JAIDS Journal of Acquired Immune Deficiency Syndromes

Population size estimates (PSE) for gay, bisexual, and other cisgender men who have sex with men (GBMSM) remain difficult where stigma and criminalization limit data collection and HIV resource allocation. We aim to assess whether Google Trends and a gay social networking app can provide standardized, low-cost population size estimates (PSE) for gay, bisexual, and other cisgender men who have sex with men (GBMSM) in Senegal, Ghana, Mozambique, and Indonesia. We analyzed country-level and local GT relative search volumes for "porn" and "gay porn" from September 2024 to September 2025. Pornhub global review data were applied to produce proportional GBMSM PSEs. App estimates were derived from monthly active users and extrapolated to annual users. Proportional estimates were multiplied by the male population aged 15-49 years to obtain absolute PSE and compared with UNAIDS Key Population Atlas estimates. Sensitivity analyses used survey-based multipliers and alternative search-term combinations. GTPSE ranged from 0.37% in Mozambique to 1.92% in Indonesia, while app-based estimates ranged from 0.29% in Mozambique to 1.34% in Ghana. GTPSE exceeded UNAIDS estimates in Ghana, Mozambique, and Indonesia. App-based estimates exceeded UNAIDS estimates in Ghana and Mozambique. Maputos estimated GBMSM proportion was substantially higher than Mozambiques national estimate. GTPSE generally exceeded UNAIDS estimates, which may reflect underestimation in stigmatizing settings where GBMSM are less likely to be reached through field-based methods or mainstream health services. Social network app estimates were lower in some countries, highlighting variability in platform access and geographic differences in the concentration of social networks. Internet-derived data may offer a low-cost, feasible approach to GBMSM PSE in low- and middle-income settings. Further validation through digital data linkages could strengthen HIV prevention and treatment planning.

Men continue to test for HIV less often than women in many settings, including Kenya. Community-based HIV testing may reduce access barriers, but evidence on factors associated with mens use of community-post services remains limited. This analytical cross-sectional mixed-methods study examined socio-demographic and behavioral factors associated with use of community posts for HIV testing among adult men in Kericho County, Kenya. Quantitative data were collected using self-administered questionnaires at two community posts and two facility-based Comprehensive Care Centres. The Kobo export contained 438 questionnaire records; 41 pretest records were excluded in line with the study protocol, leaving 397 records for analysis. Community-post use in the preceding year was reported by 208 of 396 respondents with complete outcome data (52.5%). In adjusted analysis, community-post use was higher among employed men (AOR 2.94, 95% CI 1.48-5.82; p=0.002) and men engaged in business (AOR 2.56, 95% CI 1.15-5.69; p=0.021) than among unemployed/other men. Age, marital status, religion, education and monthly income were not independently associated with community-post use. In the behavioral model, respondents who were unwilling or unsure about participating in future community HIV-testing campaigns had lower odds of community-post use (AOR 0.20, 95% CI 0.10-0.39; p<0.001). Frequent travel or migration (AOR 0.19, 95% CI 0.06-0.65; p=0.008) and unprotected sex (AOR 0.54, 95% CI 0.34-0.87; p=0.012) were also associated with lower odds of community-post use after adjustment. These findings identify occupational and selected behavioral factors associated with community-post use among the men studied; the cross-sectional design does not establish causality.

Introduction: HIV care and treatment programs around the world continue to evolve in response to changes in clinical guidelines, evidence-based practices, domestic and donor funding for the HIV response, new technological developments, and changing weather patterns. Since 2009, the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium has conducted periodic surveys to document the characteristics of participating clinics and the availability of HIV-related services across diverse settings -- information that provides important context for understanding variations and trends in HIV care outcomes. This paper describes the protocol for IeDEA's 2026 site assessment survey, launched in August 2026. Methods and analysis: This cross-sectional descriptive study aims to document HIV-related services and practices among clinics in 42 countries. The survey explores the characteristics and services provided at HIV care and treatment sites participating in IeDEA in 2026, along with real-world adoption and implementation of evidence-based service delivery strategies for people living with or at risk of HIV. Designed for self-administration, the survey questionnaire was developed through two complementary processes: a review of questions and data collected through IeDEA' prior consortium-wide surveys and an open call to IeDEA investigators for new survey content to advance a timely implementation science agenda relevant to the global HIV community. Survey materials and links to an online REDCap questionnaire will be distributed to 232 eligible clinics across IeDEA in September 2026, with a deadline of November 30, 2026, for completion. Planned analyses will examine the following topics: HIV care amidst funding constraints; the roll-out of differentiated service delivery models; pre-exposure HIV prophylaxis; long-acting injectable antiretroviral therapy (ART); prevention, screening and/or treatment services for viral hepatitis, mental health and substance use disorders, cardiovascular disease, and cancers among PLHIV; the integration of HIV care with other health services; and clinic vulnerability to extreme weather events. Ethics and dissemination: A "non-human subjects" research designation was determined by the Vanderbilt University Medical Center Human Research Protections Program. Survey findings will be shared with local partners and stakeholders across IeDEA, disseminated at regional and global conferences, and published in peer-reviewed journals.

Introduction: Japan achieves high retention and viral suppression among people on antiretroviral therapy, yet treatment starts late. Most people obtain subsidised treatment through a physical disability certificate for HIV-related immune dysfunction, which requires two blood tests at least four weeks apart. We quantified the diagnosis-to-treatment cascade, identified who waits and tested whether the second test changes certification. Methods: Retrospective cohort of people newly diagnosed with HIV at 11 designated AIDS core hospitals in 2015 to 2024. We measured intervals from screening to hospital visit and to antiretroviral therapy, and emulated certification from the first test alone and from the two-test rule under every possible number of non-laboratory criteria (k = 0 to 8). Results: Of 1302 people (96% men; 68% with CD4 <350 cells/L or AIDS), 1036 (80%) followed the two-test pathway and 261 started treatment after one test, mostly because of AIDS or acute infection. People reached the hospital a median of 11 days after screening. Treatment then began a median of 70 days after the first visit in the two-test pathway and 11 days in the single-test pathway; 0.2% and 60.9% started within 14 days. Delay rose with CD4 count: 46 days when the mean count was [&le;]200 cells/L, 117 days when it was >500 with a laboratory criterion (16% of the two-test pathway) and 334 days when it was >500 without one (3%; adjusted hazard ratio 0.14, 95% confidence interval 0.09 to 0.23). Medians ranged from 35 to 96 days across facilities. The second test changed little: the first CD4 count agreed with the mean of two (intraclass correlation coefficient 0.959), HIV-RNA [&ge;]5000 copies/mL persisted in 97.6%, and certification status agreed in 99.0% for k [&ge;]1 (92.5% for k = 0), with discordance concentrated near 500 cells/L; the first test gave a milder grade in at most 2.9%. Conclusions: The statutory second test adds at least four weeks before antiretroviral therapy in Japan without changing who is certified, and delays most the people with the highest CD4 counts. Certification on a single test, with treatment separated from the subsidy procedure, would remove a delay that has no clinical or administrative justification.

Precision targeting is essential for maximising impact and cost-effectiveness of interventions at this stage of the HIV response in Malawi. We aimed to measure gaps in access to and use of condoms, HIV testing, pre-exposure prophylaxis (PrEP) and voluntary medical male circumcision among HIV-negative individuals at public health facilities and social venues (bars, rest houses and liquor stores) in Blantyre, Malawi. We analysed cross-sectional data from 2,227 HIV-negative patients at government clinics and 1,634 patrons at social venues recruited in the Clinic vs Venue (CLOVE) study between January and March 2022. We estimated gaps in access to and use of condoms, HIV testing, PrEP and circumcision. Estimates were stratified by risk group, defined as reporting transactional sex, having multiple sex partners in the past 4 weeks, being female aged 15 to 24, or being male aged 30 and above. Access and use were based on self-reports. Overall, 30% of clinic and 60% of venue participants reported higher risk. Among men, we found a gap between access to condoms and condom use at last sex (76.7% vs 29.8% among clinic men; 75.4% vs 36.7% among venue men). Among women, the gap between access and use of condoms was 65.9% vs 18.0% at clinics and 79.9% vs 46.0% in the venues. Approximately 80-85% of participants reported knowing where to get an HIV test in Blantyre but less than half reported testing in the past 6 months. Use of PrEP was low (~2%). Comparable proportions of men who paid for sex and those with multiple partners (~77%) reported being circumcised, but this was lower among those aged 30 years or older (~57%). Despite expanded HIV prevention services in Blantyre, gaps remain in the uptake of prevention services among people reachable at public health facilities and social venues. Use of PrEP was particularly low across all groups. Condom and testing use remained suboptimal despite high reported access. Targeted efforts are needed to address barriers to uptake, particularly for PrEP among high-risk venue-based populations.

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.

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.

Long-acting injectable human immunodeficiency virus (HIV) medicines expand treatment and prevention choices, but willingness to use them does not establish readiness to begin. We examined readiness to start these options, associated factors and conditions for acceptance among people living with HIV and pre-exposure prophylaxis (PrEP)-service clients in Uganda. This cross-sectional study analysed 225 participants at Mildmay Hospital and Kajjansi Health Centre IV in central Uganda. Readiness meant preferring initiation immediately or within three months. Modified Poisson regression estimated adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs), including age-by-service-group interaction. Separate models examined informational, perceptual and financial factors, adjusting for service group, age and sex. Logistic marginal standardisation checked demographic and expanded age comparisons. Overall, 108 participants (48.0%) were ready to start injectable HIV treatment or prevention, 111 (49.3%) wanted more information about these options, and six (2.7%) preferred initiation in six to twelve months. Readiness was 80.8% among people living with HIV aged 15-24 years and 34.4% among those aged 25 years or older (aPR 2.35, 95% CI 1.63-3.38). Corresponding proportions among PrEP-service clients were 39.2% and 41.4% (aPR 0.95, 95% CI 0.60-1.50; interaction p=0.002). In separate adjusted models, clinic-staff information (aPR 1.94, 95% CI 1.42-2.66), belief in greater effectiveness (2.00, 1.43-2.80) and a one-point increase in benefit score (3.27, 2.36-4.55) were associated with higher readiness. A one-point increase in concern score (0.70, 0.60-0.80) and financial difficulty sometimes or more often (0.68, 0.48-0.96) were associated with lower readiness. Fewer side effects was the leading condition for accepting injectable HIV treatment or prevention across service and readiness groups. Nearly half of participants were ready to start, while a similar proportion wanted further information about injectable options. Programmes should assess intended initiation timing alongside willingness and address safety, appointment flexibility, privacy and affordability through counselling and service planning.

Retention in antiretroviral therapy (ART) programmes remains a major public health challenge in HIV care, with loss to follow-up (LTFU) and death threatening treatment success. Because these outcomes are competing events, conventional survival methods may yield biased estimates of their incidence and associated risk factors. To estimate the cumulative incidence of LTFU and mortality and identify factors associated with these outcomes among adults receiving ART in Northern Ghana using a competing-risks framework. We conducted a retrospective cohort study of 329 adults living with HIV who initiated ART at Nalerigu Baptist Medical Centre, Ghana, between January 2013 and December 2019. Fine--Gray subdistribution hazard models were used to evaluate predictors of LTFU and death while accounting for competing risks. Cause-specific Cox proportional hazards models were fitted as a sensitivity analysis. The incidence rates were 2.2 per 100 person-months (95% CI: 1.9--2.6) for LTFU and 0.74 per 100 person-months (95% CI: 0.57--0.98) for death. At 36 months, the cumulative incidence was 50.2% for LTFU and 16.0% for death. Patients residing closer to the clinic had a lower cumulative incidence of LTFU than those living farther away (SHR = 0.68, 95% CI: 0.49--0.93), whereas higher baseline weight was associated with increased LTFU (SHR = 1.02 per kg, 95% CI: 1.00--1.04). Mortality was lower among patients receiving efavirenz-based regimens (SHR = 0.27, 95% CI: 0.15--0.50), females (SHR = 0.39, 95% CI: 0.18--0.85), and those with higher baseline weight (SHR = 0.93 per kg, 95% CI: 0.90--0.96). Findings were broadly consistent in cause-specific Cox models. LTFU was substantially more frequent than mortality among adults receiving ART in Northern Ghana. Travel distance to the treatment facility was an important barrier to retention, while ART regimen, sex, and baseline weight were associated with mortality. Expanding access to ART services through decentralized and community-based models may improve retention and support efforts to achieve HIV control targets.

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.

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.

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.

Cash incentives are widely used in clinical research to support recruitment and retention, yet their ethical implications, particularly in high-risk settings such as HIV cure-related studies, remain inadequately understood. This study examined how key stakeholders perceive participant payment relative to other study characteristics when deciding whether to participate in HIV cure research. Using a choice-based conjoint (CBC) experiment, we assessed preferences among people living with HIV (PLWH), HIV researchers, and Institutional Review Board (IRB) members/bioethicists. Participants (N=88) completed eight choice tasks involving hypothetical HIV cure study scenarios varying across six attributes: incentive amount, invasiveness, requirement to pause HIV medications, time commitment, first-in-human status, and cost reimbursement. Across all participants, payment amount emerged as the most influential attribute (29.3%), followed by procedure invasiveness (22.3%) and the requirement to pause HIV medication (17.6%). The highest hypothetical payment level ($200 per visit) was significantly preferred. However, subgroup analyses revealed important differences: PLWH prioritized payment most strongly, whereas researchers and IRB members/bioethicists placed greater emphasis on minimizing invasiveness. The requirement to pause HIV medication was a salient concern across groups, though relatively more influential for IRB members/bioethicists than for PLWH. Time commitment and ancillary cost reimbursement had comparatively lower impact on decision-making. These findings highlight the central role of financial incentives in shaping willingness to participate in HIV cure research, raising ethical considerations regarding potential undue influence, especially in higher-risk studies. At the same time, stakeholders value minimizing procedural risks and disruptions to treatment. This study underscores the need for clearer guidance on appropriate payment practices and for balancing incentives with ethical safeguards, particularly in trials involving antiretroviral therapy interruption.

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 Men who have sex with men (MSM) in the Jakarta Metropolitan Area (JMA), Indonesia are disproportionately affected by HIV. Pre-exposure prophylaxis (PrEP) is a viable strategy for addressing enduring HIV disparities, yet remains underutilized among MSM in the JMA. Patterns and influences of PrEP use may inform future intervention targets but have not been extensively studied in this context. Methods Guided by the Andersen's Behavioral Model for Health Services Use, the present study investigated multidimensional correlates of varied PrEP use patterns among 183 JMA-based MSM aged 18-51 (median age=29) and at elevated risk of HIV infection. The multinomial regression model identified factors associated with current PrEP use and some use in the past, compared with never use (reference category). Results In the present study, 107 (58%) participants reported never use, 34 (19%) current use, and 42 (23%) some use of PrEP. Current PrEP use was negatively associated with HIV stigma and positively with perceived social support, online HIV information seeking, and sexualized drug use. Some PrEP use was negatively associated with HIV stigma and positively with online HIV information seeking. Conclusions The study findings provide support for the Andersen model's emphasis on predisposing characteristics, enabling resources, and need factors when tailoring PrEP implementation for higher-risk MSM in the JMA. Addressing stigma, reinforcing social support and HIV knowledge, and integrating PrEP care within multiple health care systems appear viable avenues for improving PrEP adoption in this key population.

Background: Global HIV programmes are transitioning virally suppressed children and adolescents with HIV (CAWH) from prior regimens to dolutegravir-based antiretroviral therapy (ART). However, the supporting evidence largely stems from randomised trials in viraemic CAWH. The effect of transition for virally suppressed CAWH is unknown. Methods: We used observational, de-identified data from 724 clinics in KwaZulu-Natal, South Africa. We sequentially emulated three distinct target trials to estimate the effect of transitioning to dolutegravir-based ART in three paediatric populations: i) ages 8-17 years taking efavirenz-based ART, ii) 8-17 years taking ritonavir-boosted lopinavir (LPV/r)-based ART, and iii) 0-7 years taking LPV/r-based ART, all with a last viral load <1,000 copies/mL. The risk difference (RD) of death or viraemia >1,000 copies/mL through 12 and 24 months was estimated using an inverse probability weighting approach. Findings: From January 2020 to August 2024, 37,145 CAWH contributed 454,081 person-trials. In CAWH initially taking efavirenz, the standardised 12-month risk of death or viraemia was 11.9% with continued efavirenz and 6.7% with transition to dolutegravir (RD -5.2 [95% CI -5.8 to -4.6]). In older CAWH initially taking LPV/r, these risks were 17.8% and 9.5%, respectively (RD -8.3 [-10.0 to -6.8]). In younger children, the respective risks were 15.8% and 6.7% (RD -9.0% [-12.7 to -5.4]). Where available, 24-month endpoints showed slightly greater RDs. Interpretation: This large-scale, causal analysis highlights improvements in viral suppression and strongly supports ongoing transition to dolutegravir-based ART for virally suppressed CAWH. Funding: Gates Foundation, National Institute for Health and Care Research, Swiss National Science Foundation

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.

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.