AIDS

Background. In the era of successful antiretroviral therapy (ART), mood disturbance remains highly prevalent in people with HIV (PWH). In the present study, we investigated the long-term legacy effects of long delay in ART initiation and low nadir CD4 count on mood symptoms in adults with HIV. The impacts of demographic and other HIV clinical factors were also examined. Methods. A total of 109 PWH (disease duration: 24.6{+/-}9.3 years) and 42 demographically matched healthy participants (people without HIV, or PWoH) participated in a cross-sectional study (41-70 years old (55.6{+/-}6.8), 62.9% African Americans, 27.2% female, 14.3{+/-}2.9 years of education). Mood symptoms were assessed with the Beck Depression Inventory-II (BDI-II) and the Profile of Mood States (POMS). A comprehensive neuropsychological test battery was administered to assess neurocognitive function. Results. Despite largely comparable neurocognitive performance between PWH and PWoH , PWH had worse mood symptoms than PWoH, including higher total BDI-II (p<.001) and total POMS scores (p=.002), as well as higher score in all POMS sub-scores (p<.007), except Vigor (p=.724). Within the PWH group, longer delays in ART initiation, lower nadir CD4 count, and lower educational attainment were associated with worse mood symptoms. By contrast, current plasma CD4+ cell count, plasma detectable viral load, and HIV disease duration were not associated with either BDI-II or POMS score. Conclusion. Mood disturbance is highly prevalent in PWH on ART. The long-term legacy effects of delay in ART initiation and low nadir CD4 count on mood management reinforce the necessity of early ART initiation in clinical practice.

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.

Background Viral load suppression (VLS) remains suboptimal among adolescents and youth living with HIV (AYLWH) in Malawi. Depressive symptoms may affect treatment adherence and HIV outcomes, but evidence is limited. We assessed the association between depressive symptoms and VLS among AYLWH using Malawi Population-based HIV Impact Assessment (MPHIA) 2020-2021 data. Methods We conducted a cross-sectional secondary analysis of AYLWH aged 15-24 years. VLS was defined as HIV RNA less than 200 copies/mL and depressive symptoms as a Patient Health Questionnaire-2 score of 3 or higher. Survey-weighted logistic regression assessed associations with VLS, adjusting for sex, education, residence, household wealth, alcohol use, Teen Club participation, and awareness of HIV-positive status. Findings Among 201 participants, viral-load results were available for 200; 137 (68.5%) achieved VLS. Six (3.0%) participants had depressive symptoms. Depressive symptoms were not associated with VLS in univariable analysis (OR 0.8, 95% CI 0.1-4.6; p=0.80) or multivariable analysis (aOR 0.3, 95% CI 0.1-2.4; p=0.28). Urban residence (aOR 0.2, 95% CI 0.1-0.5; p=0.0020) and unawareness of HIV-positive status (aOR 0.1, 95% CI 0.02-0.1; p<0.001) were associated with lower odds of VLS. Interpretation Depressive symptoms were not significantly associated with VLS, although their low prevalence and PHQ-2 limitations reduced precision. The findings highlight the importance of strengthening HIV-status awareness and addressing context-specific barriers to care among AYLWH. Funding This secondary analysis received no specific funding.

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 and stroke are major contributors to disability in sub-Saharan Africa, yet their combined impact on cognitive and motor functioning remains poorly understood. Botswana has a high prevalence of HIV and rising stroke incidence, underscoring the need to characterize impairment to inform neurorehabilitation. Objective: To examine differences in cognitive performance, motor function, and activities of daily living between adults living with HIV only and those living with both HIV and stroke in Botswana. Methods: Thirty-three adults (19 HIV only; 14 HIV/ stroke) completed standardized cognitive (e.g. MoCA and Digit Symbol Coding [DSC]), and motor assessments (such as Box and Block Test [BBT], Grooved Pegboard [GPB], Grip Strength [GS], 10-Meter Walk Test [10MWT], Timed Up and Go [TUG]), and ADL measures (such as Barthel Index, Lawton IADL). Group comparisons used Wilcoxon rank-sum tests. Impairment was determined using both international z-score norms and Botswana-specific cutoffs from a prior cohort study. Results: Cognitive impairment was evident in both groups, but DSC z-scores were worse in the HIV/stroke vs HIV only group (median= -2.71 vs -1.34, p=0.015). Gross motor function showed deficits in the HIV/stroke group, including lower dominant-hand BBT performance (median z-score -2.79 vs. -1.75; p=0.008). Fine motor dexterity was markedly reduced in the HIV/stroke group, with GPB dominant-hand median z-scores of -4.26 vs. -1.40 (p=0.038) and non-dominant-hand impairment rates of 100% vs. 63.2% (p=0.043). Non-dominant GS was weaker in the HIV/stroke group (100% impaired vs. 47.4%; p=0.0014). Lower-limb performance was substantially worse, including TUG (median z-score -3.63 vs. 0.10; p=0.0001) and 10MWT (median z-score -5.36 vs. -2.47; p=0.0025). ADL scores were also lower in the HIV/stroke group compared to both Barthel and Lawton (p=0.002). Conclusions: HIV alone is associated with cognitive and motor impairment, with the addition of stroke producing significantly greater deficits across all motor domains. These findings demonstrate the need to integrate structured neurorehabilitation into HIV clinical care in Botswana.

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: Internalized HIV stigma remains a major psychosocial challenge for women living with HIV (WLHIV) and may adversely affect antiretroviral therapy (ART) adherence and health-related quality of life (HRQoL). However, fewer studies in sub-Saharan Africa have examined how internalized stigma and ART adherence jointly relate to multidimensional HRQoL among WLHIV receiving routine HIV care. This study examined the associations of internalized HIV stigma and ART adherence with HRQoL among WLHIV in Lagos, Nigeria, and explored whether the relationship between stigma and HRQoL varied by ART adherence status. Methods: This was a baseline analytical study nested within a quasi-experimental study among WLHIV receiving care at the HIV Treatment Centre of the Nigerian Institute of Medical Research, Lagos, Nigeria. The analysis included 1,005 women with complete baseline data on internalized stigma, ART adherence, HRQoL, and selected covariates. Internalized stigma was assessed using the 10-item Internalized Stigma of HIV/AIDS Tool and categorized as low or high using the sample median. ART adherence was measured using pharmacy refill adherence and self-reported adherence, which were combined into a composite overall adherence variable. HRQoL was assessed using the WHOQOL-HIV BREF, and the primary outcome was the total domain-based quality-of-life score derived from the six WHOQOL-HIV domains. Linear regression was used to examine associations between stigma and adherence and the total domain-based QoL score, and an interaction term between internalized stigma and overall ART adherence was included to assess effect modification. Results: The mean age of participants was 47.8 years (SD 12.5), and 56.0% had high levels of internalized stigma. Overall, 73.3% were classified as adherent using the composite ART adherence measure. HRQoL was consistently poorer among women with high internalized stigma across all WHOQOL-HIV BREF domains. Women with high internalized stigma had a substantially lower total domain-based QoL score than those with low stigma (106.5; SD 11.0 vs 117.8; SD 10.6; p < 0.001). In the final multivariable model, high internalized stigma remained the strongest independent correlate of lower QoL ({beta} = -10.07, 95% CI: -11.41 to -8.73; p < 0.001), while overall ART non-adherence was also associated with lower QoL ({beta} = -2.78, 95% CI: -4.24 to -1.33; p < 0.001). Older age and living more than 5 km from the health facility were associated with lower QoL, whereas social support was associated with higher QoL. Interaction analyses showed that predicted QoL was highest among women with low stigma who were adherent and lowest among those with high stigma who were non-adherent. Conclusions: Internalized HIV stigma and ART non-adherence were independently associated with poorer HRQoL among WLHIV in Lagos, Nigeria. Internalized stigma emerged as the strongest correlate of poorer well-being, underscoring the need to move beyond narrowly biomedical models of HIV care. Interventions that integrate stigma reduction, adherence support, and psychosocial strengthening may be particularly valuable for improving patient-centered outcomes among WLHIV in routine HIV care settings.

Since its inception in 2003, the United States President's Emergency Plan for AIDS Relief (PEPFAR) has played a central role in HIV/AIDS prevention and treatment across Sub-Saharan Africa. Following the January 2025 suspension of United States foreign aid, which includes PEPFAR funding, countries across Sub-Saharan Africa demonstrated varying governmental responses to the resulting HIV funding disruptions. This study evaluates whether national characteristics were associated with a country's ability to respond to this funding crisis. Countries in Sub-Saharan Africa receiving PEPFAR funding were classified into one of three response categories: Level 1 (minimal or no governmental response), Level 2 (government response without sufficient plans or resources to fully offset funding losses), or Level 3 (high governmental response with strategies to maintain HIV/AIDS prevention and treatment services). Response categories were compared with national Human Development Index (HDI), GDP per capita, HIV prevalence, total population living with HIV, annual HIV mortality, and historical PEPFAR funding. Univariable proportional-odds ordinal logistic regression was used to identify factors associated with response level. Five countries (17.2%) were classified as Level 1, 10 (34.5%) as Level 2, and 14 (48.3%) as Level 3. Higher HDI was significantly associated with stronger governmental response (OR = 4.05; 95% CI, 1.49-11.04; Holm-adjusted p = 0.0376). GDP per capita (OR = 2.35; 95% CI, 1.00-5.51; unadjusted p = 0.0489) and HIV prevalence (OR = 3.53; 95% CI, 1.03-12.11; unadjusted p = 0.0452) demonstrated positive associations before adjustment for multiple comparisons, but neither remained significant after Holm correction (adjusted p = 0.2261 for both). Historical PEPFAR funding, total population living with HIV, and annual HIV mortality were not significantly associated with response level after adjustment. Countries with higher levels of human development demonstrated stronger governmental responses to the 2025 PEPFAR funding disruptions. Several countries with minimal documented responses were also affected by active conflict or political instability, potentially compounding their vulnerability to treatment interruptions. These findings suggest that broader national development may play an important role in governmental responses to funding disruptions and highlight the need to strengthen resilient health systems, diversify HIV financing, and prioritize support for countries at greatest risk of future funding shocks.

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.

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.

Dendritic cells (DCs) are central orchestrators of antiviral immunity but can be exploited by HIV-1 to facilitate systemic dissemination. HIV-1 recognition by CD169 triggers massive endocytosis (MEND)-related internalization of viral particles into sac-like compartments in monocyte-derived dendritic cells (MDDCs), thereby promoting trans-infection of CD4+ T cells. However, MDDCS represent only one DC subpopulation, and whether other physiologically relevant DC subsets exhibit similar behavior remains unclear. Moreover, endogenous CD169 expression and viral capture have not been fully characterized in cDC1, DC2, or pDCs, while remain unknown in DC3. We therefore investigated the contribution of these DC subsets to CD169-mediated HIV-1 capture and subsequent viral dissemination. We used flow cytometry to assess CD169 expression and viral capture across DC subsets differentiated from CD34 hematopoietic stem and progenitor cells (HSPC) obtained from bone marrow (BM) and cord blood (CB), two sources that differ in cellular maturity. Confocal microscopy was used to evaluate sac-like compartment formation following immune activation with IFN- or LPS and treatment with MEND inhibitors. Trans-infection capacity was quantified by measuring luciferase activity in TZM-bl reporter cells. We identified cDC1, DC2, DC3, moDC (similar to MDDCs), and pDC subsets following the differentiation of CD34 HSPC from both CB and BM. Among these populations, DC2, DC3, and moDC displayed high CD169 expression, which was significantly upregulated by IFN- or LPS stimulation. BM-derived DCs exhibited higher basal CD169 expression than CB-derived DCs, whereas stimulation induced greater CD169 upregulation in CB-derived DCs. DC2, DC3, and moDC efficiently captured HIV-1 particles in cultures derived from both sources, and viral uptake was further enhanced by immune activation. Viral internalization into sac-like compartments depended on CD169 binding and MEND-related mechanisms, ultimately facilitating HIV-1 transfer to target cells. DC2 and DC3 are key dendritic cell subsets that support CD169 dependent HIV-1 capture and are associated with MEND-driven internalization into sac-like compartments and subsequent viral transfer to target cells, as was previously described for moDCs. We further observed distinct basal and inducible CD169 expression profiles in BM- and CB-derived DCs, consistent with source-dependent maturation states. These results identify DC2 and DC3 as key cellular contributors to HIV-1 dissemination.

The efficacy of current antiretroviral interventions for prevention of vertical HIV transmission is both a triumph and a challenge for future efficacy studies of novel agents, including long-acting antiretroviral agents. Given the effectiveness of current antiretroviral interventions, standard randomized controlled trials to assess novel interventions targeted towards further reducing vertical HIV transmission may be infeasible due to required sample sizes. To address this study design challenge, we propose a novel augmented clinical trial design, where a randomized trial with an active comparator is augmented with a concurrent observational cohort to supplement the standard-of-care arm. The proposed design and analysis can overcome sampling biases, and an associated diagnostic can evaluate potential biases from unmeasured covariates. The proposed trial design is illustrated with an example and studied further using a simulation study. In the illustrative example, an augmented trial with a 3:1 allocation ratio in the trial component yielded an unbiased treatment effect estimate, as compared to the trial component alone, and the standard error was reduced substantially. Although the total sample size of the augmented trial was larger than a similarly powered 1:1 standard trial, the sample size of the augmented trial's trial component was half the size of the standard trial and within the range of historically similar trials, thereby providing both feasibility and potential cost advantages. Although limitations with this design remain, many of these limitations can be mitigated by careful study planning and coordination. Augmented trials provide a potentially applicable solution to studying the efficacy of long-acting antiretrovirals for infant postnatal prophylaxis against HIV.

Abstract Background: Chronic subdural hematoma (cSDH) remains a significant and increasingly prevalent cause of morbidity in older adults. Disease progression is sustained by de novo formed highly vascularized pseudomembranes and a persistent cycle of fluid accumulation and hematoma expansion. Although inflammatory and angiogenic pathways have been implicated in cSDH pathogenesis, the endothelial mechanisms underlying persistent vascular leak remain poorly understood. We investigated the cSDH vascular microenvironment in human patients and examined the role of vascular endothelial cadherin (VECAD) remodeling in cSDH endothelial dysfunction. Methods: Human cSDH membranes and fluid were evaluated by multiplex profiling, histology, immunofluorescence, immunoprecipitation, western blotting and exploratory bulk RNA sequencing. A human brain endothelial cell (HBEC) line was exposed to patient-derived cSDH fluid to assess VECAD remodeling, endothelial barrier permeability, and proliferation. Results: Multiplex profiling of patient-derived cSDH fluid detected mediators associated with endothelial cell (EC) activation, extracellular matrix remodeling, inflammation, and angiogenesis. In patient pseudomembranes, discontinuous VECAD coincided with erythrocyte extravasation. Two hyperdense (high-risk) specimens showed more extensive disruption than the hypodense (low-risk) specimen while vessel counts appeared similar. Bulk RNA sequencing identified an angiogenic environment and enrichment in cadherin regulation. A soluble VECAD (sVECAD) isoform was detected in cSDH fluid. Exposure of HBECs to patient-derived cSDH fluid increased EC proliferation, cytoplasmic VECAD (cVECAD) accumulation, and EC barrier permeability. Concurrent dexamethasone or minocycline treatment attenuated VECAD cleavage. Conclusions: VECAD disruption is a prominent feature of cSDH and is associated with EC barrier dysfunction. These findings support further evaluation of soluble VECAD as a candidate biomarker and of junction-preserving pathways as potential therapeutic targets.

In resource-limited settings plasma is usually transported to centralized laboratories for HIV RNA quantification; often by motor vehicles using dry ice. Any decay in plasma HIV RNA when near the threshold used to define virologic failure could impact clinical management. However, maintaining a cold chain during transport can be costly and limit the frequency of shipments, which can delay clinical assessments and also negatively impact patient care. Transporting plasma at ambient temperatures could facilitate timely measurements of plasma HIV RNA viral loads (VL). We conducted a stability study of HIV RNA in plasma held for 1, 3, 5, and 7 days at a range of temperatures (4{degrees}C, 30{degrees}C, and 37{degrees}C) to simulate the durations and temperatures specimens could experience during transport. Thirteen large volume plasma specimens with VL ranging from 2.7-5.53 log10 copies/mL were evaluated. Mean changes in VL between Day-0 to Day-1, Day-3, Day-5 or Day-7 were calculated, with decays >0.5 log10 c/mL considered clinically relevant. Compared to Day 0, the VL of plasma stored at 4{degrees}C and 30{degrees}C remained stable across the Days tested. The VL in plasma stored at 37{degrees}C had a progressive decline at Day-1, Day-3, Day-5 and Day-7 (means of -0.04, -0.19, -0.33. -0.34 log10 c/mL, respectively), with a decay of >0.5 log10 observed in 3/13 (23%) specimens at Day-7. A linear regression analysis showed that plasma specimens stored at 37{degrees}C significantly decayed over time (slope -0.054, 95% CI -0.079, -0.029; p=0.01). Any decay observed among specimens stored at 4{degrees}C and 30{degrees}C was not clinically relevant nor statistically significant. Our observations suggest that HIV RNA levels in plasma should remain stable if transported to centralized laboratories at ambient temperatures of [&le;]30{degrees}C or chilled by cold packs over a period [&le;]7 days. Transporting specimens with cold packs instead of dry ice could reduce costs and facilitate the timely monitoring of VL used to assess and guide antiretroviral therapy.

Background Long-acting HIV pre-exposure prophylaxis (LAP) could transform HIV prevention in sub-Saharan Africa, but its public-health impact and value-for-money will depend on whether programmes can reach people at greatest risk. We quantified the potential impact and efficiency of targeted LAP deployment across sub-Saharan Africa. Methods We developed a deterministic, age-structured compartmental model of HIV among adults aged 15 years or older in African countries accounting for 98% of adults living with HIV in sub-Saharan Africa. Antiretroviral therapy (ART) was assumed to reach 95% coverage by 2030 in all countries. LAP was assumed to reduce HIV acquisition by 96%. In model analyses, LAP was allocated according to rules that specify the degree to which programmes can effectively allocate it to those at greatest risk of acquiring HIV, including using a person's district, sex and age-group, and other signals of risk. Findings Across 34 countries, allocating a fixed quantity of LAP by district, sex and age averted 2 - 21 times as many infections as uniform allocation; perfect identification of within-group risk, an upper bound, raised this to 5 - 32 times. Multipliers were largest in low-prevalence countries, where absolute impact was smallest; in higher burden settings, they were 2 - 6 and 5 - 11, respectively. If 3 million people used LAP from 2028 in the 11 countries currently receiving Global Fund-supported lenacapavir, uniform allocation would avert about 41,000 infections by 2050, targeting by district, sex and age about 601,000 (range 360,000 - 1,660,000), and perfect risk targeting about 972,000 (490,000 - 3,570,000). Discounted averted ART costs fully offset LAP costs by 2050 at a total cost of up to ~US$50 per person-year with perfect risk targeting, $30 with targeting by district, sex and age, and $2 with uniform allocation. Expansion to 15 million users by 2035 brought modelled adult incidence across sub-Saharan Africa below 0.1 per 1000 person-years in 2049, about a decade earlier than projected without LAP, under the assumption that ART coverage reaches 95% in every country by 2030. Interpretation Targeting determines both the impact and the net cost of LAP. Allocation by district, sex and age is feasible now and multiplies the infections averted by each person-year of LAP. LAP offsets its cost through averted treatment only when it is targeted and its fully loaded cost is near the low end of current estimates. Better identification of people at highest risk within demographic groups, and sustained use among them, could add substantially to impact. The same approach could guide the allocation of LAP in other settings where HIV risk is concentrated.

Background: Treponema pallidum quantitative polymerase chain reaction (qPCR) positivity and cycle threshold (Ct) by rapid plasma reagin (RPR), disease stage, and other characteristics are poorly characterized in routine-care specimens, leaving it unclear when qPCR of such specimens is informative for diagnosis. Methods: This Japanese multicenter cross-sectional study explored qPCR positivity and Ct by these characteristics. Nonblood specimens collected during routine care underwent qPCR at a central laboratory for this study. Bayesian logistic and normal regressions modeled positivity and mean Ct of TP0574 and polA with stage-specific continuous automated RPR terms, patient characteristics, collection site, and facility random intercepts. Estimates were standardized over the analyzed specimens. Population-group predictions were instead averaged within each group. Results: Among 154 nonblood specimens from 145 patients (71.7% non-MSM men and women) at 14 facilities, 109 (70.8%) were qPCR positive. At RPR 1, adjusted positivity was 72.2% (95% credible interval, 60.9%--82.9%) in primary and 43.8% (16.7%--69.9%) in secondary syphilis. Positivity showed a modest downward trend with RPR in primary but increased in secondary syphilis, reflecting a stage-by-RPR interaction (secondary-to-primary ratio of odds ratios, 1.78; 1.25--2.65). Predicted positivity showed an upward trend with RPR values among MSM; adjusted positivity was relatively high for genital/urethral/urinary and anal/perianal/rectal specimens. Adjusted mean Ct increased with RPR in primary and followed an inverted-U pattern in secondary syphilis. Conclusions: In primary syphilis, nonblood qPCR positivity was high even at low RPR. When serologic findings remain inconclusive in this stage, qPCR is highly recommended for securing an early diagnosis.

Background Community-led interventions for female sex workers (FSW) can improve HIV prevention and treatment outcomes by lowering self-stigma and strengthening social cohesion to improve service uptake. In Zimbabwe, the AMETHIST intervention trial integrated peer-led microplanning with self-help groups for FSW and demonstrated improved HIV treatment outcomes. We investigated the role of social cohesion and self-stigma in explaining these findings. Method We conducted a mixed-method analysis of data collected during AMETHIST. We re-analysed qualitative data from interviews and group discussions to identify narratives linking self-stigma, engagement with microplanners and/or self-help groups and HIV service use. We analysed quantitative data from endline respondent-driven sampling surveys for differences in self-reported measures of social cohesion and self-stigma between trial arms, and between those who did and did not participate in intervention activities or access services. Results In both arms, FSW self-reported engaging with peer supporters, participating in self-help groups and accessing HIV services. Qualitative narratives suggested peer support and group participation could reduce self-stigma and support service uptake. Lower levels of self-stigma were seen in the intervention arm (58.6% vs 63.2%; aOR 0.77; 95% CI 0.61-0.86). Social cohesion exceeded 50% across the whole sample, but was not associated with study arm, nor with engagement in intervention-related activities. Discussion Although qualitative data suggested some FSW felt their uptake of services was influenced by intervention components, quantitative analyses did not suggest either variable was on the causal pathway to the outcomes of the intervention. A limitation may have been the measurement of these complex constructs and the high levels of social cohesion across both study arms.

Introduction: HIV and childhood maltreatment (CM) are both chronic stressors that disproportionately affect women, with each contributing to accelerated biological aging. Whether biological aging markers are convergent and associate with HIV and CM is unclear. Methods: We studied 238 women (122 with HIV), characterised for CM severity, and assessed biological aging using absolute telomere length (aTL), mitochondrial DNA copy number (mtDNAcn), magnetic resonance imaging-based brain-predicted age difference (MRI-BPAD), and DNA methylation age (DNAmAge) clocks. CM was measured with the Childhood Trauma Questionnaire-Short Form total score. We examined intercorrelations among biological aging markers to assess convergence and conducted linear regression models to test moderation by HIV status and CM severity. Results: PWH had shorter aTL, lower MRI-BPAD, and higher Horvath age acceleration (HorvathAA), HannumAA, PhenoAA, and extrinsic epigenetic age acceleration (EEAA). CM had limited associations with biological aging markers. Absolute TL correlated weakly with mtDNAcn (p = 0.36), PhenoAA (p = -0.18), and EEAA (p = -0.18), while MRI-BPAD correlated weakly with PhenoAA (r = 0.20). DNAmAge clocks were moderately to strongly intercorrelated (r = 0.35 - 0.93). No robust two- or three-way moderation effects were observed after false discovery rate correction. Conclusion: Our findings support a multidimensional pattern of biological aging, with substantial convergence among epigenetic aging measures but limited relationships across different markers, largely independent of HIV status and CM severity. Longitudinal approaches are needed to clarify how distinct biological aging markers relate to one another and to health outcomes over time in vulnerable populations.

Background Sustained retention in HIV care is essential for maintaining antiretroviral therapy (ART) and achieving viral suppression. We described national and regional retention in HIV care among paediatric and adolescent ART initiation cohorts in Uganda from 2020-2023. Methods We analyzed aggregated paediatric (aged 0-9 years) and adolescent (aged 10-19 years) ART cohort data reported through the District Health Information Software. We assessed 16 consecutive quarterly ART initiation cohorts per age group, from Quarter 1 2020 to Quarter 4 2023, at 6 (short-term), 12 (intermediate), and 24 (long-term) months after ART initiation. Each cohort comprised clients newly initiated on ART in a specific calendar quarter. Retention was defined as the proportion of clients alive and on ART within the net current cohort (original cohort plus transfer-ins minus transfer-outs). We described retention nationally and by region for each cohort and follow-up time point. We summarized the proportion of cohorts with retention [&ge;]95% by region as a descriptive measure of high retention. Results Among paediatric cohorts, median retention was 84% (IQR: 82-85%) at 6 months, 81% (IQR: 78-83%) at 12 months, and 78% (IQR: 75-80%) at 24 months. Only one national paediatric cohort achieved [&ge;]95% retention at 6 months and one at 12 months; none attained this target at 24 months. The proportion of paediatric cohorts with regional retention [&ge;]95% was highest in Karamoja at short-term follow-up (31%), in Kigezi at intermediate follow-up (31%), and in Lango at long-term follow-up (13%). Among adolescent cohorts, median retention was 82% (IQR: 80-85%) at 6 months, 82% (IQR: 81-85%) at 12 months, and 76% (IQR: 74-78%) at 24 months. No national adolescent cohort achieved [&ge;]95% retention. The proportion of adolescent cohorts with regional retention [&ge;]95% was highest in West Nile at 6 months (19%) and 12 months (31%), and in Karamoja at 24 months (25%). Conclusion Retention among paediatric and adolescent ART cohorts declined with longer follow-up and varied across regions. Strengthening age-appropriate support beyond the first year of ART and improving routine cohort-data quality could support more targeted programme responses.

Background The abrupt withdrawal and uneven restoration of United States PEPFAR support in 2025 disrupted HIV service delivery in aid-dependent countries worldwide. In Zambia, decreases in HIV service delivery have been documented at a national level, but variations by facility and by quarter have largely been masked by existing aggregate district- and province-level estimates. We examined facility-level variation in HIV service volumes delivered before and after the funding cuts. Methods We analysed monthly District Health Information System (DHIS2) data covering testing volumes, ART initiations, and numbers on ART for January 2024-December 2025) for two sets of facilities: 1) 24 selected SENTINEL network facilities across four provinces (Central, Copperbelt, Lusaka, and Southern); and 2) all facilities in two districts, Chongwe in Lusaka Province, which was supported by the U.S. CDC under PEPFAR, and Mpongwe in Copperbelt Province, which was supported by USAID under PEPFAR. For each facility, we calculated quarterly 2025:2024 ratios of service volumes and summarized quarterly and annual percentage changes in numbers of tests, treatment initiations, and clients on ART. Results Aggregate HIV testing volumes declined 18% in SENTINEL facilities from 2024 to 2025, with 17 of 24 facilities showing net annual decreases. Aggregate ART initiations declined 16%, with 23 of 24 facilities experiencing net decreases. For both indicators, variation between quarters and among individual facilities matched or exceeded aggregate changes. Numbers of clients currently on ART were comparatively stable, with only 6 facilities showing net declines exceeding 5%. District-level analyses showed divergent patterns. Net aggregate testing volumes increased by 7% in Chongwe District, but 28/39 facilities experienced quarterly declines exceeding 10% in at least one quarter and fell by 40% in Mpongwe District overall. Only 4 of 36 sites in Chongwe showed a net loss of clients over the course of 2025, with most experiencing gains, while Mpongwe experienced substantial variation by facility, with many having declines of >30% during some quarters and 14 of the 25 facilities suffering a net loss from 2024 to 2025. Conclusions Facility-level performance varied substantially within the same district following the 2025 PEPFAR funding disruptions, with some sites losing most of their service volumes while others remained stable or exceeded 2024 levels. These findings emphasize the need for facility-level monitoring to target recovery support where it is needed most.