JAIDS Journal of Acquired Immune Deficiency Syndromes

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

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.

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.

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

Background. 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.

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 [≥] 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 [≥] 1.30; p [≤] 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.

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 [≥]16 years with [≥]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 [≥]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.

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.

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.

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.

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.

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

Background As HIV incidence declines in African settings with high treatment coverage, it remains unclear how transmission is structured within populations and whether new infections arise from external introductions or local transmission. We characterized the molecular epidemiology of ongoing transmission in a mature multi-subtype epidemic in Uganda. Methods We analyzed HIV genome sequences and survey data from the Rakai Community Cohort Study collected between 1994 and 2019. We identified phylogenetic clusters at 5.3% and 2.5% genetic distance thresholds and inferred long-horizon transmission chains with phylogeographic models. Newly diagnosed infections identified between 2016 and 2019 were mapped onto subtype-specific phylogenies to assess their origins and transmission context. A Bayesian negative binomial branching process model estimated undersampled chain sizes and case reproduction numbers. Findings Among 4,215 participants living with HIV between December 2016 and May 2019, 474 were newly diagnosed, of whom 269 had at least one pure-subtype sequence available. We identified 649 phylogenetic clusters at 5.3% genetic distance and 673 phylogeographic chains including [&ge;]2 individuals. Most clusters and chains were small (median sizes 2 [IQR 2-3] and 3 [2-4], respectively), with new diagnoses rarely clustered together. Only 46/269 (17.1%) new diagnoses had phylogeographic external origins, while the remaining 82.9% were partially or fully linked to local chains. Mixed-subtypes/recombinant chains were larger and had higher case reproduction numbers (A1/D: 0.84 [95% CrI: 0.79-0.93]; mixed: 0.84 [0.73-0.97]) than single-subtype chains (A1: 0.56 [0.51-0.60]; D: 0.63 [0.59-0.66]; C: 0.55 [0.41-0.71]), yet all estimates were less than one. Interpretation HIV transmission was fragmented across numerous, slowly propagating lineages, maintained by local clusters with occasional introduction. Continued transmission across many chains suggests that further reductions in HIV incidence will require maintaining high levels of population-wide treatment and prevention coverage. Funding The National Institute of Allergy and Infectious Diseases, the Gates Foundation, and the HIV Prevention Trials Network Laboratory Center