Safety data from randomized trials of antiretrovirals in pregnancy are scarce. We evaluated maternal bone and renal data from the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 trial, which compared the safety and efficacy of 3 antiretroviral therapy regimens started in pregnancy: dolutegravir + emtricitabine/tenofovir alafenamide (DTG + FTC/TAF), dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG + FTC/TDF), and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). METHODS: A subset of participants underwent dual-energy X-ray absorptiometry scans at postpartum week 50 only. Maternal bone mineral density (BMD) Z-scores were compared between arms. Maternal creatinine was measured at enrolment and periodically through week 50 postpartum, and by-arm differences in average weekly change in estimated creatinine clearance were compared. RESULTS: Six hundred forty-three participants were randomized to DTG + FTC/TAF (N = 217) or DTG + FTC/TDF (N = 215) or EFV/FTC/TDF (N = 211). Median age = 27 years (IQR 23, 32), median CD4 count = 466 cells/mm3 (IQR 308, 624); 564 (88%) women enrolled in Africa and 479 (74%) breastfed. Week 50 postpartum dual-energy X-ray absorptiometry results from 154 women were included in the analysis. Hip and spine BMD was on average higher in women in the DTG + FTC/TAF and lower in the DTG + FTC/TDF and EFV/FTC/TDF arms, but no significant differences in BMD Z-scores were observed between treatment groups. The weekly rate of change in estimated creatinine clearance differed among treatment groups during the antepartum period, but not over the full study follow-up. CONCLUSIONS: Markers of bone and renal toxicity did not differ significantly through week 50 postpartum among women randomized to start DTG + FTC/TAF or DTG + FTC/TDF or EFV/FTC/TDF in pregnancy.

Efficacy of Internet Recruitment and HIV Self-Testing for Diagnosing HIV Infections Among Black and Hispanic/Latino MSM and Transgender Women in 11 US States, 2020-2021.

INTRODUCTION: We evaluated internet platforms for distributing HIV self-tests (HIVSTs) to Black or African American (Black) and Hispanic or Latino men who have sex with men (MSM) and transgender women (TGW). METHODS: We recruited MSM and TGW from general interest, dating, and lesbian, gay, bisexual, and transgender platforms. Two HIVSTs were mailed to all MSM and TGW. Surveys (screening, baseline, 4-month, and results reporting) were completed online. After 4 months, participants were mailed another HIVST and a dried blood spot card. All HIVST interpretations and images of HIVST devices were reported online. RESULTS: Of 2093 MSM and 102 TGW, most were recruited through general interest and dating platforms. Over 50% were 18-29 years old, most identified as gay or bisexual. Overall, 45% had not tested for HIV in the past 12 months, and 9.1% of MSM reported a positive (reactive for HIV antibodies) HIVST result, with the highest percentage among Black MSM (11.5%). Dating platforms recruited higher percentages of MSM who recorded positive results compared with MSM from general interest platforms during the intervention period (11.9% vs 5.5% (P < 0.0001)), and MSM who had never tested for HIV reported a greater percentage of positive HIVST results compared with MSM who had been tested for HIV before enrollment (16.1% vs. 7.1%; P < 0.0001). MSM were able to correctly interpret and report HIVST results. Of TGW, 7% reported a positive HIVST result. CONCLUSIONS: Internet dating and general interest platforms can be key to increasing awareness of infection among BMSM, HMSM, and TGW persons, including those who do not use existing HIV services. TRIAL REGISTRATION: www.clinicaltrials.gov Identifier: NCT04219878.

Adherence of healthcare providers to Enhanced Adherence Counseling (EAC) intervention protocol in West Amhara Public Health Facilities, Northwest Ethiopia, 2023: mixed method evaluation.

BACKGROUND: In Ethiopia, there were an estimated 670,906 people living with the Human Immune Virus (HIV). Implementing an HIV test and treat strategy and rapid scale-up of anti-retroviral treatment (ART) provided health facilities increased the number of the number of people living with HIV/AIDS. In the same way, the expansion of viral load monitoring in these health facilities and poor adherence to ART increase the number of high-viral load (HVL) patients. To alleviate this problem, the World Health Organization (WHO) recommended EAC intervention for HVL patients. Therefore, the aim of this research was to determine the level of healthcare providers' adherence to the EAC intervention protocol and explore barriers and facilitators of the intervention in West Amhara, Northwest Ethiopia. METHOD: Descriptive cross-sectional study design with concurrent mixed-method evaluation was employed. The adherence dimension, with its sub-dimensions of content, coverage, frequency, and duration of the EAC intervention, was used with sixteen indicators. A total of 20 high-case-load public health facilities and 173 HVL patients were included in our study. Quantitative data was entered into Epi Info and exported to SPSS version 25 for analysis. Descriptive statistics are analyzed in terms of frequencies, percentages, variances, and means and presented as narrations, frequency tables, graphs, and charts. Qualitative data were transcribed, translated, coded, and analyzed thematically using Open Code version 4.0 software. The qualitative findings were used to triangulate the quantitative findings. RESULT: The average adherence level of health care providers (HCPs) to the EAC intervention protocol was 55.3%, from which content, coverage, frequency, and duration of the intervention contributed 70.3%, 86.3%, 36.9%, and 27.7%, respectively. Most of the intervention contents were delivered during the session, but none of the providers developed a patient adherence plan at the end of the session. All HVL patients were linked and enrolled in the EAC intervention. But only 6% of them were tested for repeat VL. CONCLUSION: The average adherence level of HCPs to the EAC intervention protocol was very inadequate. The main gap identified was difficulties in completing the EAC intervention sessions based on schedules. Implementing adherence improvement strategies, assigning an adequate number of EAC providers in ART and Prevention of Mother-to-Child Transmission (PMTCT) clinics, and allowing sufficient time during EAC sessions are important.

Knowledge, attitudes and beliefs regarding HIV among medical students in Zagreb, Croatia.

BACKGROUND: Medical students, as future health-care providers (HCPs) play a significant role in shaping attitudes towards people living with HIV/AIDS (PLWHA) and should possess adequate knowledge of this infection. The study aim was to assess knowledge about HIV among medical students of the University of Zagreb School of Medicine, and to determine the level of discriminatory attitudes towards PLWHA. METHODS: We assessed knowledge about epidemiology, treatment, and prevention of HIV by using closed-ended and multiple-choice questions. Likert-scale questions were employed to determine attitudes towards PLWHA. Bivariate and multivariate ordinal logistic regression was used to assess correlates of certain discriminatory attitudes. RESULTS: 561 medical students participated, with 46.7% attending preclinical courses. Overall, 42.1% of students think they received sufficient information on HIV/AIDS during elementary and high school education. Among clinical students, 42.6%, 20.8% and 11.8% estimated accurately transmission risk after a needle injury, unprotected vaginal, and anal intercourse, respectively. 66.8% of clinical students were aware that treatment can prevent AIDS, while 58.7% and 69.8% were familiar with the rationale of using pre-exposure (PrEP) and post-exposure prophylaxis (PEP). In the multivariate analysis, individuals lacking infectology course attendance (aOR = 1.45; CI: 1.00-2.09) and those unaware of transmission routes (aOR = 1.49; CI: 1.06-2.09) showed higher odds of advocating HIV status disclosure compared to those who did not yet attend an infectology course. Students supporting extra protection for handling PLWHA bodily fluids were more likely to support refusal to treat PLWHA (aOR = 1.80; CI: 1.22-2.69) compared to those who did not support that opinion. Males were more inclined to state that they would refuse to treat PLWHA (aOR = 1.66; CI: 1.11-2.50) and disclose their HIV status (aOR = 1.62; CI: 1.17-2.27) than females. Overestimating needle injury transmission risk raised treatment refusal likelihood (aOR = 2.22; CI = 1.29-3.92) compared to those accurately informed of this risk. CONCLUSION: Results indicate lack of knowledge of HIV transmission risks after specific exposures and about PrEP, PEP and treatment effectiveness. Gender and knowledge about HIV transmission risks influence students' attitudes towards PLWHA. Medical education should be focused on fostering correct attitudes and addressing stigma, which undermines prevention and treatment outcomes of PLWHA.

Expanding single-venue services to better engage young people who inject drugs: insights from India.

BACKGROUND: Over the last decade, India has had an alarming rise in injection of opioids across several cities. Although scale-up of public sector services for people who inject drugs (PWID) in India has occurred over decades, accessibility has been diminished by fragmented services across physical locations. To circumvent this barrier, and in alignment with the World Health Organization's guidelines to provide comprehensive care to key populations, Integrated Care Centers (ICCs) were established across 8 Indian cities as a public-private service delivery model for providing free single-venue services to PWID. ICCs have been very successful in expanding service availability and convenience for PWID generally. However, few studies from low- and middle-income countries (LMIC) have evaluated how well young PWID (defined as those ≤ 29 years of age) engage with single-venue service models like ICCs or specific services provided in such models. Young PWID are an important subpopulation in India, as they bear a disproportionate burden of new HIV infections because of greater risk and evidence of lower receipt of HIV testing and harm reduction services compared to older PWID. In this comment, we offer insights specific to young PWID drawn from multiple quantitative and qualitative studies examining the reach and effectiveness of ICCs, which may provide generalizable insights into limitations of services for young PWID more broadly in India and globally. FINDINGS: Our studies suggest that while ICCs have expanded service availability, particularly in cities with emerging injection drug use epidemics, population-level reach to foster initial engagement among young PWID can be optimized. Additionally, young PWID who do engage with ICCs experience gaps in substance use treatment receipt and retention, and experience barriers to receipt of ICC services that are distinct from those experienced by older PWID. Notably, HIV incidence among ICC clients is concentrated in young PWID. Finally, ICCs were not intended to reach adolescent PWID, and new services are needed for this subpopulation. CONCLUSIONS: In addition to co-locating services, iterative optimization of models such as ICCs should incorporate youth-specific differentiated interventions and be accompanied by policy changes that are critical to improving the reach and effectiveness of harm reduction and HIV services among young PWID in India.

HIV drug resistance: analysis of viral genotypes and mutation loci in people living with HIV in Chongqing, China (2016-2023).

BACKGROUND: Large-scale HIV genotype drug resistance study has not been conducted in Chongqing. METHODS: A retrospective study was conducted on people living with HIV(PLWH) who received HIV-1 genotype resistance testing at Chongqing Public Health Medical Center from May 2016 to June 2023. The HIV-1pol gene was amplified through RT-PCR and analyzed in terms of genotypic drug resistance. RESULTS: Of the 3015 PLWH tested for HIV-1 drug resistance, 1405 (46.6%) were resistant to at least one antiviral drug. Among non-nucleoside reverse transcriptase inhibitors (NNRTIs), 43.8% were resistant, compared to 29.5% for nucleoside reverse transcriptase inhibitors (NRTIs) and 3.4% for protease inhibitors (PIs). V179D/E and K103N/S were identified as the common mutation sites in the NNRTIs class of drugs, M184V/I and K65R/N were reported as the most common mutation sites in NRTIs, while thymidine analogue mutation (TAM) group was identified in 373 samples. L10FIV was the most common mutation in PIs. The dominant HIV-1 subtype was CRF07_BC. CONCLUSIONS: The high prevalence of HIV-1 drug resistance in Chongqing underscores the imperative for rigorous surveillance of the local HIV epidemic. Furthermore, TAMs are associated with HIV-1 multidrug resistance, and timely detection of drug resistance is helpful to reduce the emergence and spread of such drug-resistant strains.

Myocardial infarction with non-obstructive coronary arteries in a young seropositive woman with human immunodeficiency virus: a case report and review of the literature.

BACKGROUND: Elevated susceptibility to acute myocardial infarction and various cardiovascular diseases has been observed in individuals infected with the human immunodeficiency virus compared with the uninfected population, as demonstrated in numerous studies. The precise mechanism by which human immunodeficiency virus infection heightens the risk of acute myocardial infarction remains elusive. The manifestation of acute coronary syndrome in young patients with human immunodeficiency virus may deviate from the typical, displaying distinct pathophysiological and clinical characteristics. The occurrence of myocardial infarction with non-obstructive coronary arteries in young patients with human immunodeficiency virus poses diagnostic and treatment challenges. CASE PRESENTATION: We present the case of a 46-year-old African woman with no traditional atherosclerotic risk factors. She was diagnosed with human immunodeficiency virus-1 infection 2 years prior to her current admission for chest pain. Her troponin levels were elevated, suggestive of acute coronary syndrome. Although coronary angiography ruled out coronary artery stenosis, it revealed mild myocardial bridging in the left anterior descending artery. Cardiac magnetic resonance imaging confirmed myocardial infarction, indicating a myocardial infarction with non-obstructive coronary arteries with an apical thrombus in the left ventricle. Following medical treatment, the patient experienced resolution of chest pain and improvement in ST-segment elevation. CONCLUSIONS: In young female patients without traditional risk factors, human immunodeficiency virus infection is a possible etiological factor for myocardial infarction with non-obstructive coronary arteries. The likely pathophysiological pathway is superficial endothelial cell denudation as a result of chronic inflammation and immune activation.

Structural and Functional Dysregulation of the Brain Endothelium in HIV Infection and Substance Abuse.

Blood-brain barrier (BBB) injury and dysfunction following infection with the human immunodeficiency virus (HIV) enables viral entry into the brain, infection of resident brain cells, neuronal injury and subsequent neurodegeneration leading to HIV-associated neurocognitive disorders (HAND). Although combination antiretroviral therapy has significantly reduced the incidence and prevalence of acquired immunodeficiency syndrome and increased the life expectancy of people living with HIV, the prevalence of HAND remains high. With aging of people living with HIV associated with increased comorbidities, the prevalence of HIV-related central nervous system (CNS) complications is expected to remain high. Considering the principal role of the brain endothelium in HIV infection of the CNS and HAND, the purpose of this manuscript is to review the current literature on the pathobiology of the brain endothelium structural and functional dysregulation in HIV infection, including in the presence of HIV-1 and viral proteins (gp120, Tat, Nef, and Vpr). We summarize evidence from human and animal studies, in vitro studies, and associated mechanisms. We further summarize evidence of synergy or lack thereof between commonly abused substances (cocaine, methamphetamine, alcohol, tobacco, opioids, and cannabinoids) and HIV- or viral protein-induced BBB injury and dysfunction.

The HIV-1 capsid serves as a nanoscale reaction vessel for reverse transcription.

The viral capsid performs critical functions during HIV-1 infection and is a validated target for antiviral therapy. Previous studies have established that the proper structure and stability of the capsid are required for efficient HIV-1 reverse transcription in target cells. Moreover, it has recently been demonstrated that permeabilized virions and purified HIV-1 cores undergo efficient reverse transcription in vitro when the capsid is stabilized by addition of the host cell metabolite inositol hexakisphosphate (IP6). However, the molecular mechanism by which the capsid promotes reverse transcription is undefined. Here we show that wild type HIV-1 virions can undergo efficient reverse transcription in vitro in the absence of a membrane-permeabilizing agent. This activity, originally termed "natural endogenous reverse transcription" (NERT), depends on expression of the viral envelope glycoprotein during virus assembly and its incorporation into virions. Truncation of the gp41 cytoplasmic tail markedly reduced NERT activity, suggesting that gp41 licenses the entry of nucleotides into virions. By contrast to reverse transcription in permeabilized virions, NERT required neither the addition of IP6 nor a mature capsid, indicating that an intact viral membrane can substitute for the function of the viral capsid during reverse transcription in vitro. Collectively, these results demonstrate that the viral capsid functions as a nanoscale container for reverse transcription during HIV-1 infection.

Progress Toward Achieving National HIV/AIDS Strategy Goals for Quality of Life Among Persons Aged ≥50 Years with Diagnosed HIV - Medical Monitoring Project, United States, 2017-2023.

Ensuring good quality of life (QoL) among persons with diagnosed HIV (PWH) is a priority of the National HIV/AIDS Strategy (NHAS), which established 2025 goals for improving QoL. Goals are monitored through five indicators: self-rated health, unmet needs for mental health services, unemployment, hunger or food insecurity, and unstable housing or homelessness. Among the growing population of PWH aged ≥50 years, progress toward these goals has not been assessed. Data collected during the 2017-2022 cycles of the Medical Monitoring Project, an annual complex sample survey of U.S. adults with diagnosed HIV, assessed progress toward NHAS 2025 QoL goals among PWH aged ≥50 years, overall and by age group. The recent estimated annual percentage change from baseline (2017 or 2018) to 2022 was calculated for each indicator. Among PWH aged ≥50 years, the 2025 goal of 95% PWH with good or better self-rated health is 46.2% higher than the 2022 estimate. The 2025 goals of a 50% reduction in the other indicators range from 26.3% to 56.3% lower than the 2022 estimates. Decreasing hunger or food insecurity by 50% among PWH aged ≥65 was the only goal met by 2022. If recent trends continue, other NHAS QoL 2025 goals are unlikely to be met. Multisectoral strategies to improve access to housing, employment, food, and mental health will be needed to meet NHAS 2025 goals for QoL among older PWH.

Advanced HIV disease and its predictors among newly diagnosed PLHIV in the Gedeo zone, southern Ethiopia.

BACKGROUND: Globally, HIV infection remains a leading cause of morbidity and mortality. Despite reducing new infections, the global response to advanced HIV disease (AHD) remains ineffective, leaving HIV epidemics a significant public health threat worldwide. In Ethiopia, evidence regarding AHD is scarce. Therefore, this study aimed to assess the prevalence and predictors of AHD among newly diagnosed people living with HIV (PLHIV) initiating antiretroviral therapy in the Gedeo zone, southern Ethiopia. METHODS: A facility-based cross-sectional study was conducted from May 29, 2023, to February 06, 2024, at health facilities providing HIV care in the Gedeo zone, southern Ethiopia. A total of 427 PLHIV-initiating antiretroviral therapy (ART) were recruited for the study. The data were collected through face-to-face interviews and record reviews using KoboCollect version 2.4 and analyzed using R version 4.3.3. The Akaike information criterion (AIC) model selection was used to evaluate and choose the best-fitting model to describe the relationship between AHD and predictors. Finally, variables with a p-value less than 0.05 were considered independent predictors in the multivariable regression analysis. RESULTS: The study participants' mean (±SD) age was 31.3 (±8.7) years. The overall prevalence of AHD among newly diagnosed PLHIV-initiating ART was 34.4% (95% CI: 29.8%, 39.1%). Rural residence (AOR = 3.48, 95% CI: 2.24, 5.47), alcohol consumption (AOR = 2.48, 95% CI: 1.59, 3.90), and being identified through community-based index case testing (ICT) (AOR = 0.26, 95% CI: 0.13, 0.51) were found to be independent predictors of AHD. CONCLUSIONS: The prevalence of AHD among newly diagnosed individuals initiating ART was high. PLHIV who consume alcohol should receive detailed counseling on how it can negatively impact their progress with antiretroviral treatment. HIV testing should be enhanced in rural communities by strengthening community health campaigns. Furthermore, community-based index case testing should be strengthened for early identification of PLHIV.

The Enigmatic Interplay of Interleukin-10 in the Synergy of HIV Infection Comorbid with Preeclampsia.

Cytokines coordinate the intricate choreography of the immune system, directing cellular activities that mediate inflammation, pathogen defense, pathology and tissue repair. Within this spectrum, the anti-inflammatory prowess of interleukin-10 (IL-10) predominates in immune homeostasis. In normal pregnancy, the dynamic shift of IL-10 across trimesters maintains maternal immune tolerance ensuring fetal development and pregnancy success. Unravelling the dysregulation of IL-10 in pregnancy complications is vital, particularly in the heightened inflammatory condition of preeclampsia. Of note, a reduction in IL-10 levels contributes to endothelial dysfunction. In human immunodeficiency virus (HIV) infection, a complex interplay of IL-10 occurs, displaying a paradoxical paradigm of being immune-protective yet aiding viral persistence. Genetic variations in the IL-10 gene further modulate susceptibility to HIV infection and preeclampsia, albeit with nuanced effects across populations. This review outlines the conceptual framework underlying the role of IL-10 in the duality of normal pregnancy and preeclampsia together with HIV infection, thus highlighting its regulatory mechanisms and genetic influences. Synthesizing these findings in immune modulation presents avenues for therapeutic interventions in pregnancy complications comorbid with HIV infection.

Bacterial Infections in Patients Living with HIV.

Pneumonia, as well as other types of acute and chronic lung injuries, remain the leading causes of death in individuals living with HIV. Individuals with HIV who are on antiretroviral therapy continue to have a greater risk for pneumonia, including bacterial and mycobacterial infections. Alveolar macrophages and lung epithelial cells constitute the first line of host defense against invading pathogens. The predisposition of individuals living with HIV to infections despite ante-retroviral therapy is mechanistically related to HIV pro-viruses integrating into host cells, including airway epithelial cells and alveolar macrophages. Alveolar macrophages harbor latent HIV even when individuals appear to have complete suppression on ART. In parallel, pneumonia can irreversibly impair lung function in HIV-infected individuals. Cells that Macrophages exposed to HIV or HIV-related proteins have been shown to secrete exosomes that contain miRNAs. These exosomes can regulate several innate and acquired immune functions by stimulating cytokine production and inflammatory responses. Furthermore, these secreted exosomal miRNAs can shuttle between cells, causing cellular dysfunction in the case of epithelial cells; they disrupt lung epithelial barrier dysfunction, which leads to a predisposition to bacterial infections. We discuss the common bacterial infections that occur in patients living with HIV and provide mechanistic insights into how the intercellular communication of miRNAs results in cellular dysfunction.

State of HIV costing in Latin America and the Caribbean: a systematic literature review / Estado actual de la información sobre los costos de la infección por el VIH en América Latina y el Caribe: Revisión bibliográfica sistemática / Cálculo do custo do HIV na América Latina e no Caribe: revisão sistemática da literatura

[ABSTRACT]. Objectives. To summarize available data on unit costs for human immunodeficiency virus (HIV) testing, prevention, and care interventions in Latin America and the Caribbean. Methods. We conducted a systematic literature review of costing studies published between 2012 and 2024, and selected those reporting empirically measured costing data. The available data were categorized according to predefined intervention categories and compared by time and place. We also explored variations in unit costs by intervention type. Results. Of 1 746 studies identified, 22 met the inclusion criteria, which provided 103 unique unit cost estimates from nine countries. About 50% of the included studies were published between 2019 and 2021. Antiretroviral therapy services had the most cost data available (39% of unit costs), followed by inpatient care (27%) and HIV testing (24%). Considerable cost variations were observed both within and between interventions. Conclusions. Our analysis underscores the need for accurate and reliable cost data to support HIV budgeting and decision-making efforts. We identified several gaps in the availability of cost data and emphasize the importance of presenting results more effectively by incorporating key contextual variables. Given the challenges of shrinking budgets and sustainability risks, robust evidence is indispensable to inform priority setting and budget allocation for HIV services.

[RESUMEN]. Objetivos. Resumir los datos disponibles sobre los costos unitarios de las intervenciones en materia de pruebas de detección, prevención y atención de salud relacionadas con el virus de la inmunodeficiencia humana (VIH) en América Latina y el Caribe. Métodos. Se realizó una revisión bibliográfica sistemática de los estudios sobre costos publicados entre el 2012 y el 2024, y se seleccionaron los estudios que presentaban datos de costos determinados de manera empírica. Los datos disponibles se clasificaron en categorías de intervención predefinidas y se compararon en función del tiempo y el lugar. También se examinaron las variaciones en los costos unitarios según el tipo de intervención. Resultados. De los 1746 estudios encontrados, 22 cumplían los criterios de inclusión; y en ellos se obtuvieron 103 estimaciones distintas de costos unitarios procedentes de nueve países. Alrededor del 50% de los estudios incluidos se publicaron entre el 2019 y el 2021. Los servicios de tratamiento antirretroviral eran los que disponían de más datos sobre costos (39% de los costos unitarios), seguidos de los de atención hospitalaria (27%) y los de pruebas de detección del VIH (24%). Se observaron variaciones considerables en los costos en una misma intervención y entre distintas intervenciones. Conclusiones. En este análisis se subraya la necesidad de disponer de datos de costos exactos y fiables para brindar apoyo a los esfuerzos de elaboración de presupuestos y la toma de decisiones en materia de infección por el VIH. Detectamos varias brechas en cuanto a la disponibilidad de datos sobre costos y hacemos hincapié en la importancia de presentar los resultados de manera más eficaz mediante la incorporación de variables contextuales clave. Ante los desafíos que plantean la reducción presupuestaria y los riesgos para su sostenibilidad, es indispensable contar con evidencia sólida para fundamentar la determinación de prioridades y la asignación de presupuestos a los servicios relacionados con la infección por el VIH.

[RESUMO]. Objetivos. Sintetizar os dados disponíveis sobre os custos unitários de testagem, prevenção e intervenções de saúde relacionados ao vírus da imunodeficiência humana (HIV) na América Latina e Caribe. Métodos. Foi realizada uma revisão sistemática da literatura de estudos de custeio publicados entre 2012 e 2024, com a seleção de estudos que apresentavam dados de custeio medidos empiricamente. Os dados foram classificados em categorias predefinidas de intervenção e comparados por tempo e lugar. Variações nos custos unitários por tipo de intervenção também foram examinadas. Resultados. Dos 1746 estudos identificados, 22 preencheram os critérios de inclusão, fornecendo 103 estimativas de custos unitários em nove países. Cerca de 50% dos estudos incluídos na análise foram publicados entre 2019 e 2021. A maior parte dos dados de custo se referiam a serviços de terapia antirretroviral (39% dos custos unitários), serviços de atenção hospitalar (27%) e serviços de testagem de HIV (24%). Foram observadas variações de custo consideráveis para uma mesma intervenção e entre diferentes intervenções. Conclusões. Esta análise aponta a necessidade de se dispor de dados de custo exatos e confiáveis para apoiar o processo decisório e a alocação de recursos orçamentários relacionados ao HIV. Foram identificadas várias lacunas na disponibilidade de dados de custo. Enfatiza-se a importância de apresentar os resultados com mais eficiência, incorporando as principais variáveis contextuais. Diante dos desafios impostos pela retração orçamentária e pelos riscos à sustentabilidade, é imprescindível dispor de evidências robustas para subsidiar o processo de estabelecimento de prioridades e alocação de recursos orçamentários para serviços de HIV.

Cohort profile: Rahima Moosa Mother and Child Hospital maternal HIV cohort, Johannesburg, South Africa.

PURPOSE: The Rahima Moosa Mother and Child Hospital (RMMCH) maternal HIV cohort originated from data systems that were developed to support HIV-related birth care and track outcomes of a complete birth cohort of HIV-exposed infants at Rahima Moosa Hospital and their mothers living with HIV. PARTICIPANTS: Supported by the Empilweni Services and Research Unit, maternal and infant data from 13 654 pregnant women living with HIV who delivered their infants (and a subset also attended antenatal care) were collected at RMMCH in Johannesburg, South Africa since 2013. Maternal data were collected using counsellor-administered interviews and the 2013-2018 subset of this cohort was linked to the National Health Laboratory Services (NHLS) national HIV cohort-a longitudinal cohort of people living with HIV accessing care in the public sector antiretroviral therapy programme in South Africa that can observe national access to HIV care through laboratory testing data. FINDINGS TO DATE: Topics addressed by the cohort include antenatal care history, HIV treatment exposure, delivery/birth management, prophylaxis and maternal blood results relevant to HIV captured at delivery. The cohort was also one of the first to describe implementation of early infant diagnosis procedures in South Africa including evaluations of novel point-of-care testing strategies demonstrating improvements in uptake of HIV care among infants accessing point-of-care services. FUTURE PLANS: Annual linkage of infant delivery and testing data to longitudinal laboratory test data in the NHLS national HIV cohort is planned to allow for analysis of both infant continuity of care outcomes and as well as evaluation of maternal-infant pair treatment and mobility outcomes in the post partum and later period.

Immunization of cows with HIV envelope trimers generates broadly neutralizing antibodies to the V2-apex from the ultralong CDRH3 repertoire.

The generation of broadly neutralizing antibodies (bnAbs) to conserved epitopes on HIV Envelope (Env) is one of the cornerstones of HIV vaccine research. The animal models commonly used for HIV do not reliably produce a potent broadly neutralizing serum antibody response, with the exception of cows. Cows have previously produced a CD4 binding site response by homologous prime and boosting with a native-like Env trimer. In small animal models, other engineered immunogens were shown to focus antibody responses to the bnAb V2-apex region of Env. Here, we immunized two groups of cows (n = 4) with two regimens of V2-apex focusing Env immunogens to investigate whether antibody responses could be generated to the V2-apex on Env. Group 1 was immunized with chimpanzee simian immunodeficiency virus (SIV)-Env trimer that shares its V2-apex with HIV, followed by immunization with C108, a V2-apex focusing immunogen, and finally boosted with a cross-clade native-like trimer cocktail. Group 2 was immunized with HIV C108 Env trimer followed by the same HIV trimer cocktail as Group 1. Longitudinal serum analysis showed that one cow in each group developed serum neutralizing antibody responses to the V2-apex. Eight and 11 bnAbs were isolated from Group 1 and Group 2 cows, respectively, and showed moderate breadth and potency. Potent and broad responses in this study developed much later than previous cow immunizations that elicited CD4bs bnAbs responses and required several different immunogens. All isolated bnAbs were derived from the ultralong CDRH3 repertoire. The finding that cow antibodies can target more than one broadly neutralizing epitope on the HIV surface reveals the generality of elongated structures for the recognition of highly glycosylated proteins. The exclusive isolation of ultralong CDRH3 bnAbs, despite only comprising a small percent of the cow repertoire, suggests these antibodies outcompete the long and short CDRH3 antibodies during the bnAb response.

Spatial patterns and associated factors of HIV testing and counselling (HTC) as a component of antenatal care services in Ethiopia.

BACKGROUND: While HIV testing and counselling play a crucial role in preventing mother-to-child transmission, numerous pregnant women did not receive these services. Understanding the spatial variation of HIV testing and counselling and its associated factors during antenatal care in Ethiopia remains limited. Thus, this study was aimed at assessing the spatial patterns and factors associated with HIV testing and counselling during antenatal care visits in Ethiopia. METHODS: A cross-sectional study design was employed with a two-stage stratified cluster sampling technique. A total of 2,789 women who gave birth in the two years prior to the survey and had at least one antenatal care visit were included in the study. Stata version 16 and ArcGIS version 10.8 software were used for analysis. A multilevel robust Poisson regression model was fitted to identify significantly associated factors since the prevalence of HIV testing and counselling was higher than 10%. A statistically significant association was declared based on multivariable multilevel robust Poisson regression analysis using an adjusted prevalence ratio with its 95% confidence interval at a p-value < 0.05. Spatial regression analysis was conducted, and the local coefficients of statistically significant spatial covariates were visualised. RESULTS: In Ethiopia, the overall prevalence of HIV testing and counselling during antenatal care visits was 29.5% (95% CI: 27.8%, 31.2%). Significant spatial clustering was observed (Global Moran's I = 0.138, p-value <0.001). In the spatial regression analysis, high and comprehensive knowledge related to HIV, and comprehensive knowledge on the prevention of mother-to-child transmission were significant explanatory variables for the spatial variation of HIV testing and counselling. In the multivariable multilevel robust Poisson regression analysis, education, household wealth, media exposure, number of antenatal care visits, comprehensive knowledge on mother-to-child transmission, comprehensive knowledge on prevention of mother-to-child transmission, and region were significantly associated factors. CONCLUSION: The prevalence of HIV testing and counselling during antenatal care visits was low. Empowering women through education, promoting mass media exposure, increasing numbers of antenatal care visits, and enhancing women's knowledge related to HIV and mother-to-child transmission by targeting cold spot areas could improve HIV testing and counselling service uptake among pregnant women in Ethiopia.

An optimized strategy triggered at the 2nd immunization visit to prevent HIV acquisition by breastfeeding: a phase 2 trial in Burkina Faso (PREVENIR-PEV).

BACKGROUND: Mother-to-child transmission of HIV during breastfeeding remains a challenge in low- and middle-income countries (LMIC). A prevention package was initiated during the highly attended 2nd visit of the Expanded Program of Immunisation (EPI-2) to identify the undiagnosed infants living with HIV and reduce the postnatal transmission of infant exposed to HIV. METHODS: PREVENIR-PEV is a non-randomized phase II clinical trial conducted at two health centres in Bobo Dioulasso (Burkina Faso). The study recruited mothers living with HIV aged 15 years and older with their singleton breastfed infants. During EPI-2 (at 8 weeks) and upon signature of the informed consent, a point-of-care early infant diagnosis (EID) was performed. HIV exposed uninfected (HEU) infants were followed-up until 12 months of age. High risk HEU infants (i.e., whose maternal viral load ≥ 1000 cp/mL at EPI-2 or M6) received an extended postnatal prophylaxis (PNP) with lamivudine until end of follow-up or the end of breastfeeding. RESULTS: Between 4 December 2019 and 4 December 2020, 118 mothers living with HIV-1 were identified, and 102 eligible mother/infant pairs had their infants tested for HIV EID. Six infants were newly diagnosed with HIV, and 96 HEU infants were followed-up for 10 months. Among the participants followed-up, all mothers were prescribed antiretrovirals. All 18 infants eligible for PNP at either EPI-2 or 6 months (M6) were initiated on lamivudine. No HIV transmission occurred, and no serious adverse events were reported in infants receiving lamivudine. CONCLUSIONS: The PREVENIR-PEV prevention package integrated into existing care is safe and its implementation is feasible in a LMIC with a low HIV prevalence. More research is needed to target mother/infant pairs not adhering to the intervention proposed in this trial. TRIAL REGISTRATION: NCT03869944; first registered on 11/03/2019.

Europe must continue to lead on harm reduction.

Europe has been at the forefront of harm reduction since its inception. These important early steps were in large part a response to the dramatically expanding HIV epidemic, and investing in these innovative interventions early and robustly had a transformative effect. This brought about not just pioneering services but also pioneering policy changes. However, while Western Europe and Member States in the European Union often have been at the vanguard of harm reduction innovation and vocal advocates for public health and human rights-based drug policy reform, the situation has been much different in the "wider" WHO European region, which also includes Eastern and Southeastern Europe as well as Central Asia. This is a result not just of limited budgets for health, but also of punitive laws and policies and persistent stigma and discrimination. Even as harm reduction has demonstrated huge successes in Europe, there is a need to move forward a wider array of services to respond to an evolving and increasingly complex drug situation in Europe. Instead, it is a lack of political will and of political courage that is holding back the establishment, expansion, and deepening of these essential, lifesaving interventions. Responding proactively and effectively to this changing drug situation will require redoubled investment in public health and harm reduction approaches.