AIDS

Introduction Viet Nam has achieved one of the fastest declines in new HIV infections in the WHO Western Pacific Region. In 2020, the Government launched the National Strategy to End the AIDS Epidemic by 2030. At its midpoint in 2025, a national epidemiological and programmatic review was undertaken to assess the countrys progress and remaining challenges. Methods We conducted a review of the national HIV surveillance and programme data and the Joint United Nations Programme on HIV/AIDS database, focusing on four components: disease burden, prevention, testing, and treatment programmes. Results Estimated annual new HIV infections among adults declined from 14,000 (2010) to 6,117 (2024), a 57% reduction, while the number of PLHIV stabilised at 267,455 in 2024. The epidemic has shifted from being mainly among people who inject drugs (PWID) in the 1990s and early 2000s to being increasingly concentrated among men who have sex with men (MSM) and transgender people (TG), who accounted for 58% of new infections in 2024. In 2024, 88% of people living with HIV (PLHIV) knew their status, 79% of those diagnosed received antiretroviral therapy (ART), and 96% of people on ART achieved viral suppression. Harm reduction outcomes were strong, with opioid substitution therapy (OST) coverage around 40% since 2020 and safe injecting practices among PWID above 90% over the last ten years. The pre-exposure prophylaxis programme expanded rapidly in recent years, reaching 17.4% of the MSM. HIV testing volume was 3.4 million in 2024, with an increasing number of confirmatory testing laboratories. HIV status awareness in 2024 was below the 80% national target for sex workers (59.0%), PWID (62.5%), and MSM (79.2%), but exceeded the target for TG (94.1%). The high rate of viral load suppression indicates strong adherence and reflects the overall quality of treatment services. Conclusions Viet Nams progress reflects two decades of sustained harm reduction among people who inject drugs, early adoption of community-led and decentralised HIV testing innovations, rapid scale-up of PrEP, and consistently high viral suppression among people on ART. These combined system and community-based approaches offer transferable lessons for other low- and middle-income countries.

Importance: The immune mechanisms driving vascular disease remain incompletely understood. People with HIV (PWH), even during effective antiretroviral therapy (ART), exhibit persistent immune activation and inflammation, which may contribute to higher rates of vascular disease and mortality compared with people without HIV (PWoH). Leveraging a cohort of U.S. military personnel followed from HIV diagnosis through long-term ART suppression, we sought to identify immunologic pathways underlying increased vascular risk. Objective: To identify plasma biomarkers reflecting distinct immune mechanisms that predict incident vascular outcomes in ART-suppressed PWH. Design: Case-cohort study within the U.S. Military HIV Natural History Study. Setting: Longitudinal, multicenter observational cohort. Participants: A total of 1,002 ART-suppressed PWH (HIV RNA <50 copies/mL) were included, with N=135 vascular event (VE) cases and N=702 controls. Cases encompassed atherosclerotic cardiovascular disease (ASCVD) - coronary artery disease (CAD), myocardial infarction (MI), stroke (CVA), peripheral artery disease (PAD) - and venous thrombotic events (VTE) - deep vein thrombosis (DVT) and pulmonary embolism (PE). Exposures: Thirty-three soluble plasma analytes quantified using a high-sensitivity multiplex assay from samples collected [&ge;]1 year after ART suppression. Main Outcomes and Measures: The primary outcome was incident ASCVD. Associations between cytokine concentrations (individual and clustered) and vascular risk were evaluated using unsupervised clustering, Cox proportional hazards models, and causal inference (to estimate 5-year ASCVD risk under hypothetical cytokine alterations). Mediation analyses assessed direct and indirect effects of key inter-related cytokines. Secondary outcome included any VE (ASCVD plus VTE). Covariates included traditional cardiovascular risk factors, HIV clinical variables, and demographics. False discovery rate (FDR) adjustment was applied using the Benjamini-Hochberg method. Results: Cytokine clusters reflecting NLRP3 inflammasome activation and persistent inflammation (IL-18, IL-6) and individual markers (IL-18: HR=1.89, q=0.007; TGF-{beta}2: HR=0.74, q=0.026) were associated with increased ASCVD risk. IL-18 remained nominally significant after adjusting for traditional risk factors (p<0.05) but did not meet FDR significance (q<0.05). Conclusions and Relevance: NLRP3 inflammasome activation and reduced TGF-{beta}2, indicating loss of anti-inflammatory and repair mechanisms, may contribute to atherogenesis in ART-suppressed PWH. These findings highlight potential interventional targets for mitigating inflammation-driven vascular risk and warrant validation in larger cohorts to inform novel therapeutic strategies.

Background: The HIV reservoir is established within days of infection and persists despite antiretroviral therapy (ART). However, data describing early reservoir decay dynamics and the host immune responses associated with this process remain limited. Methods: We analyzed more than 500 longitudinal blood samples from 67 individuals treated during acute HIV infection. Plasma cytokines and HIV reservoir size (intact and defective DNA) were quantified. Associations between immune markers and reservoir decay following ART initiation were assessed using unsupervised clustering, mixed-effects linear spline models, and nonlinear modeling. Results: Higher levels of IFN-{gamma}, IL-10, IL-18, and TNF- during weeks 24-52 of ART were associated with significantly faster decay of both intact and defective HIV DNA. These relationships were independent of ART initiation timing (days since infection), baseline viremia, initial CD4+ T cell count, and longitudinal CD4:CD8 ratio. Among these cytokines, IL-10 demonstrated the strongest association with accelerated reservoir decay, despite prior evidence linking it to larger reservoirs in SIV models. Discussion: These findings highlight the pleiotropic and stage-dependent roles of cytokines across acute to later stages of HIV, suggesting that a coordinated balance between immune activation and regulation of inflammation may promote early HIV reservoir decay.

Background: HIV/HBV coinfection is associated with substantial liver-related morbidity and mortality, yet the impact of social vulnerability (SV) on clinical outcomes has not been systematically assessed. We evaluated associations of multidimensional SV with mortality, hepatic, virologic, and extrahepatic organ outcomes among adults with HIV/HBV. Methods: We conducted a retrospective cohort study using TriNetX data from 110 U.S. healthcare organizations (2010-2026). We propensity score matched adults with HIV/HBV with and without documented SV 1:1 (2,024 per group). SV was defined using a four-domain framework encompassing material, healthcare access and engagement, interpersonal, and psychosocial vulnerability. Results: Over 15,900 person-years, SV was associated with higher mortality (hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.72-2.47), liver composite events (HR, 1.37; 95% CI, 1.07-1.76), hepatic decompensation (HR, 1.94; 95% CI, 1.39-2.70), hepatic failure (HR, 2.39; 95% CI, 1.53-3.73), HBV viremia (HR, 1.69; 95% CI, 1.32-2.16), and HIV viremia (HR, 2.05; 95% CI, 1.71-2.46). SV was also associated with major adverse cardiovascular events (HR, 1.47), chronic kidney disease (HR, 1.49), and diabetes (HR, 1.25). Multidomain SV generally showed stronger associations than single-domain SV for most hepatic and virologic outcomes, with HR ranges of 1.76-2.62 versus 1.35-1.76 for single-domain SV. Healthcare access and engagement vulnerability was most consistently associated with mortality and hepatic outcomes. Conclusions: SV was associated with mortality, hepatic disease, impaired HIV/HBV control, extrahepatic organ morbidity, and acute care utilization in adults with HIV/HBV. SV assessment may improve risk stratification and identify actionable intervention targets during HIV/HBV care.

Abstract Background: In resource-rich regions, such as the U.S. and Europe, the incidence of Kaposi sarcoma (KS) amongst persons living with HIV (PWH) has dramatically declined with the advent of combination antiretroviral therapy (ART). In contrast, in low- and middle-income countries (LMICs), much less is known, particularly since the World Health Organization's recommendation in late 2015 to use ART in all PWH. We take advantage of the coincident electronic clinical data capture at HIV care facilities to estimate the incidence of KS among PWH in care with ready access to ART, piloting a data validation approach to address errors in these routine clinic data. Methods: We evaluated PWH enrolled from January 2010 to December 2019 in 13 HIV care clinics in 8 countries participating in the East Africa (EA-IeDEA) and Caribbean, Central and South America (CCASAnet) regions of the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium. Selected measurements were validated via chart review on a subset of PWH, and we estimated KS incidence in both unvalidated and validated data via generalized raking techniques. Results: A total of 235,474 PWH from EA-IeDEA and 19,683 from CCASAnet gave rise to 719 and 103 incident cases of KS, respectively. A total of 824 eligible records were validated. ART use was substantially lower in EA-IeDEA than CCASAnet in 2010 but equalized by 2019. From 2010 to 2019, KS incidence decreased on average 21% per year (incidence rate ratio [IRR] 0.79; 95% CI 0.75-0.82) in EA-IeDEA but only 6% (IRR=0.94; 95% CI 0.83-1.06) in CCASAnet. Conclusions: Among PWH attending HIV care facilities in East Africa, we observed a trend suggesting a reduction in KS incidence that paralleled increased Treat All era ART use in these clinics. In the Caribbean, Central and South America, there was hardly a change in the incidence, despite high-frequency ART use in the region as well.

Background: Misclassification of HIV status in population-based surveys remains a critical barrier to accurate surveillance and program evaluation. Self-reported HIV status may diverge from objective measures, particularly among individuals receiving antiretroviral therapy (ART). We used biomarker-confirmed antiretroviral (ARV) drug detection to assess the prevalence and correlates of discordance between self-reported HIV status and biologic evidence of HIV treatment among people living with HIV (PLHIV) in Zambia and South Africa. Methods: We conducted a secondary analysis of the HPTN 071 (PopART) cluster-randomized trial. At the 24-month survey visit, participants underwent HIV testing and laboratory assessment for ARV drugs in plasma. We defined discordant self-report (hereafter "non-disclosure") as reporting HIV-negative or unknown status among individuals with ARV drugs detected. We estimated the prevalence of non-disclosure, compared prevalence by study arm, and used modified Poisson regression to identify associated factors. We also examined whether non-disclosure was associated with viral suppression (<400 copies/mL). Results: Among 3,240 PLHIV with ARV drugs detected, 552 (17.0%) did not report an HIV-positive status--indicating that nearly one in six individuals on ART were misclassified by self-report. Non-disclosure did not differ between intervention and control arms (adjusted relative risk [aRR]: 1.03; 95% CI: 0.67-1.58). Non-disclosure was more common among younger individuals (age 18-24 years: aRR 2.30; 95% CI: 1.66-3.19), men (aRR: 1.39; 95% CI: 1.07-1.79), and those in formal employment (aRR: 1.42; 95% CI: 1.06-1.90). Individuals reporting condomless sex at last encounter were also more likely not to disclose (aRR: 1.59; 95% CI: 1.31-1.92). Viral suppression was high overall (93.7%) and did not differ by disclosure status (aRR: 1.06; 95% CI: 0.74-1.52). Conclusion: A substantial proportion of PLHIV receiving ART did not report a known HIV-positive status, highlighting important discordance between biomarker evidence and self-reported data. Despite high levels of viral suppression, these individuals remain "hidden" from routine surveillance, with implications for estimating HIV diagnosis and treatment coverage. Strategies that incorporate objective measures alongside self-report, and that address social and structural barriers to disclosure, are essential to improve the accuracy of HIV surveillance and guide effective public health responses.

People living with HIV-1 (PWH) receiving antiretroviral therapy (ART) exhibit an increased cardiovascular disease (CVD) risk. Coronary atherosclerotic plaque formation is linked to chronic immune activation, a process fueled in PWH by additional mechanisms likely including residual HIV-1 production and microbial translocation from the gut during ART. Our previous studies demonstrated that aldehyde dehydrogenase (ALDH), an enzyme converting vitamin A into retinoic acid (RA), is upregulated in myeloid cells upon exposure to viral/bacterial/fungal products and that RA promotes HIV-1 production. To explore the link between ALDH/RA pathway and CVD risk, we used PBMC/plasma from ART-treated PWH (PWH+ART; n=51) and people without HIV-1 (Pw/oH; n=63) from the Canadian HIV/Aging Cohort Study, with/without subclinical coronary atherosclerosis, measured by coronary computed tomography angiography. ALDH expression was analyzed by flow cytometry on monocyte subsets, dendritic cells, and CD4+ T-cells. Unsupervised t-SNE-guided FlowSOM analysis associated top ALDH activity with a monocyte phenotype. The frequency of ALDH+ monocytes and plasma levels of RA and retinol binding protein 4 were increased in PWH+ART versus Pw/oH, with the highest RA levels coinciding with detectable plasma levels of soluble HIV-1 gp120. Multivariate regression models linked ALDH activity in monocytes to subclinical coronary atherosclerosis (i.e., total plaque volume, low attenuated plaque volume, coronary artery calcification score) presence/burden in PWH+ART, independently of Framingham risk score. Finally, ALDH+ monocyte frequency and RA levels positively correlated with pericoronary fat attenuation index, an emerging CVD predictor. Thus, ALDH/RA pathway may represent a new marker of metabolic/immune dysfunction contributing to CVD risk in ART-treated PWH.

Abstract Background: HIV self-testing (HIVST) has been promoted as a strategy to reach individuals who do not access facility-based testing. However, evidence on whether HIVST leads to more frequent testing among women of reproductive age in Uganda remains limited. This study evaluated the impact of HIV self-testing on recent HIV testing among women using nationally representative data. Methods: Data were drawn from the 2022 Uganda Demographic and Health Survey (UDHS), including 6,438 women aged 15-49 years. The primary outcome was recent HIV testing, defined as having tested for HIV within the 12 months preceding the survey. The treatment variable was ever having used HIV self-testing. Propensity score matching (PSM) with 1:1 nearest neighbour matching (caliper = 0.05) was used to balance observed covariates including parity, media exposure, education, residence, wealth quintile, health insurance, and age group. The average treatment effect on the treated (ATT) was estimated. Results: Among 6,438 women, 23.87% (1,537) reported ever using HIV self-testing. Recent HIV testing was observed in 67.4% of HIVST users compared to 47.4% of non-users (unmatched difference = 20%). After matching, HIVST use increased the likelihood of recent testing by 15.6 percent (ATT = 15.6%; SE = 0.052; t = 2.99). Covariate balance was achieved post-matching, with mean bias reduced from 20.5% to 0.7%, and the B statistic falling from 50.4% to 2.5% (below the 25% threshold). All standardized differences were substantially reduced, with education showing perfect balance (100% reduction) and wealth showing 97.6% reduction. Conclusion: HIV self-testing significantly increases recent HIV testing among women of reproductive age in Uganda. Expanding access to HIVST, particularly for women with lower education, those in poorer wealth quintiles, and those without media exposure, could improve testing frequency and support progress toward the UNAIDS 95-95-95 targets.

Background. In Japan, lifelong antiretroviral therapy (ART) is funded through the physical disability (immune dysfunction) certification pathway, which requires two laboratory assessments four weeks or more apart. This statutory pathway, rather than clinical need, contributes to a median diagnosis-to-ART interval of about 42 days. We evaluated relaxing or reforming it to permit immediate ART. Methods. We developed a stochastic individual-based microsimulation of HIV in Japan, linked to a payer-perspective cost-effectiveness analysis over a 40-year horizon after a 20-year burn-in, calibrated to national surveillance and cascade data. We compared immediate ART with one-month (primary) and two-month (secondary) delays. Costs and quality-adjusted life-years (QALYs) were discounted at 2% per year; uncertainty was assessed across 200 seeds and by probabilistic and one-way sensitivity analyses. Findings. Against the one-month delay, immediate ART averted 2,991 infections and 1,761 deaths among people with HIV over 40 years, gained 9,071 QALYs, and reduced discounted costs by JPY 54.4 billion (net monetary benefit JPY 99.7 billion). The two-month comparison saved JPY 82.5 billion (4,535 infections, 2,688 deaths averted). Immediate ART was dominant at the base case and in all 1,000 probabilistic sensitivity-analysis iterations; cumulative savings offset the early investment within 11 to 12 years, and sensitivity analyses altered only its magnitude. Interpretation. Permitting immediate ART by reforming the certification pathway was projected to reduce HIV incidence, improve population health, and save public-payer costs within the second decade, supporting consideration of statutory reform.

Intravital imaging studies of HIV-1-infected humanized mice by three independent groups revealed the presence of small T cell syncytia. Although these multinucleated entities represent only a small fraction of infected T lymphocytes, they arise at the earliest stages of infection, are highly motile, and they make frequent contact with potential target cells. Importantly, while such transient contacts allow for virus transfer, they typically do not result in fusion and these exclusively T cell-based syncytia thus do not grow beyond the three- or four-nuclei stage. Immunofluorescence microscopy analyses, together with initial multiparameter flow cytometric evaluation and proteomic profiling by our lab and collaborators, identified these small T cell syncytia (henceforth referred to merely as syncytia) as a distinct subpopulation of infected cells. Because they appear as soon as any infected cells are detectable and thus likely contribute to early viral spread, they also trigger innate immune responses, including attacks by cytolytic effectors such as natural killer (NK) cells. Here, we first introduce a newly developed surface split GFP system which allows to unequivocally distinguish syncytia from infected mononucleated cells, and which also enables isolating these entities for in-depth functional analyses. Then, using multiparameter flow cytometry with UMAP clustering and transcriptomic profiling, we document that syncytia represent a subpopulation of infected cells that do indeed clearly differ from both uninfected and infected mononucleated T lymphocytes, particularly also regarding expression of immune-regulatory host factors. Finally, we show that the rate of direct killing by NK cells is substantially higher for syncytia than for infected mononucleated cells, both in 2D suspension co-culture and in a 3D collagen coculture system. While the fitness costs imposed on syncytia by such increased susceptibility to NK cytolysis during early infection might be compensated for by yet to be determined syncytia functions that (directly) enhance virus spread, we note that irrespective of what such virus spread-enhancing functions may be, the increased vulnerability of syncytia could possibly be exploited for the development of novel antiviral strategies.

Across 30 US states and the District of Columbia, eliminating the AIDS Drug Assistance Program is projected to save $6.45 billion in direct costs while generating $14.89 billion in downstream HIV care costs attributable to excess incident infections from 2026-2035. Costs are projected to surpass savings within six years.

Background: HIV prevalence among female sex workers in Benin has declined steeply over the last thirty years, driven by successful HIV prevention and treatment programming among sex workers and their clients. To maintain progress in an era of constrained funding, HIV prevention programming should be targeted towards those most at risk of HIV seroconversion. We present a model-based approach that produces finely stratified HIV incidence estimates from widely available HIV prevalence data from serial cross-sectional surveys among female sex workers. Methods: We analysed participant-level data from twelve cross-sectional surveys among FSW in Cotonou, Benin from 1993-2022. We created a compartmental model representing women transitioning into and out of sex work and acquiring HIV. The model was stratified by single year of age, duration at-risk, calendar year, and time since HIV seroconversion and calibrated to HIV prevalence by single-year age and duration at-risk, and age and duration distribution data. Results: HIV prevalence among sex workers aged 15-49 in Cotonou declined from 44.9% (95%CI 41.2-48.9) in 1995 to 8.6% (95%CI 6.4-11.8%) in 2022 (Figure 1). HIV incidence declined by 86% (95%CI 82-90%) between 1994 and 2013 from 19.7/100py (95%CI 9.5-26.9) to 2.5/100py (95%CI 1.2-3.5), and remained stable thereafter through 2022 (Figure 2A). Throughout the study period, new infections were concentrated among women who recently started selling sex: in 2022, 72% of infections occurred in the first year of sex work (95%CI 64-81%; Figure 2B). Incidence patterns by age varied less than by duration and was similar at around 1.5/100py for all sex workers under age 30, rising to 4/100py among those over age 40. Modelled incidence exceeded empirical cohort estimates, highlighting sensitivity to assumptions about HIV prevalence at sex work initiation, episodic sex work, duration misclassification, and population size. Conclusion: We estimated large declines in HIV incidence among sex workers in Benin from 1994-2013, but slower progress from 2013-2022. New sex workers across all age groups, who may be weakly linked to programmes, should be the highest priority for HIV prevention interventions and community outreach efforts. This modelling approach to empirically monitor incidence among sex workers should be applied across high burden epidemic settings with serial survey data to guide prevention efforts, including the allocation of limited provision of long-acting pre-exposure prophylaxis.

BackgroundHuman immunodeficiency virus type 1 (HIV-1) infection is characterized by progressive immune dysfunction, classically attributed to depletion of CD4{square} T lymphocytes. Despite decades of research, the mechanisms underlying the functional deterioration of cellular immunity remain incompletely understood. We hypothesized that, in addition to quantitative CD4{square} T-cell loss, HIV infection may induce phenotypic reprogramming of CD4{square} T cells, resulting in altered surface-marker expression and impaired immunological function. MethodsPeripheral blood samples were obtained from untreated HIV-positive individuals and healthy controls. Flow cytometric immunophenotyping, recombinant HIV-1 p17 stimulation assays, immunofluorescence imaging, ELISPOT analysis of interferon-{gamma} secretion, and CD4{square}/CD8{square}conjugation assays were performed to investigate dynamic changes in T-cell phenotype and function following viral protein exposure. ResultsHIV-positive samples demonstrated progressive reductions in CD4{square} T-cell counts accompanied by corresponding increases in CD8{square} T-cell populations following p17 stimulation, while the combined CD4{square}/CD8{square} T-cell count remained relatively stable. Immunofluorescence analyses identified cells exhibiting simultaneous CD4- and CD8-associated marker expression after prolonged incubation. Functional analyses further demonstrated markedly reduced interferon-{gamma} secretion in the newly identified cell population compared with conventional CD8{square} T cells. Conjugation assays additionally suggested altered cellular interaction patterns between reprogrammed cells and target CD4{square}lymphocytes. ConclusionsThese findings support the hypothesis that chronic HIV infection may be associated with phenotypic reprogramming of CD4{square} T cells rather than simple quantitative depletion alone. Although the underlying molecular mechanisms remain to be established, this exploratory model provides an alternative framework for investigating HIV-associated immune dysfunction and may stimulate future studies using lineage-tracing, single-cell transcriptomics, and epigenetic profiling to evaluate this proposed mechanism.

People with HIV (PWH) on antiretroviral therapy (ART) experience excess morbidity and mortality from comorbidities including cardiovascular and metabolic disease, yet the biological mechanisms underlying these outcomes in virally suppressed PWH (VS-PWH) remain incompletely understood. We applied high-dimensional targeted plasma metabolomics to quantify 254 small molecules and 750 lipids across 49 classes in viremic PWH (Vi-PWH), VS-PWH, and people without HIV (PWoH), analyzed alongside multiple T cell metrics and plasma cytokine concentrations. Globally, the plasma metabolome of VS-PWH was indistinguishable from PWoH, while Vi-PWH exhibited substantial metabolic disruption characterized by depletion of phosphatidylcholines, sphingomyelins, and hexosylceramides alongside triglyceride accumulation, dysregulation of the tryptophan-kynurenine and arginine-citrulline axes, and elevations in diacetylated polyamines and N4-acetylcytidine. Ordinal trend analysis identified subtle but consistent residual alterations in VS-PWH, particularly within phosphatidylcholine and sphingomyelin classes, that correlated with elevated TNF and reduced CD4+ T cell counts and CD4/CD8 ratio. Together, these findings indicate that residual TNF-associated inflammation and incomplete T cell recovery continue to shape the plasma metabolome in treated HIV, identifying candidate biomarkers for further mechanistic and clinical investigation.

Introduction Globally and in Africa, HIV mortality is reported to have decreased over the years. Cameroon's national mortality rate was 1.7% in 2023, and there exist regional disparities and underreporting. We assessed the mortality and associated factors among People Living with HIV(PLHIV) initiated into HIV care from January 2021 to December 2023 at the Bamenda regional hospital (BRH) Methods A retrospective cohort study was conducted from June 2024 to December 2024 at the BRH. Using a non-probabilistic consecutive sampling technique, 331 newly initiated participants on ART were included. Data was collected from medical records using a questionnaire and analyzed using R software version 4.3.1. A multivariable Cox regression model included variables that showed statistical significance and assessed their relationship with mortality while adjusting for potential confounders. Significant predictors of mortality were identified. Results The mean age of participants was 41.6 {+/-} 11.7 years, and females constituted 57.7%. Opportunistic diseases were present in 19.0% of cases, with tuberculosis (8.2%) being the most common. Key comorbidities included hypertension (8.8%), diabetes (3.9%), and hepatitis B (3.0%). Blood tests showed elevated liver enzymes (ALAT/ASAT: 41.7{+/-}23.6 U/L) and high blood sugar (144.4{+/-}7.4 mg/dL). In contrast, kidney function (Creatinine: 0.9{+/-}0.2 mg/dL) and immune cell counts (Lymphocytes: 1.8{+/-}0.7 x103/L) appeared normal overall. A cumulative mortality rate of 7.6% over three years (approximately 2.5% per year) was observed. Male sex (AHR=7.83, 95% CI:1.44-42.5, p=0.017), opportunistic diseases (AHR=5.66, 95% CI:1.71-18.7, p=0.004), comorbidities (AHR=6.04, 95% CI:2.02-18.1, p=0.001), Abnormal ALAT/ASAT (p=0.005), and WHO clinical stage III (AHR: 1.1, 95%CI: 1.01 -1.5, p < 0.001), were identified as predictors of mortality. Whereas, BMI and ART adherence showed no significance. Conclusion Mortality among PLHIV in this study was associated with advanced disease, opportunistic diseases, commorbidities and abnormal laboratory findings. Strengthening early diagnosis, management of opportunistic infections, and monitoring of clinical and laboratory indicators may help reduce mortality in this population.

HIV/AIDS remains a major global public health challenge, and disparities in HIV testing persist. In 2024, an estimated 87% of people living with HIV were aware of their status, with lower testing coverage among children aged 0-14 years (63%), and among men (84%) compared with women (92%). Romania initiated its national AIDS program in 1995 and quickly progressed in addressing the epidemic; however, HIV testing remains largely concentrated in specialized services, with late diagnosis, missed testing opportunities, and stigma continuing to limit timely identification and linkage to care. This study aimed to understand better HIV testing/screening practices among clinicians in eastern Romania and to identify gaps that could be addressed through medical education. We conducted an analytical cross-sectional study among healthcare providers in the eastern region of Romania to assess whether HIV testing is routinely offered to patients, explore gaps in clinical judgment and perceived responsibility, and identify factors that facilitate HIV testing. A 17-question anonymous survey was distributed via WhatsApp to clinician groups between August 1 and September 30, 2023. Respondents included physicians (71.9%), nurses (28.1%), and other healthcare professionals, working in infectious diseases (36.0%), internal medicine (22.3%), primary care (13.7%), and other specialties, such as obstetrics-gynecology and pediatrics (18.0%). Only 38.1% of respondents reported routinely screening all patients aged 18 years and older for HIV, while 61.9% did not offer regular HIV testing. The most cited reasons for not screening were the perception that HIV testing was not their responsibility and that their department did not require testing (18.1% each). Clinicians working in settings with established policies on HIV confidentiality, non-discrimination, testing, and post-exposure prophylaxis were more likely to offer routine testing. Universal HIV screening remains uncommon among clinicians in eastern Romania. Supportive institutional policies appear to facilitate routine testing and may reduce missed opportunities for early diagnosis. Normalizing HIV testing as part of routine clinical care, in line with the Romanian National Health Strategy 2022-2030, is crucial for enhancing early detection and strengthening prevention efforts through coordinated action among clinicians, public institutions, and civil society.

Objectives: Estimate fertility rate ratios (FRR) of HIV-positive relative to HIV-negative women in sub-Saharan Africa (SSA) by age group, CD4 stage, ART status, and country. Design: Analysis of nationally representative household surveys with HIV serological testing. Methods: We analysed current pregnancy and births in the past three years by HIV status from 72 nationally-representative household surveys in SSA between 2003 and 2017. Spectrum 2018 estimates for the distribution by CD4 stage and ART status were used to infer fertility of women on ART from changes in fertility of all HIV-positive women as ART coverage increased. We allowed regional differences in the age pattern of relative fertility and estimated country-specific random effects. Results: The ratio of fertility in untreated HIV-positive women with CD4 [&ge;]500 to HIV-negative women was 1.6 to 1.8 for age 15-19, relatively similar to 10% times lower for age 20-29, and 15-50% lower above age 30. Among age 15-19, each 15-point increase in percent sexually active reduced relative excess fertility by 24%. Fertility decreased with lower untreated CD4 count stages, consistent with previous estimates. Women on ART >6 months had fertility closer to that of HIV-negative women for ages 15-29, but still 25-40% lower above age 30. There was substantial variation across countries. Conclusions: Fertility differences for HIV-positive women compared to HIV-negative women are smaller than previous estimates, but vary substantially across countries. Recent data suggest fertility of women on ART is greater than that of untreated HIV-positive women, but remains lower than HIV-negative women. This conclusion should be reviewed as new evidence becomes available.

Background: The first six months after antiretroviral therapy (ART) initiation for HIV is a high-risk period for treatment interruptions that may compromise viral suppression (VS). Recent research in South Africa suggests that more than 40% of patients interrupt care for greater than 28 days during the early treatment period. The quantitative association between early treatment interruptions and VS at 6 and 12 months remains unclear. Methods: We enrolled adults (greater than or equal to18 years) initiating ART from 1 January 2018 to 7 November 2024 with at least 14 months followup in South Africas national ART database (TIER.Net) from 24 public sector facilities in four provinces. Engagement in care during months 0-6 and 7-12 was classified as continuous (no interruptions more than 28 days), cyclical (at least one interruption greater than 28 days but returned to care within follow up period), or disengaged (more than 28 days late without return), based on completed and scheduled visit dates. Modified Poisson regression was used to estimate adjusted risk ratios (aRRs) for VS (less than 50 copies/mL), adjusting for age, sex, initiation year, regimen, engagement pattern, and baseline CD4 count. Findings: Among 57,553 participants (66% female; median age 33 years), 49% and 42% were continuously engaged at 6 and 12 months, respectively; 22% and 17% were cyclically engaged at the same time points. 54% of continuously engaged participants achieved 6-month VS compared with 34% of those with cyclical engagement (aRR 1.60 95% CI 1.55-1.64). At 12 months, 56% of continuously engaged individuals and 40% of those cyclically engaged were suppressed (aRR 1.38 95% CI 1.34-1.42). VS was also associated with dolutegravir-based regimens, later ART initiation year, baseline CD4 count greater than 200 cells/uL, female sex, and older age. Interpretation: Even relatively brief treatment interruptions during the first year of ART were associated with substantially lower viral suppression. Preventing early interruptions should remain a programmatic priority to improve treatment outcomes.

Background: In 2019, WHO recommended three consecutive reactive serological test results for HIV diagnosis to reduce false-positive diagnoses. Malawi changed from a two-test to a three-test strategy in 2022 as HIV test positivity declined. We assessed diagnostic performance, implementation fidelity, and costs. Methods: We analysed national HIV testing data from Nov 1, 2022, to Oct 31, 2025. Using observed three-test classifications as the reference standard, we reconstructed classifications under the two-test strategy. We estimated positive predictive value (PPV), implementation fidelity, potential false-positive diagnoses prevented, incremental costs, and time to offset testing costs through avoided antiretroviral therapy expenditure. Results: Among 9,885,599 encounters eligible for implementation-fidelity analysis, 99.98% followed a valid three-test pathway. The diagnostic-performance analysis included 9,862,908 encounters, of which 171,351 (1.7%) were classified HIV-positive and 9,138 (0.09%) were inconclusive. Under the two-test strategy, 1,209 inconclusive encounters with a T1+/T2+/T3- sequence would have been classified as HIV-positive. Retesting and reference-laboratory data indicated that 82.5% of these would subsequently be classified as HIV-negative, corresponding to 997 false-positive diagnoses prevented (10.3 per 100 000 three-test non-positive encounters; 95% CI 9.7-10.9). Retesting within 1-2 weeks was associated with the highest odds of potential false-positive classification (adjusted OR 39.37, 95% CrI 30.63-50.61). The incremental cost was US$471 per false-positive diagnosis averted and was offset within 7.30 years. Conclusions: Malawi's transition to a three-test HIV testing strategy prevented false-positive diagnoses and unnecessary antiretroviral therapy at modest cost, supporting broader adoption of WHO guidance in similar settings. Funding: Gates Foundation.

Background Adolescents and young adults (AYAs) from key and priority populations face persistent challenges with sustained engagement in HIV pre-exposure prophylaxis (PrEP) care. While PrEP initiation has expanded across sub-Saharan Africa, evidence on long-term retention and determinants of disengagement among AYAs remains limited. We examined time to PrEP disengagement and associated factors among AYAs initiating PrEP in eastern Uganda. Methods We conducted a retrospective longitudinal analysis of routinely collected program data for AYAs aged 15-29 years from key and priority populations who initiated PrEP between 2019 and 2025 at Mbale Regional Referral Hospital. Time to PrEP disengagement was assessed using Kaplan-Meier survival analysis and Cox proportional hazards regression. Multivariable models adjusted for sociodemographic, relational, behavioral, and service delivery factors. Sensitivity analyses redefined the time origin to day 91 following PrEP initiation to reflect the programmatic 90-day grace period. Results Among 3,553 AYAs initiating PrEP, the median time to disengagement was 284 days (95% CI: 273-295). The median age was 24 years (interquartile range [IQR]: 20-26). The probability of remaining engaged in PrEP care declined from 60.1% at 90 days to 20.2% at 365 days. Survival patterns differed significantly by population category and sex at birth but not by age group. In adjusted analyses (N = 3,391), knowledge of a partners HIV status (aHR = 2.04; 95% CI: 1.82-2.29) and initiation through community-based services (aHR = 1.42; 95% CI: 1.17-1.72) were associated with faster disengagement. Married participants had lower hazards of disengagement compared with single participants (aHR = 0.69; 95% CI: 0.64-0.76). Reporting an STI syndrome (aHR = 0.42; 95% CI: 0.32-0.55) or recent gender-based violence (aHR = 0.76; 95% CI: 0.60-0.96) was associated with reduced disengagement. Findings were highly consistent in sensitivity analyses using an alternative risk-period definition. Conclusions PrEP disengagement among AYAs occurs rapidly following initiation, with substantial attrition within the first year. Relational factors, service delivery modality, and population-specific vulnerabilities strongly shape retention trajectories. These findings underscore the need for risk-responsive, differentiated PrEP delivery strategies that strengthen partner-based services, integrate STI and GBV screening, and adapt retention support for AYAs in community and facility settings.