AIDS and Behavior

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: 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.

Adolescents with perinatally acquired HIV carry a high burden of depression and anxiety, and where specialist mental health services are scarce, peer-led physical activity has been proposed as a low-cost supportive intervention. Whether such programs reach girls and boys equally, and whether gendered constraints shape who is able to take part, has received little attention. Treating HIV status, gender, and adolescence as intersecting rather than additive axes of disadvantage, we examined participation in the Positive Running Program, a peer-led structured physical activity intervention delivered around antiretroviral therapy centers in Karnataka and Tamil Nadu, southern India. We conducted a cross-sectional convergent mixed-methods study among 150 adolescents and young people with perinatally acquired HIV (100 boys and young men, 50 girls and young women; median age 17 years, interquartile range 15-19; 91% virally suppressed). Depressive and anxiety symptoms were screened using the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder-7 scale, a score of 5 or above on either instrument was classified as a common mental disorder. High program adherence was defined as attendance at 65% or more of scheduled sessions. Associations were estimated using logistic regression adjusted for age, with gender-stratified models and an adherence-by-gender interaction term. Four focus group discussions with 28 participants and peer facilitators were analyzed using reflexive thematic analysis, with themes generated inductively and interpreted through an intersectional lens and through self-determination theory. Quantitative and qualitative findings were integrated at the interpretive stage. Girls and young women attended fewer sessions than boys and young men (mean 61.6% versus 65.6%; p=0.025) and were less likely to reach the pre-specified [&ge;]65% adherence threshold (10/50, 20% versus 57/100, 57%; p<0.001). They also had a higher prevalence of a positive depression screen (33/50, 66% versus 43/100, 43%; p=0.009) and of any common mental disorder (36/50, 72% versus 52/100, 52%; p=0.022). Higher adherence was associated with lower odds of a common mental disorder overall (adjusted odds ratio 0.31, 95% CI 0.13-0.68) and among boys and young men (0.33, 0.14-0.75); among girls and young women, only 10 participants met the adherence threshold and the estimates were imprecise. Qualitative findings located the constraints upstream of the program, in household authority over girls' time, restrictions on mobility outside the home, care-giving obligations, and community disapproval of girls exercising in public. The central finding concerns participation rather than benefit: girls and young women were half as numerous among participants and attended less consistently, clustering just below the high-adherence threshold. This differential opportunity to participate arises where gendered household authority intersects with the constrained autonomy of adolescence and the concealment demanded by HIV status. Interpreted through self-determination theory, the program supported competence and relatedness for those who attended but did little to secure the autonomy girls needed to attend consistently. The cross-sectional design precludes causal inference, including about the direction of the association between attendance and symptoms. Peer-led physical activity programs in this setting should treat gender inequality not as background context but as a determinant of participation and a core target of design.

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.

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: 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.

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.

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.

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.

Demand for preventative health care is weak in low-income settings. In a field experiment in a low-income, high-risk setting, we evaluated whether demand for a new bio-medical preventative health product, offered free at public health clinics, responds to digital feedback-based intensive information on health risks and benefits of prevention along with a clinic referral enabling access to the product. In our sample of women aged 18-24 years, we find a large correction in risk beliefs sustained six months after the intervention. Against a background of very low baseline usage, within six months we find a 5.8 percentage point increase in take up of the prevention method, a level of uptake which is very large relative to the control group. Reassuringly, there is no meaningful difference in up-take amongst baseline high- risk and low-risk individuals.

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.

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.

Background: Adolescence is a critical period for HIV prevention, yet many adolescent girls and young women (AGYW) experience this developmental transition within contexts of poverty, gender inequality, and limited social protection. As HIV pre-exposure prophylaxis (PrEP) expands across eastern and southern Africa, little attention has been paid to the ethical implications of providing PrEP within these social contexts. Methods: We conducted a qualitative study in two rural districts of Lesotho using focus group discussions with AGYW aged 16-24 years and group interviews and individual interviews with village health workers and village chiefs. Data were analysed using reflexive thematic analysis. Results: Three interconnected themes described how social vulnerability shaped young women's sexual and reproductive health (SRH) and opportunities to benefit from PrEP. First, adolescence was characterised by limited SRH support, age-disparate and transactional relationships, and multiple forms of sexual violence occurring across homes, schools, hostels, and communities. Second, early and unintended pregnancy and child marriage accelerated transitions into adult roles and responsibilities before many young women were developmentally and socially prepared. Third, families, schools, communities, and existing protection systems frequently failed to provide adequate support, leaving young women to navigate violence, pregnancy, and early marriage with limited protection or recourse. Conclusions: Providing PrEP to AGYW in contexts where social protections remain limited raises important ethical considerations. Expanding access to biomedical HIV prevention is necessary but insufficient. Ethical PrEP provision requires implementing social protection alongside biomedical prevention so that young women are supported not only to access PrEP, but also to meaningfully benefit from it.

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.

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.

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.

Adolescent girls and young women in Zambia face barriers to accessing HIV and sexual and reproductive health services. We conducted a cross-sectional survey among 846 female students at a university in Zambia to assess acceptability of receiving these services in hair salons and explore whether HIV acquisition risk influenced acceptability of HIV services. Acceptability varied by service, ranging from 25% to 50%. Higher HIV acquisition risk may increase the acceptability for HIV services. Hair salons may be a promising community-based, demedicalized setting for delivering selected HIV and sexual and reproductive health services to HIV at-risk female students.

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.

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.