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.

Viral diseases and the environment relationship.

Viral diseases have been present throughout human history, with early examples including influenza (1500 B.C.), smallpox (1000 B.C.), and measles (200 B.C.). The term "virus" was first used in the late 1800s to describe microorganisms smaller than bacteria, and significant milestones include the discovery of the polio virus and the development of its vaccine in the mid-1900s, and the identification of HIV/AIDS in the latter part of the 20th century. The 21st century has seen the emergence of new viral diseases such as West Nile Virus, Zika, SARS, MERS, and COVID-19. Human activities, including crowding, travel, poor sanitation, and environmental changes like deforestation and climate change, significantly influence the spread of these diseases. Conversely, viral diseases can impact the environment by polluting water resources, contributing to deforestation, and reducing biodiversity. These environmental impacts are exacerbated by disruptions in global supply chains and increased demands for resources. This review highlights the intricate relationship between viral diseases and environmental factors, emphasizing how human activities and viral disease progression influence each other. The findings underscore the need for integrated approaches to address the environmental determinants of viral diseases and mitigate their impacts on both health and ecosystems.

Exploring Co-Amorphous Formulations Of Nevirapine: Insights From Computational, Thermal, And Solubility Analyses.

This study aimed to assess the formation of nevirapine (NVP) co-amorphs systems (CAM) with different co-formers (lamivudine-3TC, citric acid-CAc, and urea) through combined screening techniques as computational and thermal studies, solubility studies; in addition to develop and characterize suitable NVP-CAM. NVP-CAM were obtained using the quench-cooling method, and characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and polarized light microscopy (PLM), in addition to in vitro dissolution in pH 6.8. The screening results indicated intermolecular interactions occurring between NVP and 3TC; NVP and CAc, where shifts in the melting temperature of NVP were verified. The presence of CAc impacted the NVP equilibrium solubility, due to hydrogen bonds. DSC thermograms evidenced the reduction and shifting of the endothermic peaks of NVP in the presence of its co-formers, suggesting partial miscibility of the compounds. Amorphization was proven by XRD and PLM assays. In vitro dissolution study exhibited a significant increase in solubility and dissolution efficiency of NVP-CAM compared to free NVP. Combined use of screening studies was useful for the development of stable and amorphous NVP-CAM, with increased NVP solubility, making CAM promising systems for combined antiretroviral therapy.

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.

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.

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.

Co-occurring Intimate Partner Violence, Mental Health, Human Immunodeficiency Virus, and Parenting Among Women: A Scoping Review.

Little research exists on the human immunodeficiency virus (HIV)-intimate partner violence (IPV)-mental health (MH) syndemic impact on parenting. The objective of this scoping review is to identify and summarize the available evidence regarding the syndemic relationship between HIV or Acquired Immune Deficiency Syndrome (AIDS), IPV, and poor MH among mothers and caregivers who identify as women. We conducted the review according to the Joanna Briggs Institute and Preferred Reporting Items for Systematic reviews and meta-analyses extension for scoping reviews guidelines, a comprehensive search was conducted from 2001 to September 2023. The inclusion criteria targeted studies examining at least two of the HIV, IPV, or MH epidemics among participants and their syndemic impact on parenting. Both qualitative and quantitative studies were included. Covidence software was used to screen and extract data. Twenty-three studies were included in the analysis. Most of the studies were conducted in the United States. Furthermore, all the studies used quantitative research designs, with most being longitudinal. Most of the research was concentrated on the IPV-MH syndemic with no research found on the HIV-IPV syndemic impact on parenting. Research on the HIV-IPV-MH syndemic found that an HIV diagnosis exacerbated the negative impacts of IPV-MH on parenting. Research on IPV-MH showed that this syndemic significantly influences parenting, leading to less nurturing and more punitive behaviors. Studies did not find a direct association between IPV and harsh parenting practices, the relationship was mediated by poor MH. Studies examining the HIV-MH syndemic found that anxiety and maternal depression were the most frequent MH disorders. The review revealed that living with the different syndemics, (IPV-MH-HIV, HIV-MH, and IPV-MH) adversely affects parenting practices, resulting in harsher parenting.

Ten Recommendations for Accelerating Hypertension and Diabetes Control to Reduce Stroke, Heart, and Renal Disease with the Aim to Save Lives in Cameroon Through Partnerships and Collaborations.

Hypertension and diabetes are currently the most common, treatable, and controllable cardiovascular and metabolic risk factors for stroke, heart, and renal diseases in Cameroon. Hypertension affects 30% of adults aged ≥ 20 years with 90% as uncontrolled cases, while type 2 diabetes affects 6% of the same population, with 70% remaining underdiagnosed. Despite publication of the first Roadmap on raised blood pressure by the World Heart Federation in 2015, the Pan African Society of Cardiology Roadmap in 2017, and the technical package for cardiovascular disease management in primary health care (WHO-HEARTS) in 2020, very little progress has been made in improving the diagnosis, treatment, and control of cardiovascular risk factors and diseases in Cameroon. The Cameroon Cardiac Society and a dozen Cameroon non-communicable diseases societies, national organizations from the community and the civil society, along with researchers and members of academia and the health sector, came together under the patronage of representatives of the government to propose new strategies to improve hypertension and diabetes control and save lives in Cameroon. Two simple and practical algorithms for the management of hypertension and diabetes were developed. The ten recommendations tailored to be efficiently implemented in our country were summarized under the acronym 'A SMART VIEW' (Awareness, Screening, Manufacture, Activity, Research, Task-shifting, HIV/AIDS, Insurance, Education, and WHO-HEARTS). It is our hope that all stakeholders will further collaborate to remove barriers and enhance facilitators to deploy the proposed actions and reduce the burden of uncontrolled hypertension and untreated diabetes in Cameroon.

Hypertension and diabetes are very common, yet treatable, cardiovascular, and metabolic risk factors for stroke, heart, and renal diseases in Cameroon. One-third of all adults aged 20 years or more in Cameroon have hypertension, in most of whom it remains uncontrolled. In addition, while 6% of these adults have type 2 diabetes, more than two-thirds remain underdiagnosed. Despite efforts to improve the diagnosis, treatment, and control of cardiovascular risk factors and diseases in Cameroon, minimal progress has been made. The Cameroon Cardiac Society, supported by input from Cameroon non-communicable diseases societies, national institutions/organizations, and representatives from the community, research, academia, and the health sector, has now developed two practical algorithms and ten recommendations specific to the Cameroonian population in an attempt to improve the control of hypertension and diabetes in Cameroon. It is hoped that these stakeholders will further collaborate to ensure the efficient implementation of these recommendations across the country, with the ongoing aim of monitoring their effectiveness over the next five years.

Safe Sex and the Debate over Condoms on Campus in the 1980s: Sperm Busters at Harvard and Protection Connection at the University of Texas at Austin.

During the 1980s, college students in the United States helped to destigmatize the distribution and use of condoms. They shifted their aims from preventing unwanted pregnancy to stopping the spread of sexually transmitted infections including the newly identified acquired immunodeficiency syndrome (AIDS). Two student-led initiatives to deliver condoms after hours at Harvard University in Cambridge, Massachusetts and the University of Texas at Austin show regional and temporal differences in sexual mores as awareness of AIDS increased. These male students adopted a non-pharmaceutical intervention to prevent pregnancy and disease in the context of increased marketing of Trojan® brand condoms. Interviews with co-founders reveal how the students grappled with backlash from family members and campus administrators less enthusiastic about their popularization of condoms. Co-founders described how media attention affected their college experiences and how condom companies changed campus culture. Overall, large non-pharmaceutical companies such as Trojan® and small condom-resellers such as those at Harvard and the University of Texas at Austin reshaped cultural norms around safe sex as awareness of AIDS grew between 1985 and 1987.

Drug-drug interactions in hiv-infected patients receiving chemotherapy.

INTRODUCTION: Coadministration of antiretrovirals and anti-cancer medications may present many complex clinical scenarios. This is characterized by the potential for drug-drug interactions (DDIs) and the challenges that arise in patient management. In this paper, we investigate the potential for drug-drug interactions between antiretrovirals, including protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), Integrase strand transfer inhibitors (INSTIs), and anti-cancer medications. AREAS COVERED: PubMed, Google Scholar, and Clinicaltrials.gov were searched for relevant articles in April 2024. Our review highlights protease inhibitors and NNRTIs as particularly prone to DDIs with anticancer agents, with implications for efficacy and toxicity of concomitant cancer therapy. We explain the mechanisms for interactions, emphasizing the significance of pharmacokinetic effects and enzyme induction or inhibition. We discuss clinical challenges encountered in the management of patients receiving combined ART and cancer therapy regimens. EXPERT OPINION: Data is lacking for potential drug-drug interactions between antiretroviral and anti-cancer agents. While some interactions are documented, others are theoretical and based on the pharmacokinetic properties of the medications. Awareness of these interactions, inter-collaborative care between healthcare providers, and standardized treatment guidelines are all crucial for achieving optimal treatment outcomes and ensuring the well-being of patients with HIV/AIDS and cancer comorbidities.

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.

Antiviral capacity of the early CD8 T-cell response is predictive of natural control of SIV infection: Learning in vivo dynamics using ex vivo data.

While most individuals suffer progressive disease following HIV infection, a small fraction spontaneously controls the infection. Although CD8 T-cells have been implicated in this natural control, their mechanistic roles are yet to be established. Here, we combined mathematical modeling and analysis of previously published data from 16 SIV-infected macaques, of which 12 were natural controllers, to elucidate the role of CD8 T-cells in natural control. For each macaque, we considered, in addition to the canonical in vivo plasma viral load and SIV DNA data, longitudinal ex vivo measurements of the virus suppressive capacity of CD8 T-cells. Available mathematical models do not allow analysis of such combined in vivo-ex vivo datasets. We explicitly modeled the ex vivo assay, derived analytical approximations that link the ex vivo measurements with the in vivo effector function of CD8-T cells, and integrated them with an in vivo model of virus dynamics, thus developing a new learning framework that enabled the analysis. Our model fit the data well and estimated the recruitment rate and/or maximal killing rate of CD8 T-cells to be up to 2-fold higher in controllers than non-controllers (p = 0.013). Importantly, the cumulative suppressive capacity of CD8 T-cells over the first 4-6 weeks of infection was associated with virus control (Spearman's ρ = -0.51; p = 0.05). Thus, our analysis identified the early cumulative suppressive capacity of CD8 T-cells as a predictor of natural control. Furthermore, simulating a large virtual population, our model quantified the minimum capacity of this early CD8 T-cell response necessary for long-term control. Our study presents new, quantitative insights into the role of CD8 T-cells in the natural control of HIV infection and has implications for remission strategies.

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.

From conceptualising to modelling structural determinants and interventions in HIV transmission dynamics models: a scoping review and methodological framework for evidence-based analyses.

BACKGROUND: Including structural determinants (e.g. criminalisation, stigma, inequitable gender norms) in dynamic HIV transmission models is important to help quantify their population-level impacts and guide implementation of effective interventions that reduce the burden of HIV and inequalities thereof. However, evidence-based modelling of structural determinants is challenging partly due to a limited understanding of their causal pathways and few empirical estimates of their effects on HIV acquisition and transmission. METHODS: We conducted a scoping review of dynamic HIV transmission modelling studies that evaluated the impacts of structural determinants, published up to August 28, 2023, using Ovid Embase and Medline online databases. We appraised studies on how models represented exposure to structural determinants and causal pathways. Building on this, we developed a new methodological framework and recommendations to support the incorporation of structural determinants in transmission dynamics models and their analyses. We discuss the data and analyses that could strengthen the evidence used to inform these models. RESULTS: We identified 17 HIV modelling studies that represented structural determinants and/or interventions, including incarceration of people who inject drugs (number of studies [n] = 5), violence against women (n = 3), HIV stigma (n = 1), and housing instability (n = 1), among others (n = 7). Most studies (n = 10) modelled exposures dynamically. Almost half (8/17 studies) represented multiple exposure histories (e.g. current, recent, non-recent exposure). Structural determinants were often assumed to influence HIV indirectly by influencing mediators such as contact patterns, condom use, and antiretroviral therapy use. However, causal pathways' assumptions were sometimes simple, with few mediators explicitly represented in the model, and largely based on cross-sectional associations. Although most studies calibrated models using HIV epidemiological data, less than half (7/17) also fitted or cross-validated to data on the prevalence, frequency, or effects of exposure to structural determinants. CONCLUSIONS: Mathematical models can play a crucial role in elucidating the population-level impacts of structural determinants and interventions on HIV. We recommend the next generation of models reflect exposure to structural determinants dynamically and mechanistically, and reproduce the key causal pathways, based on longitudinal evidence of links between structural determinants, mediators, and HIV. This would improve the validity and usefulness of predictions of the impacts of structural determinants and interventions.

Expert Consensus Statement on an Updated Definition of Unintended Weight Loss Among Persons With Human Immunodeficiency Virus in the Modern Treatment Era.

The era of modern antiretroviral therapy (ART) has markedly improved health and survival among persons with human immunodeficiency virus (HIV) (PWH). In the pre-ART era, wasting was associated with HIV disease progression to acquired immunodeficiency syndrome and death. Effective ART has reduced the prevalence and incidence of this pre-ART form of HIV-associated wasting. However, a subgroup of ART-treated virally suppressed PWH continue to lose weight, often accompanied by aging-related comorbidities and/or functional deficits. For this subgroup of patients, the older definition of HIV-associated wasting (HIVAW) cannot and should not be applied. An expert panel comprising the authors of this white paper convened to review the existing definition of HIVAW and to create an updated definition that they termed HIV-associated weight loss, based on clinically defined parameters among contemporary PWH receiving ART. Here, clinical features and laboratory biomarkers associated with HIV-associated weight loss are reviewed and approaches to screening and treatment are considered. Available management approaches, including the use of current US Food and Drug Administration-approved medications for HIVAW and other available therapies are discussed. The expert panel also identified knowledge gaps and provided recommendations for clinicians, payers, and researchers.