Fundación Huésped is a nonprofit foundation in Argentina. It was created in 1989 for the purpose of fighting HIV/AIDS, with a specific focus on creating a social environment that would allow the disease to be overcome. Since October 2015, the foundation has maintained a free testing center which allows rapid diagnosis of HIV/AIDS.
High-quality, widely accessible international longitudinal cohort data for people living with HIV (PWH) have long been needed for advancing open science and data-driven innovation, yet stringent and incongruent privacy regulations have made data sharing difficult. Synthetic data generation offers a promising privacy-preserving alternative, but producing realistic synthetic cohorts of PWH remains challenging due to complex temporal dynamics, interdependent clinical variables, long follow-up periods, and high missingness inherent in such data. Here, we introduce Medical Longitudinal latent Diffusion (MeLD), a generative model designed to synthesize variable-length, decades-spanning, mixed-type clinical trajectories with missingness. Using the Caribbean, Central, and South America Network for HIV Epidemiology (CCASAnet) cohort, one of the world's largest international HIV datasets with over 30 years of follow-up on nearly 50,000 PWH, we show that MeLD consistently outperforms state-of-the-art methods across data utility, fidelity, and privacy. Notably, MeLD excels in longitudinal inference utility, accurately reproducing time-to-death estimates and risk factor effects, while maintaining strong privacy protection. This work delivers the first in-depth, large-scale, and openly accessible synthetic longitudinal cohort of PWH that faithfully preserves the distributional patterns and clinical associations observed in real data, offering an immediately deployable resource for hypothesis generation, methods innovation, medical training, and reproducible HIV research.
BACKGROUND:There is a concern about the potential increased risk of acquiring HIV infection after vaccination with adenovirus type 5 (Ad5) vector-based vaccines. We aimed to investigate whether Ad5-nCoV increases the risk of HIV infection. METHODS:Between September 2020 and March 2021, a Phase 3 clinical trial was executed to evaluate the efficacy of Ad5-nCoV. This trial, employing a double-blind, randomized, and placebo-controlled design, enrolled 44,247 participants from 66 clinical sites spanning Argentina, Chile, Mexico, Russia, and Pakistan. Participants were allocated randomly in a 1:1 ratio to receive either Ad5-nCoV or a placebo, and their HIV-negative status was assessed by self-report and confirmed by HIV testing on a baseline blood sample at the end of the study. Consequently, individuals initially administered a placebo received one dose of Ad5-nCoV, while those initially given Ad5-nCoV finally received two doses, with an interval of approximately 6-10 months between administrations. The trial design and primary outcomes have been previously reported. This analysis involves a comprehensive assessment of the associations between pre-existing Ad5 neutralizing antibodies, HIV prevalence and incidence before and after vaccination while accounting for demographic variables. RESULTS:A total of 43,780 participants who had valid HIV baseline testing results were included in this study. Prior to vaccination, there was no discernible difference in HIV prevalence between the placebo group (0·39% of 21,877 participants) and the Ad5-nCoV group (0·38% of 21,893 participants). This similarity persisted when the data were stratified by country, gender, age, and race. Paired analyses assessing HIV incidence were conducted on participants who tested negative for HIV before vaccination, with data collected over a 6-month period post-vaccination. The results revealed notable similarity in HIV incidence across all groups: 0·29% for Group A (Ad5-nCoV group), 0·21% for Group B (Placebo group), 0·27% for group A + D (Ad5-nCoV group and 1 × Placebo+1 × Ad5-nCoV group), 0·1% for Group C (2 × Ad5-nCoV group), and 0·25% for Group A + C + D (participants who received at least one dose of Ad5-nCoV). Testing approximately 100 randomly chosen participants in each country revealed a similar distribution of pre-existing Ad5 neutralizing antibodies (Nab), with the ratio above a titer of 200 ranged from 65·42% to 67·71%. Notably, the heightened presence of pre-existing Ad5 Nab did not result in an increased risk of HIV infection. CONCLUSION:The Ad5-nCoV did not increase the short-term risk of HIV infection in this large and diverse sample of the general population, regardless of the presence of pre-existing Ad5 Nab providing valuable insights into the safety of Ad5 vector-based vaccines. CLINICALTRIALS:gov, NCT04526990.
BACKGROUND:Antiretroviral therapies with long dosing intervals have the potential to improve virological outcomes and treatment satisfaction for people with HIV-1. We report the primary endpoint results from week 48 of ISLEND-2, a phase 3 trial evaluating the efficacy and safety of switching to once-weekly oral islatravir-lenacapavir from daily oral standard of care in virologically suppressed adults with HIV-1. METHODS:This randomised, open-label, active-controlled, phase 3 non-inferiority trial was conducted at 100 sites in 14 countries and territories. Eligible participants were adults (aged ≥18 years) with HIV-1 who had been virologically suppressed on daily oral standard-of-care treatment for at least 6 months and had no previous virological failure. Participants were randomly assigned (1:1), using interactive response technology and stratified by geographical region, antiretroviral class, and CD4+ T-cell count, to switch to the once-weekly, single-tablet oral regimen of islatravir (2 mg)-lenacapavir (300 mg) or to continue daily oral standard of care for at least 96 weeks. The primary endpoint was the proportion of participants with an HIV-1 RNA viral load of 50 copies per mL or higher at week 48 (as per the US Food and Drug Administration-defined Snapshot algorithm), with a non-inferiority margin of 4%, assessed in all randomly assigned participants who received any dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT06630299, and is active but closed to new participants. FINDINGS:From Oct 8, 2024, to April 30, 2025, 727 participants were screened, of whom 647 were eligible for the study, 634 were randomly assigned, and 626 received treatment: 314 with islatravir-lenacapavir and 312 with standard of care. Of 626 participants, 211 (34%) were female, 193 (31%) were Black, 119 (19%) were Asian, 123 (20%) were Hispanic or Latine, and 89 (14%) were aged 65 years or older. At baseline, 552 (88%) were on a single-tablet antiretroviral regimen and 478 (76%) were receiving regimens containing integrase strand transfer inhibitors. At week 48, one (0·3%) of 314 participants in the islatravir-lenacapavir group and four (1·3%) of 312 participants in the standard-of-care group had an HIV-1 RNA viral load of 50 copies per mL or higher (difference -1·0% [95·002% CI -3·0 to 1·1]), meeting the non-inferiority criteria. Treatment-related adverse events occurred in 58 (18%) of 314 participants in the islatravir-lenacapavir group and one (<1%) of 312 participants in the standard-of-care group. Two (1%) of 314 participants in the islatravir-lenacapavir group and one (<1%) of 312 participants in the standard-of-care group discontinued the study owing to adverse events, with adverse events of grade 3 or higher occurring in 24 (8%) and 28 (9%) participants and serious adverse events in 22 (7%) and 27 (9%) participants in the islatravir-lenacapavir group and standard-of-care group, respectively. There were three deaths: one in the islatravir-lenacapavir group and two in the standard-of-care group, none of which were considered treatment-related. INTERPRETATION:Once-weekly islatravir-lenacapavir showed non-inferior efficacy to the standard of care and was generally well tolerated. Longer-term safety data will provide further valuable insights beyond the week 48 data presented here. Islatravir-lenacapavir has potential to be the first once-weekly complete oral single-tablet regimen for HIV-1 treatment. FUNDING:Gilead Sciences and Merck Sharp & Dohme.
Digital health technologies, including machine learning (ML), are transforming infectious disease management, however ML models for HIV care have been limited by data sharing restrictions that prevent multi-site collaboration. Federated Learning (FL) offers a privacy-preserving solution, enabling cross-site model training without sharing patient-level data. We evaluated FL for developing clinical prediction models using data from 22,234 people living with HIV (PLWH) across six sites in five countries within the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet). Across four prediction tasks - 1-year mortality, 3-year mortality, tuberculosis incidence, and AIDS-defining cancer incidence - FL algorithms achieved near-centralized performance while substantially outperforming site-specific models. Performance gains varied across sites, driven by both site size and between-site heterogeneity. Local fine-tuning often improved FL performance, though benefits were task dependent. These findings support FL as a scalable, privacy-preserving infrastructure for multi-site ML in international HIV research.
BACKGROUND:Prevention, screening, and diagnostic services for hepatitis B virus (HBV) and hepatitis C virus (HCV) can prevent morbidity and mortality in people receiving HIV care. However, there is limited information about the availability of HBV and HCV services at HIV clinics globally. METHODS:The International epidemiology Databases to Evaluate AIDS (IeDEA) conducted surveys of service delivery and practices at participating HIV treatment centers from 7 regions. We used 2023 survey data to measure availability of HBV vaccination, HBV and HCV screening, HBV surface antigen (HBsAg), HBV DNA, HCV antibody, and HCV RNA testing. Multivariable logistic regression models were used to test associations of site characteristics with HBV and HCV services. RESULTS:HBV vaccination was available on-site at 67.7% of 204 HIV treatment sites. Screening for HBV and HCV at HIV care enrollment was reported by 72.1% and 50% of sites, respectively. HBsAg, HBV DNA, HCV antibody, and HCV RNA testing were available on-site at 77%, 47.6%, 61.8%, and 44.6% of sites, respectively. Sites serving predominately rural (vs. urban) populations were less likely to report on-site availability of HBV DNA [odds ratio (OR):0.07; 95% confidence interval: 0.01 to 0.68; P = 0.02], HCV antibody (OR = 0.18; 95% CI: 0.04 to 0.92; P = 0.04), and HCV RNA (OR = 0.10; 95% CI: 0.01 to 0.90; P = 0.04) testing. CONCLUSION:Life-saving services such as HBV vaccination, HBsAg, and HCV antibody testing were available on-site at most HIV treatment sites participating in the IeDEA network. Lower availability at rural sites suggests that expansion of services is important to eliminate HBV and HCV as public health problems in people receiving HIV care.
