Journal of the International AIDS Society

Retention in antiretroviral therapy care remains a major challenge in high-burden settings such as Malawi, where substantial loss to follow up undermines treatment outcomes and long-term epidemic control. Although machine learning models can accurately identify patients at high risk of disengagement, there is limited evidence on how these predictions can be translated into improved retention outcomes in practice. This study addresses this gap by linking machine learning-based risk stratification to the targeted allocation of retention interventions, providing a framework for evaluating their expected impact on ART retention outcomes. We developed a patient-level Monte Carlo simulation model that integrates individual predicted probabilities of loss to follow up from a validated Extreme Gradient Boosting model with intervention effect sizes derived from a meta-analysis of ART retention interventions conducted in sub-Saharan Africa. The study population included 1,705 ART patients receiving care at Lighthouse Trust clinics in Lilongwe, Malawi. Patients were stratified by predicted risk, and the highest-risk group (n = 512) was targeted for intervention. Six interventions were evaluated, including Expert Client support, psychosocial support, two-way text messaging, adherence clubs, community ART groups, and teen clubs, followed by subgroup-specific and combined approaches allocated based on predicted risk. The primary outcome was twelve-month ART retention, estimated over 5,000 simulation iterations. Subgroup and post-simulation analyses were conducted to assess heterogeneity in intervention response. Among patients classified as high risk (n = 512), baseline retention was 44.1%. Individual interventions improved retention to 52.7% with two-way texting (RR = 1.19; p < 0.001) and 55.0% with Expert Client support (RR = 1.25; p < 0.001). A combined intervention package produced larger gains, increasing retention to 64.0% (RR = 1.45; p < 0.001), corresponding to an absolute improvement of 19.9 percentage points. Intervention effects varied across subgroups, with significant improvements observed among newly initiated patients (43.0% to 58.9%; RR = 1.37; p < 0.001) and clinically unstable patients (28.3% to 39.1%; RR = 1.38; p = 0.01), while effects among adolescents were more modest (34.3% to 45.6%; RR = 1.33; p = 0.03). Despite these improvements, 46% of high-risk patients remained hard to retain after receiving multiple interventions. In this subgroup, expected retention increased only marginally from approximately 0.15 at baseline to 0.20 after intervention, with poor outcomes observed among patients who were virally unsuppressed, had depressive symptoms, or were younger. Machine learning-guided targeting of ART retention interventions can substantially improve retention outcomes, particularly when interventions are combined. However, a substantial subgroup of patients remains hard to reach and vulnerable to disengagement, indicating that existing strategies may be insufficient for individuals with complex clinical and psychosocial needs. This study contributes to knowledge by introducing an integrated framework that combines machine learning risk prediction, meta-analytic intervention effects, and patient-level Monte Carlo microsimulation to quantify twelve-month ART retention outcomes under risk-based targeting with subgroup-specific intervention allocation before real-world implementation. These findings highlight the potential of using individual risk to guide the delivery of retention interventions within routine ART programs to enable more efficient, proactive, and patient-centered allocation of retention resources.

Introduction: Differentiated service delivery (DSD) models aim to reduce time healthcare providers spend with DSD clients, increasing time available for non-DSD clients. We measured nurses' time allocation and explored their experiences with DSD models in South Africa. Methods: We conducted time and motion observations and surveyed nurses at 24 public primary healthcare facilities across two SENTINEL study rounds (09/2022-07/2023 and 11/2023-07/2024). We report median time nurses spent by activity, model of care, and interaction type. Log binomial regression investigated factors associated with high direct nurse-client interaction (above median minutes) and extended work-days ([&ge;]9 hours), and estimated adjusted risk ratios (aRR). Survey questions were related to client care, additional time availability, and policy changes post DSD implementation, with key themes presented alongside illustrative quotes. Results: 176 nurses (88% female, median age 44) were observed for 344 working days; of these, 60 (34%) participated in the provider survey. Nurses spent a median of 293 minutes (53% of their work-day) on direct nurse-client interaction, 89 minutes (22%) on client-support or facility-related tasks, and the remainder on other activities including personal breaks. Time spent per client was similar across conventional care clients (11 [IQR: 8-15] minutes) but ranged between 9 (7-13) to 11 (8-15) minutes for DSD clients; number of direct nurse-client interactions did not differ meaningfully. Nurses at facilities with 2,000-3,999 total remaining on ART (TROA) (aRR 1.56, 95% CI: 1.02-2.37) and in urban areas (aRR 1.43, [1.08-1.89]) had more direct nurse-client interactions than those at facilities with <1,999 TROA and in rural areas, respectively. Nurses at facilities with 4,000+ TROA (aRR 2.22, [1.36-3.63]) and those observed in SENTINEL 3.0 (aRR 1.53, [1.13-2.07]) were more likely to work standard or longer workdays than those at lower TROA facilities (<1,999), those in SENTINEL 2.0 and urban areas. Nurses reported DSD models improved client care (90%), freed up time (60%), and changed clinic procedures and policies (60%). Conclusions: While DSD models did not significantly reduce direct nurse-client interaction time, nurses reported improved client care and gained additional time. DSD impact may vary by facility context. As DSD implementation expands, effective time reallocation may enhance facility performance and provider productivity.

Background: Six-month multi-month dispensing (6MMD) of antiretroviral therapy (ART) reduces clinic visit frequency and is associated with improved retention in care. During the COVID-19 pandemic, Zambia offered 6MMD to clients 3 months after ART initiation, rather than 6 months standard requirement. We estimated the effect of early (3<6 months on ART) versus standard (6-12 months) 6MMD enrolment on the rate of treatment interruption. Methods: We emulated a target trial using routinely collected electronic medical records from 12 public health facilities in Zambia. Eligible clients were 15 years and above, initiated ART 01/20-08/22, were WHO stage 1 or 2 at ART initiation, and had more than 21 months of potential follow-up. Treatment interruption was defined as missing a scheduled clinic or pharmacy visit by more than 28 days. We applied a clone-censor-weight approach to reduce immortal time bias. Clones were censored when observed dispensing deviated from their assigned strategy. Inverse probability of censoring weights (IPCW) accounted for informative censoring, while inverse probability of treatment weights (IPTW) balanced measured baseline confounders between strategies. We used weighted pooled logistic regression of person-month data to estimate the odds of treatment interruption between early and standard 6MMD enrollers, including follow-up months to model the monthly baseline risk. Results: A total of 6,142 ART clients met the inclusion criteria. 741 (12.1%) were early 6MMD enrollers, 1,590 (26.1%) standard 6MMD enrollers, and 3,811 (62.0%) eligible clients who never enrolled in 6MMD. During follow-up, 268 treatment interruptions occurred. In the primary analysis, early 6MMD was associated with lower odds of treatment interruption than standard 6MMD OR 0.701 (95% CI 0.51-0.97). The predicted cumulative probability of treatment interruption at 18 months was 6.5% under the early 6MMD strategy and 9.1% under the standard strategy (risk difference: -2.6 percentage points). Conclusions: Enrolment in 6MMD at 3-6 months after ART initiation was associated with lower odds of treatment interruption than standard enrolment at 6-12 months, with a predicted absolute risk difference of -2.6 percentage points at 18 months. We found no evidence that earlier access to 6MMD increases the risk of treatment interruption.

Introduction: Adolescent girls and young women (AGYW) in South Africa face disproportionately high HIV incidence, yet uptake and retention in prevention services remain suboptimal. Behavioural economics approaches, including incentive based models, have shown promise in improving health seeking behaviours among this population. This study evaluated the Eyakho Mo'ghel (EM) programme, a membership based digital rewards initiative implemented by Shout It Now within the DREAMS HIV prevention framework, to assess its impact on HIV prevention and sexual and reproductive health (SRH) service engagement among AGYW. Methods: A retrospective, observational outcome evaluation was conducted across the full programme implementation period (December 2021 to February 2025) in five districts in Gauteng and North West provinces, South Africa. Deidentified clinical and app records for 4,684 EM members were analysed alongside a 1:1 matched comparison group of 4,684 non members drawn from approximately one million records using stratified random sampling. Outcomes included HIV testing, pre exposure prophylaxis (PrEP) uptake and persistence, contraceptive use, gender based violence (GBV) disclosure, and key health indicators. Multivariable logistic and Poisson regression models, adjusted for age and district, were used to examine associations between EM membership, app usage patterns, and outcomes. Results: EM members were over three times more likely to have tested for HIV (OR = 3.16, 95% CI: 2.83 to 3.54) and tested significantly more frequently than non-members. PrEP initiation was also markedly higher among EM members (OR = 3.15, 95% CI: 2.85 to 3.48), and persistence beyond the first dispensation was approximately 67% more likely (OR = 1.67, 95% CI: 1.63 to 1.72). Contraceptive uptake was 75% more likely (OR = 1.75, 95% CI: 1.53 to 2.01), and EM members were 54% more likely to disclose GBV experiences (OR = 1.54, 95% CI: 1.24 to 1.91). Sustained app engagement and cumulative point accumulation were consistently associated with improved outcomes. No significant differences in HIV seroconversion, TB screening, or incident pregnancy were observed. Conclusions: A non-monetary, digitally integrated rewards programme was associated with meaningful improvements in HIV prevention service uptake, PrEP persistence, contraceptive use, and GBV disclosure among AGYW. These findings support the integration of incentive-based digital engagement models within combination HIV prevention frameworks, particularly in resource-constrained settings.

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.

Introduction: Despite major progress in antiretroviral therapy (ART) scale-up, viral suppression (VS) among children living with Human Immunodeficiency Virus (HIV) remains below global targets in Mozambique. Evidence on determinants of virological non-suppression (VNS) in decentralized rural settings is still limited. Objective: This study aimed to analyse factors associated with VNS among children receiving ART in Chokwe District, Gaza Province, Mozambique. Methods: We conducted a retrospective cohort study including children younger than 15 years who initiated ART between 2022 and 2024 in 27 health facilities in Chokwe District. Sociodemographic, clinical, laboratory, and health care data were extracted from paper medical records and electronic databases. VNS was defined as viral load (VL) [&ge;]1,000 copies/mL of blood after at least 6 months of ART initiation. Kaplan-Meier methods and Cox proportional hazards regression models, adjusted for key sociodemographic, clinical, and health care characteristics, were used to identify factors associated with time to VNS. Adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) were estimated.We conducted statistical analyses using the STATA 15 and R 4.5.1 software packages. Results: A total of 285 children were included. At 6 months after ART initiation, 28.2% of children presented VNS, while 23.3% presented VNS at 18 months. In the adjusted analysis for the first 6 months of follow-up each additional year of age at ART initiation was associated with lower risk of VNS, whereas not initiating treatment on the same day of diagnosis increased the risk of VNS. At 18 months of follow-up, age at ART initiation showed evidence of a non-linear association with VNS. Tuberculosis co-infection and undernutrition at 6 months were also associated with a higher risk of VNS. Conclusion: VNS remains frequent among children receiving ART in Chokwe District. Younger age during early follow-up, delayed ART initiation, tuberculosis co-infection, and undernutrition were important determinants of poor virological outcomes. Strengthening early HIV diagnosis, timely ART initiation, integrated management of TB and undernutrition, and age-responsive follow-up strategies may improve long-term virological outcomes among children living with HIV in resource-limited settings.

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.

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.

Introduction: HIV testing and pre-exposure prophylaxis (PrEP) are efficacious HIV prevention strategies, but uptake remains low among Sub-Saharan African men. Peer-delivered approaches may improve engagement. We developed an intervention combining peer-delivered oral HIV self-testing (HIVST) with incentivized peer referral to HIV services and an SMS-based HIV risk assessment among men in eastern Zimbabwe (IMPERATIVE Trial: NCT06370923). We co-adapted the intervention through iterative prototyping (IP) to enhance its acceptability, feasibility, and potential effectiveness. Methods: From November 2023 to June 2024, we implemented a novel IP framework to refine and test the intervention. Four primary distributors (PDs) were trained to deliver HIVSTs to three peers and refer them to clinic services. Peers could become secondary distributors (SDs), obtain HIVSTs from community hubs and distribute them further. Qualitative data were collected alongside intervention testing to adapt the intervention over two iterations. Activities included three forum theatre workshops, one community advisory board meeting, 25 in-depth interviews, four focus group discussions, and eight observational reports involving men, implementers, stakeholders, and advisory board members. Additionally, 20 men completed baseline and one-week follow-up surveys. Quantitative data were analysed descriptively; qualitative data were analysed using thematic analysis. Results: During testing, HIVST uptake was 100% among PDs, 90% among PD-recruited peers, and 63% among SD-recruited peers. Among self-testers, 50% sought confirmatory testing and about one-quarter initiated PrEP (PDs 25%, PD-recruited peers 30%, SD-recruited peers 25%). Participants viewed the intervention positively and anticipated increased HIV testing and PrEP initiation. Four areas for refinement were identified: recruitment, information dissemination, incentives, and socio-cultural factors. Participant recommendations were adopted before randomised controlled trial testing. Conclusion: Peer-delivered HIVST with referral to HIV services shows promise for engaging Zimbabwean men. The IP framework incorporating participant recommendations enhanced intervention design and delivery within the IMPERATIVE trial. This methodology may inform future intervention development in similar settings.

Background: Transition from adolescent to adult HIV care is a critical period for adolescents and young people living with HIV (AYLHIV), marked by increasing responsibility for self-management alongside ongoing psychosocial and developmental challenges. Existing transition interventions have largely focused on biomedical outcomes and have primarily been developed in high-income settings, with limited attention to empowerment and contextual relevance in low- and middle-income countries. This study aimed to develop and assess the feasibility and acceptability of the Empowerment and Personal Transformation (EPT) intervention to support AYLHIV during transition to adult HIV care. Methods: The EPT intervention was developed using qualitative data from in-depth interviews with AYLHIV, caregivers, and healthcare providers, informed by Empowerment Theory and Social Cognitive Theory. The final intervention comprised six modules addressing communication, empowerment, self-regulation, self-concept, resilience, self-management, and emotional processing. The intervention was subsequently implemented among 40 AYLHIV, and feasibility and acceptability were assessed among the 37 participants who completed the intervention using the Feasibility of Intervention Measure and the Acceptability of Intervention Measure. Internal consistency was assessed using Cronbach alpha coefficients. Results: Qualitative findings identified key needs related to communication, confidence, stigma, emotional wellbeing, resilience, self-management, and transition readiness, which informed intervention development. The final EPT intervention integrated psychoeducation, skills building, reflection, peer learning, and experiential activities. The intervention demonstrated high feasibility and acceptability. Mean feasibility and acceptability scores were 18.37 (SD = 2.10) and 18.51 (SD = 2.02), respectively, out of a maximum score of 20. Internal consistency was high for both feasibility ( = 0.86) and acceptability ( = 0.92). More than 94% of participants agreed or strongly agreed that the intervention was feasible, acceptable, and relevant to their needs. Conclusions: The EPT intervention was feasible and acceptable among AYLHIV and addressed psychosocial and behavioral needs identified during transition to adult HIV care. These findings support further evaluation of the intervention's effectiveness in improving transition-related and HIV care outcomes.

Objective: Youth with HIV experience persistent disparities across the HIV care continuum, including low rates of engagement in care and viral suppression. In a recent national survey, youth and young adults, defined by the CDC as ages 13-34, accounted for approximately 20-40% of new HIV diagnoses in the United States. We describe the Intervention for Virological Suppression in Youth with HIV (iVY), a youth-friendly, tailored approach that integrates mental health and substance use support with HIV treatment engagement. Design: This paper describes the development of the intervention used in iVY, which is currently being evaluated in a randomized clinical trial (RCT) using an adaptive treatment strategy. HIV virological suppression is measured via dried blood spot at 16 weeks. Setting: The intervention is delivered fully remotely across California and Florida. Participants: YWH aged 18-29 who are not durably virally suppressed are enrolled and randomized to the intervention or usual care. The RCT will enroll and randomize 200 participants to the intervention (n = 100) versus usual care (n = 100). Intervention Description: iVY includes: (1) tailored brief, weekly video-counseling sessions focused on HIV treatment adherence and engagement, mental health, substance use, and related barriers; and (2) a mobile health application designed to support adherence, resource access, and peer connection. Participants who are not virally suppressed receive an additional 16 weeks of intensified intervention, while responders continue with app-based support. Conclusion: This paper provides a detailed description of a telehealth-based behavioral intervention tailored to the needs of youth with HIV. The intervention offers a scalable model for integrating behavioral health and HIV care to address barriers to treatment engagement in this priority population.

Introduction After U.S. foreign assistance was frozen in January 2025, empirical data on the status of the HIV response has been limited. To better understand the ongoing impacts of changes in U.S. foreign assistance, we launched an open survey to assess disruptions in HIV-related care among clinics and programs in low- and middle-income countries (LMICs). Methods Conducted from August to December 2025, the survey explored U.S. foreign assistance-related disruptions in HIV service delivery, medication availability, laboratory services and clinic operations; whether disruptions were fully resolved at the survey timepoint; and the introduction of clinic mitigation strategies. Data on other impacts of U.S. funding changes were explored through an open-ended question. A convergent mixed-methods design, involving parallel quantitative and qualitative analyses and merging of findings from each, was used to examine the impacts of U.S. funding freezes on HIV-related care. Results We received 158 responses from 38 LMICs, including 30 countries supported by the U.S. President's Emergency Fund for AIDS Relief (PEPFAR) at the beginning of 2025 (n=123 responses) and eight non-PEPFAR countries (n=35 responses). Respondents represented health centers (25%), hospitals (31%), dedicated HIV clinics and drop-in centers (39%), and multi-site programs (4%), with a majority (59%) in the non-governmental/private sector. Overall, 81% reported disruptions in at least one HIV-related service since January 2025 because of changes in U.S. foreign assistance, with most also reporting disruptions in medication availability, laboratory services, and clinic operations. The largest reported disruptions were in the areas of pre-exposure prophylaxis (67%) and HIV testing (63%), along with patient tracing (67%), adherence support (63%) and services to key populations (64%). Disruptions were more prevalent in PEPFAR-supported countries and were more likely to be "not fully resolved" by time of survey completion. Qualitative data highlighted the impact of U.S. foreign assistance disruptions on the erosion of client trust in the health system and strains on staff morale. Conclusions Substantial and sustained disruptions in HIV prevention and care reported by diverse clinics in LMICs reinforce concerns that recent funding shifts could reverse progress in ending the HIV epidemic, particularly for vulnerable and key populations.

Background Clinical trials demonstrated high efficacy of daily and event-driven oral pre-exposure prophylaxis (PrEP) in HIV prevention. Event-driven PrEP involves taking two tablets before and two times one tablet after sexual contact (2-1-1/on-demand). While both are implemented in Dutch clinical practice, evaluating real-world effectiveness requires large-scale data from routine clinical care. This study compared HIV incidence between daily and event-driven PrEP in the Netherlands. Methods We used surveillance data from the Dutch national PrEP program (August 1, 2019-December 31, 2025). Individuals [&ge;]16 years with [&ge;]1 follow-up consultation after PrEP initiation were included; PrEP regimen since last visit was recorded at each visit. Person-time was modeled as time-varying based on the regimen reported at each consultation. HIV incidence rates were calculated per 100 person-years and Cox proportional hazards models estimated hazard ratios between regimens for HIV acquisition, adjusted for sociodemographics, sexual behavior, and history of sexually transmissible infections. Findings 16,469 individuals (15,843 men who have sex with men, 579 transgender and gender diverse persons, 45 women and two men who have sex with women) initiated PrEP and had [&ge;]1 follow-up visit (median follow-up 2.0 years (IQR=0.8-4.0)). Median age was 33 years (IQR=27-44). 49 PrEP users were diagnosed with HIV over 41,092 person-years (IR=0.12/100 py;95%CI=0.09-0.16), of whom 42 event-driven users (IR=0.20/100 py;95%CI=0.15-0.27) and seven daily PrEP users (IR=0.04/100 py;95%CI=0.02-0.07). In multivariable Cox regression, event-driven PrEP use was associated with a higher hazard of HIV acquisition (aHR=7.0;95%CI=3.0-16.4). Interpretation Despite overall low HIV incidence, the incidence rate in the Dutch national PrEP program was seven-fold higher during event-driven PrEP use compared to daily, which may be due to lower adherence. These findings denotes that, in real-world settings, improved person-centered counseling is needed for individuals interested in, or using event-driven PrEP. Research should identify domains and preferred methods of support. Funding None for this study.

Background Urine tenofovir (uTFV) and dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations respectively estimate short- and medium-term adherence to tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART). We evaluated the accuracy of a point-of-care uTFV assay, and associations between uTFV/TFV-DP, and viral load (VL) and retention outcomes within a South African community ART programme. Methods We measured uTFV and DBS TFV-DP concentrations using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We calculated sensitivity and specificity of the point-of-care uTFV assay at the manufacturer-recommended threshold of [&ge;]1,500 ng/mL compared to LC-MS/MS. We assessed associations of the point-of-care uTFV assay, and DBS TFV-DP concentrations with concurrent viraemia, and with retention-in-care by 16 weeks post-enrolment. Results Of 196 adults median age was 44 years, 127 (64.8%) were female, and 191 (97.4%) were receiving TDF. 185 (94.4%) had detectable point-of-care uTFV, which had high sensitivity (99.5%, 95% CI 96.5-100%) and moderate specificity (76.9%, 95% CI 46.0-93.8%) for detecting uTFV [&ge;]1,500 ng/mL. Two participants had concurrent viraemia [&ge;]1,000 copies/mL; of these 50.0% (95% CI 9.4-90.5) had undetectable point-of-care uTFV, and 100% (95% CI 19.7-100) had low TFV-DP <483 fmol/punch. Among participants without viraemia 97.4% (95% CI 93.6-99.0) had detectable uTFV, and 98.1% (95.3-99.6) had high TFV-DP [&ge;]483 fmol/punch. Point-of-care uTFV and DBS TFV-DP were not associated with retention-in-care. Conclusions The point-of-care uTFV assay demonstrated high sensitivity and moderate specificity to detect uTFV. Over 95% of people without viraemia had detectable point-of-care uTFV or high DBS TFV-DP levels respectively, but these were not associated with 16-week retention-in-care.

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.

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.

Objective: In Japan, antiretroviral therapy (ART) for individuals living with human immunodeficiency virus (HIV) is financially supported through the Physical Disability Certification System for Immunological Impairment. However, certification requires multiple laboratory assessments after diagnosis, possibly delaying ART initiation. This study examined the impact of these eligibility requirements on ART initiation using real-world clinical data. Design: Single-center retrospective cohort study. Setting: Nagoya Medical Center, Japan. Subjects, participants: A total of 568 patients who attended their first consultation between 2015 and 2019 were included. Of these, 434 were ART-naive, and 134 had already initiated ART at the first visit. Main outcome measures: ART initiation rate, time to treatment initiation, factors associated with treatment delay, and utilization of the Physical Disability Certificate system. Results: Among the 434 untreated patients, the median time to ART initiation was 42 days. Seven patients (1.6%) did not meet the Grade 4 certification requirements and remained untreated. Overall, 13 of the 568 patients (2.3%) were affected by the certification system, including those importing ART from overseas or using alternative financial support mechanisms. Non-Japanese nationality, lack of health insurance, unstable employment, and low CD4 cell counts were significantly associated with failure to initiate treatment. Among the 134 previously treated patients, 108 (80.5%) had obtained a Physical Disability Certificate. Conclusions: Although relatively few patients were affected, certification requirements may delay ART initiation among socioeconomically vulnerable populations. Further multi-center and cost-effectiveness studies are needed to improve compatibility between long-term financial support systems and rapid ART initiation strategies after diagnosis.

HIV prevention and testing programmes primarily reach people who self-refer or attend routine health services. Higher-risk individuals are missed if they are healthy, under-estimate their risk of infection or under-report sexual risk-behaviours. We assess a new approach to address limitations in existing programmes by targeting HIV services on ''Circumstantial Determinants'' (CDs) of HIV risk - the social circumstances, settings, and norms associated with behaviours that increase risk of HIV acquisition. Data on potential CDs and sexual behaviour were collected in a population survey in Zimbabwe in 2018/19 (N=9141). HIV-negative individuals reporting [&ge;] 1 sexual risk-behaviours were defined as the 'priority population' for HIV prevention. For each sex, six circumstantial determinants were associated with being in the priority population (aOR [&ge;] 1.30; p [&le;] 0.01). Reach and efficiency of CDs (and combinations) were calculated; ROC curve algorithms evaluated their ability to identify priority population membership; and HIV prevention condom cascades were compared between CD-defined priority population subgroups. Example findings include that targeting men at bars and beerhalls could reach 48.5% of the priority population and 25.1% of lower-risk men. These percentages increase to 77.1% and 53.7% if men with poor mental health, no religious affiliation, negative social capital, or living on agricultural estates are also targeted. Targeting women with poor mental health could reach 32.0% of the priority population and 21.3% of lower-risk women. Targeting additional circumstantial determinants increases these percentages to 54.1% and 37.5%, respectively. Cascade barriers to condom use differed between CD-defined subgroups. The Circumstantial Determinants approach demonstrates proof-of-concept potential to strengthen HIV prevention services.

Introduction: Adolescents living with HIV (ALWH) face disproportionately high rates of depression and anxiety, which can negatively affect antiretroviral adherence, viral suppression, and overall health outcomes. Despite the close relationship between mental wellness and HIV care, mental health services remain inadequately integrated into HIV programs, particularly in low- and middle-income countries. To address this gap, we developed EVA (Educaci&oacuten, Vinculaci&oacuten y Autoayuda), a mental health chatbot co-designed with ALWH to provide psychoeducation on depression and anxiety, teach self-help skills, and facilitate linkage to mental health resources. We evaluated EVA's preliminary impact on depression knowledge and its feasibility and acceptability among ALWH in Lima, Peru. Methods: During January - August 2024, ALWH in Lima, Peru completed baseline assessments, engaged independently with EVA for 20 minutes, and completed endline measures. The primary outcome was change in depression knowledge measured using the Adolescent Depression Knowledge Questionnaire (ADKQ). Secondary outcomes included acceptability, appropriateness, feasibility, intention to use and recommend the chatbot, and satisfaction with the chatbot's features and content. Paired-samples t- tests were used to evaluate pre-post changes in depression knowledge. Results: Fifty ALWH aged 11 - 19 years participated, among whom 70% reported greater-than-minimal depressive symptoms, 60% greater-than-minimal anxiety symptoms, and 92% moderate or high perceived stress. Following a single interaction with EVA, depression knowledge increased significantly, from a mean ADKQ score of 6.88 (SD=1.85) to 8.12 (SD=2.20), t(49) = -5.03, p<.001, representing a large effect size (d=1.74). The chatbot was rated highly for acceptability, appropriateness, and feasibility, and participants reported strong intentions to use and recommend it, as well as high satisfaction with its educational content, usability, and self-help resources. Conclusions: A brief interaction with a mental health chatbot developed with and for ALWH in Peru significantly increased depression knowledge and was rated highly acceptable and feasible. Mental health chatbots may offer a low-cost, scalable approach to support mental health education and linkage to care within adolescent HIV services. Future longitudinal studies should assess sustained impact on mental health outcomes and help-seeking behavior; however, the benefits of chatbots should be weighed against their potential mental health risks.

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.