JAIDS Journal of Acquired Immune Deficiency Syndromes

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.

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.

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

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.

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

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.

Purpose Kaposi sarcoma (KS) remains one of the most common HIV-associated malignancies in sub-Saharan Africa (SSA). While loss to follow-up (LTFU) has been well documented among KS patients managed within HIV primary care, little is known about retention after patients transition into specialized oncology care, where treatment pathways, toxicities, costs, and follow-up schedules differ substantially. Because LTFU is unlikely to occur at random, patients who disengage from care may differ systematically from those retained with respect to disease severity, treatment response, and mortality risk, potentially biasing survival estimates and underestimating cancer-related mortality. This study aimed to estimate the cumulative incidence of LTFU among patients with KS receiving care at Tanzanias national cancer referral center, accounting for death as a competing event, and to identify factors associated with LTFU. Methods This retrospective cohort study included 251 patients with KS treated at Ocean Road Cancer Institute (ORCI) between January 2021 and December 2023. The primary outcome was LTFU, with death treated as a competing event. Cumulative incidence of LTFU at 6, 12, 18, and 24 months was estimated using the cumulative incidence function. Predictors of LTFU were assessed using univariable and multivariable Fine-Gray subdistribution hazards regression. Results Among 251 patients, 214 (85.3%) had epidemic (HIV-associated) KS and 37 (14.7%) had endemic (non-HIV-associated) KS. Males accounted for 62.2%. Accounting for death as a competing event, the cumulative incidence of LTFU was 27.6% (95% CI, 22.0-33.1) at 6 months, 36.4% (95% CI, 30.5-42.4) at 12 months, 43.3% (95% CI, 37.2-49.4) at 18 months, and 46.6% (95% CI, 40.4-52.7) at 24 months. In multivariable Fine-Gray regression, absence of oral involvement (adjusted subdistribution hazard ratio [aSHR], 0.37), reachable telephone contact (aSHR, 0.54), and initial chemotherapy rather than radiotherapy (aSHR, 0.44) were independently associated with lower risk of LTFU. Conclusion Nearly half of patients with KS were LTFU within two years, substantially limiting reliable assessment of cancer outcomes in this setting. Strengthening retention strategies, including maintaining reliable patient contact information and implementing routine phone-based follow-up, may offer feasible, scalable approaches to improve continuity of care, enhance survival monitoring, and strengthen cancer surveillance in resource-limited 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: Vaccination of people with HIV (PWH) on suppressive antiretroviral therapy (ART) represents a novel approach for evaluating candidate broadly neutralizing antibody (bnAb) immunogens for preventive and therapeutic HIV vaccines. Given pre-existing immunity in PWH, the safety of this approach requires careful assessment prior to broader application. Here, we report on the design and safety of the RENEW-SHCS study which evaluates the immunization of PWH with BG505 SOSIP.v4.1-GT1.1, an immunogen engineered to induce precursors of CD4 binding site (CD4bs)- and V2-apex targeting bnAbs. Methods. RENEW-SHCS is a phase I, open-label, non-randomized vaccination trial evaluating a single dose of the recombinant germline-targeting envelope trimer BG505 SOSIP.v4.1-GT1.1 (GT1.1), adjuvanted with 3M052-AF and Aluminum hydroxide (alum), in PWH on suppressive ART enrolled from the Swiss HIV Cohort Study. Participants were previously classified as bnAb or non-neutralizing antibody (nnAb) inducers, with a target enrollment of 15 per group, and were monitored for safety and immunogenicity for 24 weeks while continuing standard ART. Due to an out-of-specification stability measurement of adjuvant 3M052-AF the trial was paused after 23 immunizations and subjected to an unscheduled interim safety and reactogenicity assessment comprising protocol defined outcome measures (adverse events, clinical laboratory measurements and HIV-1 viral load). Results. Twenty-three participants (10 bnAb and 13 nnAb inducers, median age 59 years, 17 male / 6 female) were vaccinated between March and August 2025 before interruption of the trial. All participants completed follow-up with full protocol adherence. The interim-safety analysis confirmed that no vaccine-related serious adverse events occurred. Solicited local (96%) and systemic (83%) reactions were common, predominantly grade 1-2, transient, and self-limited. Transient laboratory changes occurred but mostly remained within the normal range, with no vaccine-related grade 3 abnormalities. We observed predominantly transient local and systemic reactions, which were similar or milder to the reactogenicity profile reported for immunization of adult people without HIV (PWOH) with GT1.1 adjuvanted with AS01b reported in the IAVI C101 trial. No viral rebound under ART occurred. One participant experienced two viral blips (>50 HIV-1 RNA copies/ml), one before and one 16 weeks after vaccination with subsequent re-suppression. All others maintained viral suppression (<50 copies/ml) throughout follow-up. Conclusion. RENEW-SHCS demonstrated a favorable safety and reactogenicity profile of single dose immunization with GT1.1 in PWH, comparable to that observed in PWOH. The findings of this phase I study support the feasibility of vaccinating ART-treated PWH in trials of preventive and therapeutic HIV vaccine strategies.

Background: Doxycycline post-exposure prophylaxis (doxy-PEP) reduces the incidence of bacterial sexually transmitted infections (STIs) among men who have sex with men and transgender women (MSMTW), but it may select for antimicrobial resistance (AMR). AMR development will depend in part how doxy-PEP changes rates of antibiotic use. Methods: We conducted a retrospective electronic medical record review of antibiotic prescriptions received by patients at the Massachusetts General Hospital Sexual Health Clinic from January 1, 2023, to December 27, 2025. Using a Bayesian negative binomial regression, we assessed the direct, indirect, and combined effects of doxy-PEP implementation on antibiotic prescription rates among doxy-PEP-eligible MSMTW who were receiving HIV pre-exposure prophylaxis. Results: Controlling for direct effects, the cohort's total antibiotic prescription rate decreased by 10% (0.90, 95% CI 0.87 - 0.94) for every 100 doxy-PEP starts. Doxy-PEP users were prescribed antibiotics at double the rate predicted in the absence of doxy-PEP implementation, and, controlling for indirect effects, received 3.40 (95% CI 2.95 - 3.91) times the antibiotic prescriptions of patients not using doxy-PEP. Doxy-PEP non-users were prescribed antibiotics at less than half the rate predicted in the absence of doxy-PEP. The full cohort's overall antibiotic prescription rate increased by 1.4 times after doxy-PEP implementation. Conclusions: Individuals who are taking doxy-PEP have higher antibiotic prescription rates, increasing selection for antibiotic-resistant bacteria in these individuals. However, doxy-PEP-driven decreases in the overall incidence of bacterial STIs have the potential to decrease selective pressure for resistant organisms in those not using doxy-PEP.

Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection is associated with accelerated liver disease, but whether coinfection is associated with newly documented social determinants of health (SDoH) is unclear. We conducted a retrospective cohort study using TriNetX across 110 U.S. healthcare organizations (2010-2026). We propensity score matched adults with HIV/HBV to adults with HIV or HBV monoinfection. We organized newly documented SDoH indicators using a dynamic individual-level framework with four clinically recognized domains of social disadvantage: material vulnerability, healthcare access and engagement, interpersonal adversity, and psychosocial vulnerability. Matched cohorts included 10,071 HIV/HBV-HIV pairs and 9,659 HIV/HBV-HBV pairs (mean age, 47 years; 79% male; 66% non-White; median follow-up, 3.3 years). Over 178,900 person-years, HIV/HBV was associated with higher risk of the primary SDoH composite compared with HIV (11.5% vs 9.7%; incidence rate, 2.50 vs 1.97 per 100 person-years; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.15-1.37) and HBV (11.0% vs 6.4%; incidence rate, 2.39 vs 1.67; HR, 1.50; 95% CI, 1.35-1.67). HIV/HBV was also associated with higher material vulnerability and healthcare access and engagement composites in both comparisons, including housing instability, food insecurity, financial insecurity, insurance instability, and care disengagement/nonadherence (HR range, 1.22-3.33 vs HIV; 1.31-1.94 vs HBV). In the HBV comparison, HIV/HBV was additionally associated with interpersonal adversity, primary support stressors, and violence or victimization (HR range, 1.36-2.16). Findings were robust across sensitivity analyses. HIV/HBV was associated with more newly documented SDoH than monoinfection, supporting dynamic SDoH assessment.

Abstract Background: Cervical cancer is the most common malignancy among Zambian women, and HIV coinfection accelerates disease progression. However, in the contemporary era of widespread antiretroviral therapy, the determinants of cervical cancer disease state among women living with HIV at Zambia's primary oncology referral centre are not fully understood. This study aimed to investigate these determinants at the Cancer Disease Hospital in Lusaka. Methods: An analytical cross-sectional study was conducted using medical records of 198 WLHIV with histologically confirmed invasive cervical cancer. Data on demographics, HIV status (CD4 count, viral load), and cancer characteristics (FIGO stage) were abstracted. Descriptive statistics, bivariate analyses, and multivariable logistic regression were performed. Results: The prevalence of advanced stage (Stage III/IV) cervical cancer was 34.4% (68/198), while 54.5% presented with Stage IIB disease. Metastatic disease was only 7.1% (14/198). The peak age of diagnosis was 40-49 years (51.5%). Median CD4 count was 484 cells/uL, and 89.4% had suppressed viral loads. No significant association was found between HIV disease status and advanced-stage cancer (CD4 <200: AOR 1.42, 95% CI 0.68-2.96; detectable viral load: AOR 1.38, 95% CI 0.71-2.68). Younger WLHIV aged 30 to 39 years had the highest proportion of advanced-stage disease (38.5%), as did peri-urban residents (40.0%) compared to Lusaka residents (30.0%). Conclusion: In the ART era, HIV disease status is no longer the dominant determinant of cervical cancer stage among WLHIV at CDH who develop invasive cancer, likely due to effective immune reconstitution. However, persistent Stage IIB presentation indicates inadequate screening coverage. Younger WLHIV and peri-urban residents are at highest risk of late-stage diagnosis. Keywords: Cervical Cancer; Uterine Cervical Neoplasms; Antiretroviral Therapy; HIV infections; FIGO Staging; Zambia