JAIDS Journal of Acquired Immune Deficiency Syndromes

Background African immigrants in the United States bear a disproportionate HIV burden, with incidence approximately sixfold higher than the general population, yet remain largely absent from targeted prevention research. HIV vulnerability among this population is mediated through relationship and family systems that are restructured by migration, reorganizing household composition, gender norms, trust, and communication patterns through which prevention engagement occurs. Despite this, migration has rarely been examined as a force that transforms the relational contexts shaping engagement with HIV testing, HIV self-testing (HIVST), and pre-exposure prophylaxis (PrEP). Methods The MiST-Pathways Study will use a sequential mixed-methods, community-based pilot design among first-generation African immigrant adults (ages 18-50) residing in New York and Massachusetts. The study will proceed in three phases: Aim 1 will use semi-structured interviews (n = 15) and a structured survey (n = 75) to identify relationship typologies and migration-related relational mechanisms influencing HIV prevention engagement; Aim 2 will employ Palava Hut Conversations (PHC) (an African-centered deliberative method) with up to 30 participants to co-develop and prioritize relationship-tailored intervention components; and Aim 3 will conduct a proof-of-concept assessment of the prioritized component using a single-group pre-post design (n = 24), incorporating surveys and cognitive interviews to assess feasibility, acceptability, and preliminary evidence of mechanism activation. All activities will be conducted virtually via Zoom and WhatsApp, with eligibility screening administered through REDCap. The study has been approved by the University at Buffalo Institutional Review Board (STUDY00010347) and registered at ClinicalTrials.gov (NCT07565584). Discussion This protocol outlines the planned evaluation of a sequentially designed, community-engaged pilot study to examine how migration reshapes relational contexts that influence HIV prevention decision-making among African immigrants. Findings will inform the development of culturally grounded, relationship-tailored prevention strategies and the design of a future, larger-scale intervention study.

In the United States, gay, bisexual, and other men who have sex with men (MSM) experience a disproportionate burden of sexually transmitted infections (STIs), with notable racial/ethnic disparities. Doxycycline post-exposure prophylaxis (doxy-PEP) has emerged as a promising strategy to prevent bacterial STIs. This study analyzed 2023 National HIV Behavioral Surveillance data to examine doxy-PEP awareness, use, and intent to use among MSM in New York City (NYC), in a predominantly Hispanic/Latino sample. Among 134 participants, awareness and prior use were low (38.8% and 9.0%, respectively), but intent to use was high (75.4%). In Poisson regression models, intent was higher among participants reporting non-injection drug use and 2-10 partners in the past 12 months, while marginally lower among those above the Federal Poverty Level and recent migrants. Findings suggest doxy-PEP is acceptable for MSM in NYC, but addressing barriers among low-income groups and recent migrants is critical to reducing disparities.

Background: Pre-exposure prophylaxis (PrEP) has demonstrated a significant reduction in HIV infections among men who have sex with men (MSM), however, low medication adherence hinders its preventative effectiveness. Traditional approaches, such as health education and face-to-face inquiry (HEF), have demonstrated certain efficacy in improving PrEP adherence. However, these methods are resource-intensive and often plagued by delays, rendering timely and precise interventions challenging. This randomized controlled trial aims to assess the effectiveness of an intervention comprising AI-chatbot for PrEP (PrEP-bot) and Smart pillbox (SPB) (PrEP-bot-SPB) strategy to improve PrEP adherence among MSM compared to HEF.Methods and analysis: A three-arm, multicenter, open-lable RCT will be conducted with Chinese MSM [≥]18 years. A total of 300 participants will be recruited through three sources, including hospitals, community-based organizations (CBOs) and peer referral in five cities: Shenzhen, Beijing, Qingdao, Hangzhou and Zhengzhou. After completing baseline survey, participants will be randomized evenly into interventions or control groups: the PrEP-bot group, the PrEP-bot-SPB group, and the HEF control group. Participants in the PrEP-bot group will be granted access to an AI-chatbot agent through WeChat. This agent will: 1) generate personalized PrEP medication plans; 2) provide medication reminders and PrEP-related health check-ups notifications; 3) inquire about missed doses to deliver tailored interventions; 4) answer participant questions about PrEP using guideline-based knowledge. Participants in the PrEP-bot-SPB group will receive both the SPB and the PrEP-bot interventions. SPB could delivers medication reminders. Participants in HEF group will receive a health education pamphlet introducing PrEP and knowledge related to PrEP medication adherence at baseline and face-to-face inquiry every three months. Outcomes will be assessed for both short-term and medium-to-long-term effects. The primary objective is the effectiveness in improving PrEP adherence measured by self-report, Eight-Item Morisky medication adherence scale (MMAS-8) and concentration of Tenofovir in dried blood spots (DBS) (PrEP adherence [≥]90%) at 3 months follow-up. Secondary outcomes include: 1) effectiveness in preventing HIV infection measured by HIV-self test (HIVST); 2) effectiveness of PrEP-related health check-ups; 3) the effectiveness, feasibility, acceptability, and user satisfaction with the PrEP-bot; 4) effectiveness in improving PrEP adherence at 6-month, 9-month and 12-month follow-up periods. All participants will receive quarterly follow-up visits during the 12-month study period. Intention-to-treat analysis and per protocol set (PPS) analysis will be used.Results: Recruitment and enrollment of participants began in January 2026 and is currently ongoing.Discussion: This study is expected to establish a novel AI-based intervention model for PrEP, providing innovative strategies for HIV control among MSM populations. If the PrEP-bot is proven non-inferior to HEF, it could offer users real-time, precise, and personalized interventions while simultaneously addressing PrEP-related inquiries and health check-ups reminders. Importantly, this approach would achieve significant reductions in resource requirements for implementation and maintenance and be more cost-effective. With the ongoing advancement of AI technologies, PrEP-bot holds substantial promise for widespread implementation in PrEP adherence, potentially revolutionizing HIV prevention for MSM in China through this innovative intervention modality.Trial registration: ChiCTR2500111280 (Chinese Clinical Trial Registry). Date of registration: 29 October 2025.

BackgroundHIV-related stigma remains a primary barrier to the elimination of the HIV epidemic worldwide. No studies have examined long-term changes in the distribution of stigmatizing attitudes within populations. MethodsWe conducted a whole-population, open cohort study of adults in 8 villages in rural southwestern Uganda, with 5 biennial surveys spanning 2014-2024 (N=1,776 at baseline; 869 participated in all waves). We measured individual negative attitudes toward people with HIV ("public stigma") and perceptions of negative attitudes among others ("perceived stigma") using parallel 15-item scales. We estimated mean stigma scores, computed inequality measures at each wave, and decomposed inequality by sociodemographic characteristics. Leveraging the cohort design, we estimated intraclass correlation coefficients and rank-order stability over time. ResultsBoth public and perceived stigma declined substantially from baseline to endline and became concentrated in an increasingly smaller subgroup of the population. Theil decomposition failed to identify any stratifying variables that explained more than 3% of this variation: nearly all the inequality in HIV stigma occurred within population subgroups rather than between them. In longitudinal analyses, public stigma showed trait-like properties (intraclass correlation coefficient=0.35; 95% CI, 0.31-0.38) and meaningful rank-order stability (baseline-to-endline r=0.41). Perceived stigma showed no rank-order stability, no appreciable between-person variance, and universal convergence to low levels regardless of baseline. ConclusionsBoth public and perceived HIV stigma declined substantially in this rural Ugandan population, but remaining public stigma has become concentrated within a persistent minority. Sociodemographic profiling to target individuals who carry persistently negative attitudes toward people with HIV is unlikely to succeed.

Introduction Viral load monitoring is central to assessing antiretroviral therapy (ART) effectiveness, yet timely access remains challenging in resource-constrained settings. Point-of-care (POC) triage tests may improve ART monitoring efficiency by identifying clients requiring confirmatory viral load testing while reducing unnecessary testing among those likely to be virally suppressed. We explored perceptions of integrating a POC triage test that measures interferon-gamma-induced protein 10 (IP-10) - a chemokine strongly correlated with HIV viral load - into routine ART monitoring among people living with HIV (PLHIV) on ART, healthcare providers, and HIV programme stakeholders. Methods This qualitative study was nested within a clinical evaluation of the IP-10 POC triage test in two primary healthcare facilities in Maputo Province, Mozambique (2023-2024). We conducted three rounds of interviews with PLHIV on ART who underwent IP-10 testing, and one-off interviews with healthcare providers and HIV programme stakeholders across different health system levels. PLHIV were purposively sampled to capture diverse IP-10 and viral load outcomes. Interviews explored experiences of ART monitoring, perceptions of the IP-10 POC test, and implementation considerations. Data were analysed thematically using an inductive-deductive approach. Results Routine viral load monitoring was widely valued and understood as essential for treatment adherence and effectiveness, but participants described barriers including laboratory delays, access challenges, and health system constraints. The IP-10 POC triage test was broadly acceptable; same-day results were perceived to reduce anxiety, support adherence, and enable timely clinical decision-making. Providers and stakeholders emphasised its potential to improve monitoring efficiency by prioritising clients who require confirmatory viral load testing and adherence support. Concerns were raised regarding test accuracy and the need to maintain confirmatory viral load testing, underscoring the importance of clear communication and client education. Successful implementation would require training, workflow integration, and quality assurance. Conclusions An IP-10 POC triage test could strengthen ART monitoring by enabling same-day identification of clients requiring confirmatory viral load testing and targeted adherence support. By reducing unnecessary viral load testing for virally suppressed clients, it may contribute to more efficient monitoring and support differentiated care approaches. Careful integration into existing ART monitoring algorithms will be critical to maximise impact.

Delayed diagnosis and poor antiretroviral therapy (ART) adherence remain primary drivers of HIV-related morbidity in low-resource settings, yet real-world AI validation at scale is lacking. We conducted a retrospective validation study using two publicly available, de-identified datasets: a Quality of Care cohort of 27,288 HIV-positive patients on ART across multiple healthcare facilities, and the CEPHIA multi-country assay database comprising 165,444 specimen records from six countries. Four machine learning classifiers were evaluated using 10-fold stratified cross-validation with SMOTE applied strictly to training folds. Explicit data leakage prevention, ablation analysis, calibration assessment, and bootstrap confidence intervals were applied. Economic projections used one-way sensitivity analysis. This study adheres to TRIPOD reporting guidelines. Random Forest achieved AUC-ROC of 0.9753 (95% CI: 0.970-0.975), sensitivity 87.3% (95% CI: 86.4-88.2%), specificity 95.7% (95% CI: 95.2-96.2%), and Brier score 0.079. Ablation testing confirmed robustness (AUC 0.963 without the primary predictor). Temporal validation on held-out future patients yielded AUC 0.772 (95% CI: 0.744-0.802), confirming generalisation across time. Real-world analysis revealed median diagnosis-to-ART delay of 74 days, with 47.3% of patients exceeding 90 days and 36.7% presenting with CD4 below 200 cells per microlitre. Multi-country CEPHIA analysis identified 18.6% HIV recency within the 130-day early-intervention window. Decision curve analysis confirmed net clinical benefit across threshold probabilities 0.03-0.45. Subgroup analysis demonstrated consistent AUC across sex, age, CD4 strata, and WHO staging (max difference 0.051). Economic modelling projected base-case savings of USD 415 per patient (USD 2.07 million per 5,000-patient cohort). These findings provide large-scale empirical evidence that AI-driven informatics can predict ART adherence failure and quantify systemic care gaps, offering a scalable framework for equitable HIV care delivery in resource-limited settings. Prospective external validation is required before clinical deployment.

Background: Long-acting pre-exposure prophylaxis (PrEP) expands HIV prevention options for women. However, PrEP impact depends on addressing persistent gaps in awareness, access, and use. Artificial intelligence (AI) tools, including conversational agents, are being explored to advance PrEP uptake, but comfort with AI may influence their impact. Thus, we examined women's comfort with AI and its association with PrEP awareness. Methods: We analyzed self-reported data from women aged [≥]18 years in a cross-sectional survey conducted in New York City from August 2023 to August 2024. We performed descriptive analyses, applied latent class analysis to identify AI knowledge/comfort profiles, and estimated unadjusted and adjusted odds ratios to assess associations between profile membership and PrEP awareness. Results: Among 306 respondents without a diagnosis of HIV who completed AI-related survey items, the median age was 36. Most women identified as Hispanic/Latina (60%) or Non-Hispanic Black (18%), had not completed college (53%), and spoke only English or were bilingual (81%). Latent class analysis identified four AI knowledge/comfort profiles that differed by PrEP awareness, race/ethnicity, borough, prior drug use, and technology utilization. Women with varied AI knowledge, broad AI discomfort, and comfort with clinicians maintaining privacy had lower odds of PrEP awareness (OR: 0.35, 95% CI: 0.16-0.75), but this association did not persist after statistical adjustment. Conclusions: PrEP awareness and AI knowledge were limited, yet many women expressed openness to AI-enabled tools when privacy was assured. AI-enabled HIV prevention tools should prioritize trust, transparency, confidentiality, and the lived contexts of the women they intend to serve.

Background Studies show 53 to 74% of women living with HIV experience postpartum ART adherence challenges. Viral load testing is a delayed indicator, highlighting the need for culturally appropriate screening tools to identify at-risk women early. This study examined the association between non-viral suppression and constructs within the AIDS Clinical Trials Group (ACTG) adherence questionnaire among women in Uganda to inform timely, targeted interventions to improve adherence. Methods The ACTG was adapted, and postpartum participants completed ACASI or Provider-Assisted Interviews (PAIs). Self-efficacy, social support, anxiety, depression, viral load, and clinical factors were analysed using mixed-effects logistic models over a 1-year period. Results Of 166 women, 21 completed ACASI and 145 PAIs. 4.2% (7/166) were not virally suppressed at baseline, and their non-suppression status was consistent throughout one year of follow-up. High self-efficacy scores were associated with 27% lower odds of viral non-suppression (Odds Ratio [OR], 0.73; 95% CI, 0.54, 0.98). High depression scores were associated with 22% higher odds of non-suppression (OR 1.22;95% (1.01,1.49). Other variables, including age, Body Mass Index, duration on ART, marital status, employment, education level, tap water, and travel time from home to clinic, were not associated with viral suppression in the covariate-adjusted analyses. Median self-efficacy and depression scores were 8 (IQR 1,9) and 1.2 (IQR 0,16), respectively. Focused group discussion data showed high acceptability and feasibility of using the ACTG adherence questionnaire in Uganda. Conclusion Lower self-efficacy and higher depression scores on the ACTG adherence questionnaire can help identify Ugandan women at risk of viral non-suppression in HIV programs. Keywords WLHIV, Antiretroviral Therapy, Adherence, Audio Computer Assisted Self Interview, Viral load

Introduction: Differentiated service delivery (DSD) models aim to reduce time healthcare providers spend with DSD clients, increasing time available for non-DSD clients. We measured nurses' time allocation and explored their experiences with DSD models in South Africa. Methods: We conducted time and motion observations and surveyed nurses at 24 public primary healthcare facilities across two SENTINEL study rounds (09/2022-07/2023 and 11/2023-07/2024). We report median time nurses spent by activity, model of care, and interaction type. Log binomial regression investigated factors associated with high direct nurse-client interaction (above median minutes) and extended work-days ([&ge;]9 hours), and estimated adjusted risk ratios (aRR). Survey questions were related to client care, additional time availability, and policy changes post DSD implementation, with key themes presented alongside illustrative quotes. Results: 176 nurses (88% female, median age 44) were observed for 344 working days; of these, 60 (34%) participated in the provider survey. Nurses spent a median of 293 minutes (53% of their work-day) on direct nurse-client interaction, 89 minutes (22%) on client-support or facility-related tasks, and the remainder on other activities including personal breaks. Time spent per client was similar across conventional care clients (11 [IQR: 8-15] minutes) but ranged between 9 (7-13) to 11 (8-15) minutes for DSD clients; number of direct nurse-client interactions did not differ meaningfully. Nurses at facilities with 2,000-3,999 total remaining on ART (TROA) (aRR 1.56, 95% CI: 1.02-2.37) and in urban areas (aRR 1.43, [1.08-1.89]) had more direct nurse-client interactions than those at facilities with <1,999 TROA and in rural areas, respectively. Nurses at facilities with 4,000+ TROA (aRR 2.22, [1.36-3.63]) and those observed in SENTINEL 3.0 (aRR 1.53, [1.13-2.07]) were more likely to work standard or longer workdays than those at lower TROA facilities (<1,999), those in SENTINEL 2.0 and urban areas. Nurses reported DSD models improved client care (90%), freed up time (60%), and changed clinic procedures and policies (60%). Conclusions: While DSD models did not significantly reduce direct nurse-client interaction time, nurses reported improved client care and gained additional time. DSD impact may vary by facility context. As DSD implementation expands, effective time reallocation may enhance facility performance and provider productivity.

Background: Advanced HIV disease (AHD) remains a major contributor to HIV-related morbidity and mortality despite widespread antiretroviral therapy (ART) access in sub-Saharan Africa. Although treatment-related adverse drug reactions (ADRs) may compromise treatment outcomes, evidence on the relationship between AHD and ADR occurrence remains limited. This study aimed to determine the prevalence and identify factors associated with AHD, characterize treatment-related ADR and assess the association between AHD and ADR occurrence among people living with HIV receiving ART in Dar es Salaam, Tanzania. Methods: We conducted a multicenter cross-sectional study among 1,513 people living with HIV receiving ART at selected HIV care and treatment clinics in Dar es Salaam, TanzaniaFor this adolescent/adult cohort, AHD was operationally defined as WHO clinical stage III/IV disease and/or baseline CD4 count <200 cells/mm3. Treatment-related ADRs were defined as participant-reported and/or clinically documented ART-related adverse events identified during routine HIV care, including both current and retrospectively reported events. Modified Poisson regression with robust standard errors was used to estimate crude and adjusted risk ratios (RRs) with 95% confidence intervals (CIs). Results: Among 1,508 participants with sufficient information for classification, 961 (63.7%) had AHD. Factors independently associated with AHD included age [&ge;]50 years (aRR 1.10, 95% CI 1.01-1.20), underweight nutritional status (aRR 1.17, 95% CI 1.00-1.35), and concomitant medication use (aRR 1.19, 95% CI 1.03-1.37), while DTG-based ART was associated with lower AHD prevalence (aRR 0.78, 95% CI 0.68-0.90). Overall, 569 participants (38.0%) reported at least one ADR. Composite AHD was not independently associated with ADR occurrence (aRR 0.95, 95% CI 0.82-1.11), but baseline CD4 <200 cells/mm3 was associated with increased ADR risk (aRR 1.20, 95% CI 1.02-1.41). Comorbidity (aRR 1.66, 95% CI 1.42-1.93) was the strongest correlate of ADR occurrence. Conclusion: AHD remains highly prevalent among people living with HIV receiving ART in Tanzania. While composite AHD was not independently associated with ADR occurrence, severe immunosuppression, comorbidity burden, and concomitant medication exposure were associated with increased ADR risk. These findings suggest that immunologic severity and broader clinical complexity may be more informative predictors of ART-related toxicity than composite syndromic AHD classification alone. Strengthened early diagnosis, differentiated advanced HIV care, integrated pharmacovigilance strategies, and routine medication risk assessment are needed.

Objectives: To examine COVID19 vaccine uptake among people diagnosed with sexually transmitted and bloodborne infections (STBBI) and reported methamphetamine users in Manitoba, Canada, during the acute phase of the COVID19 pandemic. Methods: We conducted a retrospective matched cohort study using linked population based administrative healthcare, laboratory, and vaccination databases in Manitoba. Individuals aged 16+ years with laboratory confirmed chlamydia/gonorrhea (CT/NG), syphilis, HIV, and/or documented methamphetamine use during the four years prior to March 1, 2020 were included in eight exposed cohorts. Each cohort was matched to unexposed comparators on age, sex, geographic region, and income quintile. The primary outcome was receipt of 2+ COVID19 vaccine doses between December 1, 2020 and March 31, 2022. Poisson regression models estimated adjusted rate ratios (aRRs) and 95% confidence intervals (95% CIs) for vaccine uptake. Results: Compared with matched comparators, most exposed cohorts were less likely to complete the COVID19 primary vaccine series. Individuals in the Syphilis Only (aRR: 0.87, 95% CI: 0.85 0.90), Syphilis Plus (aRR: 0.84, 95% CI: 0.81 0.86), CT/NG Only (aRR: 0.95, 95% CI: 0.94 0.96), CT/NG Plus (aRR: 0.82, 95% CI: 0.80 0.85), Methamphetamine Only (aRR: 0.78, 95% CI: 0.76 0.80), and Methamphetamine + STBBI cohorts (aRR: 0.74, 95% CI: 0.72 0.77) had significantly lower vaccine uptake. The HIV Only cohort did not differ significantly from matched comparators (aRR: 0.98, 95% CI: 0.95 1.01). Lower uptake was concentrated among individuals living in lower-income areas. Conclusions: People diagnosed with STBBI and methamphetamine users in Manitoba experienced significant inequities in COVID19 vaccine uptake, particularly those with STBBI coinfections and concurrent substance use. Integrated vaccination approaches linked with HIV, harm reduction, and addiction services may improve vaccine equity during future public health emergencies.

Introduction: Adolescent girls and young women (AGYW) in southern Africa are disproportionately affected by HIV. Despite increasing availability of HIV pre-exposure prophylaxis (PrEP), uptake and sustained use remain low. Existing service delivery models may not adequately meet the needs of AGYW, particularly in remote settings. We conducted a discrete choice experiment (DCE) to assess preferences for PrEP service delivery among AGYW living in Lesotho, a country with one of the highest HIV incidence rates globally. Methods: The DCE was conducted among AGYW (16-24 years) in two districts in Lesotho. Participants completed a series of binary choice tasks comparing hypothetical PrEP service delivery scenarios defined by six attributes: service location, provider type, provider characteristics, provider confidentiality, PrEP product type, and the combination of additional prevention services offered. Preferences were analysed using mixed logit and latent class models. Results: A total of 537 AGYW (median age 19 years, IQR 17-22) were included. Provider confidentiality was the strongest driver of choice, with non-confidential providers significantly less preferred ({beta} = -0.58; 95% CI -0.69 to -0.46). Compared with nurses, services delivered by ComBaCaL CHWs were preferred (0.17; 0.01 to 0.33), while those provided by doctors were less preferred (-0.15; -0.30 to 0.00). Younger female providers were preferred over older female providers (0.20; 0.04 to 0.36). Compared with the daily oral pill, both the 2-monthly injectable (-0.24; -0.39 to -0.08) and the vaginal ring (-1.02; -1.20 to -0.82) were less preferred. Differences in preferences were observed across age groups and districts. Latent class analysis identified two preference profiles, indicating variation in preferences for delivery and product characteristics. Conclusions: Preferences for PrEP delivery among AGYW in Lesotho were strongly influenced by provider confidentiality. Among some AGYW, there was openness to decentralised delivery, particularly through CHWs and community-based models, which may reduce access barriers in remote settings. Product preferences were varied, and not all options were acceptable. Differences by age group and district indicate that no single delivery model will meet all needs. Building on the current standard of care, offering acceptable options in accessible and confidential ways may support PrEP uptake.

Background: The isolation of many HIV broadly neutralizing antibodies (bnAbs) from people living with HIV (PLWH) and rigorous characterization of their ontogeny has promoted the goal of reverse engineering their natural development as a strategy for achieving an effective preventive HIV vaccine. We previously described the developmental process of CH103, a CD4-binding site (CD4bs)-specific monoclonal antibody, and the associated evolution of HIV Envelopes (Envs) within the person (CH505) from whom it was isolated. A series of monomeric gp120 protein subunit immunogens representing the transmitted founder (TF) and Envs that evolved during infection and optimally reacted with lineage members at each step of the CH103 clone maturation path were evaluated in this placebo controlled randomized vaccine trial to test for the first time in humans the concept of whether sequential immunization with gp120 monomeric proteins can recapitulate the development of CD4bs B-cell clonal lineages, including CH103. Methods: HIV Vaccine Trials Network 115 (HVTN 115) was a randomized placebo-controlled vaccine trial at US clinical research sites. We tested the safety and immunogenicity of CH505TF gp120 + GLA-SE (Part A), and then the ability of sequential CH505 gp120 proteins (corresponding to CH505s weeks 53 and 78 Envs) + GLA-SE immunizations to induce CD4bs-specific neutralizing antibodies (Part B). We assessed binding and neutralizing antibody responses, antibody dependent cellular cytotoxicity, antibody dependent cellular phagocytosis, T-cell responses and B-cell phenotyping. Results: We enrolled 42 participants between October 2017 and May 2018 for Part A, and 65 participants from December 2020 to October 2022 for Part B. Immunization with the CH505 gp120 proteins adjuvanted with GLA-SE was well tolerated and induced CD4bs-specific B cells and Env-specific plasma antibodies. The plasma neutralizing antibody response was limited to primarily tier 1 autologous and heterologous HIV-1 strains. Blood-derived B-cell repertoire analyses identified CD4bs antibodies that preferentially bound to open-occluded trimeric Envs that exist in an intermediate state between prefusion-closed to CD4-bound open confirmations, consistent with tier 1 HIV neutralizing activity. Conclusions: Together, these results suggest that the low-affinity CH505TF gp120 monomer elicited CD4bs antibodies in the sera and B-cell repertoires of humans. However, our findings also indicate that gp120 monomers are insufficient to induce detectable bnAb precursors to epitopes on native Env trimers. Nonetheless, our data provide a benchmark for comparison with ongoing clinical trials testing high-affinity CH505 Env trimers for induction of CD4bs bnAb precursors.

Objective: To identify facility-level characteristics - including care level, ownership type, and funding model - associated with poor HIV treatment outcomes, and quantify their independent contributions after adjustment for patient-level clinical factors. Design: Retrospective cross-sectional analysis using multivariable logistic regression with HC3 cluster-robust standard errors to account for facility-level clustering. Setting: HIV care facilities in the Nigerian national HIV programme, spanning primary health centres, secondary health facilities, and tertiary hospitals. Participants: 27,288 HIV-positive patients enrolled on ART, from a publicly available de-identified Quality of Care dataset. Main outcome measures: Composite poor outcome (poor ART adherence, treatment interruption, or mortality); individual outcomes including poor adherence rate, mortality, ART interruption, and diagnosis-to-ART delay exceeding 90 days. Results: Primary health centres had 15.4% composite poor outcome versus 10.2% at tertiary hospitals. After adjustment for patient age, sex, WHO stage, and CD4 count, primary health centre patients had 95% higher odds of poor outcome (OR=1.95; 95%CI 1.45-2.61; p<0.001). NGO-funded facilities had 24% higher odds (OR=1.24; 95%CI 1.10-1.39; p<0.001) and federally funded facilities 25% higher odds (OR=1.25; 95%CI 1.06-1.48; p=0.008). Female sex was independently protective (OR=0.87; 95%CI 0.79-0.96; p=0.003). Diagnosis-to-ART delays exceeded 90 days in 47.3% of patients, with significant variation by facility level (chi-squared=49.4, p<0.001). Conclusions: Facility level and funding model independently predict HIV treatment outcomes after patient-level adjustment. Primary health centres and NGO/federally funded facilities may require targeted quality improvement support. These findings have direct implications for PEPFAR, the Global Fund, and national HIV programme managers.

Introduction: Viral load (VL) monitoring is the gold standard for antiretroviral therapy (ART) monitoring. Still, due to limited funds and infrastructure, many people living with HIV (PLHIV) in low- and middle-income countries do not receive timely VL testing. We evaluated the clinical performance and end-user acceptability of a prototype interferon gamma-induced protein 10 (IP-10) point-of-care (POC) test as a rule-out triage tool to identify individuals unlikely to have unsuppressed VL in PLHIV in Mozambique. Methods: A mixed-methods study was conducted between November 2023 and November 2024 at two primary healthcare facilities in Maputo Province. We enrolled 1,057 PLHIV on ART from stable and specialized risk clinics. Clinical performance of the IP-10 POC test (index test) was compared against plasma HIV VL (reference test; unsuppressed defined as >1000 copies/mL). Socio-demographic and clinical predictors of false-positive results were identified using multivariable logistic regression. Immediate acceptability was assessed through exit interviews on a subset of 43 PLHIV. Results: Among participants (71.7% female; median age 41.4 years), 12.0% had unsuppressed VL. The IP-10 POC test demonstrated high sensitivity (90.6%) and moderate specificity (35.6%). Specificity was higher in clinics treating stable patients (44.5% 95%CI: 39.7-49.3) compared to specialized risk clinics (26.5% 95%CI: 21.1-28.9). The proportion of false-positive results was also higher in patients attending specialized risk clinics. Independent predictors of false positivity included enrolment in a one-stop TB/HIV clinic (aOR=2.99 95%CI: 1.09-8.15), cotrimoxazole use (aOR=2.16, 95% CI: 1.13-4.13), and obesity (aOR=3.47 95%CI: 1.74-6.93). Acceptability was high: 70% of participants appreciated the test simplicity and rapid results, and 95.3% expressed interest in future testing. Most patients preferred finger-prick collection over venous draws. Conclusions: The IP-10 POC test is a highly sensitive triage tool, demonstrating superior performance among stable PLHIV enrolled in differentiated service delivery models like six-month multi-month dispensing. While factors associated with co-infections can reduce specificity, the test's high acceptability and potential to reduce confirmatory VL test demand suggests it could serve as a viable triage strategy for optimizing resources particularly in stable care pathways with a lower prevalence of inflammatory comorbidities. This could enable health systems to reallocate intensive monitoring toward higher-risk populations.

People living with HIV (PLWH) are known to maintain a degree of immune deficiency despite efficient antiretroviral therapy and may exhibit diminished responses to vaccines. In this study, we assessed the immune response to SARS-CoV-2 infection and vaccines in two geographically distinct PLWH populations. PLWH and HIV-negative (HIV-) participants were recruited from Qu&bec City (QC), Canada, and Bobo-Dioulasso (BD), Burkina Faso, for two visits at 24-week intervals during the predominance of the Omicron variant, from May 2022 to September 2023. Blood samples were collected at each visit for the detection of antibodies against spike (anti-S) and nucleocapsid (anti-N) proteins of SARS-CoV-2 in platelet-free plasma. A total of 360 participants were enrolled. We detected anti-S antibodies in 99% of participants, indicating that nearly all had prior exposure to the SARS-CoV-2 spike antigen, either through vaccination or prior infection. Anti-S titers showed no difference between PLWH and HIV& participants in each location, while significantly higher titers were observed in participants from QC compared to BD. In contrast, anti-N antibodies, indicative of prior infection, were detected in 39% and 86% of the participants in QC and BD, respectively, suggesting that the virus circulated largely in the latter population. No difference in anti-N levels was observed between PLWH and HIV& participants in BD. However, participants in QC had significantly lower titers compared to HIV participants. Overall, this study shows that PLWH develop robust antibody responses to SARS-CoV-2 vaccination, comparable to those observed in HIV& participants. Significant geographic differences were observed in anti-S titers, irrespective of HIV status, with participants from QC displaying higher titers. In contrast, participants from BD had higher anti-N antibody prevalence and titers, reflecting more SARS-CoV-2 infections in BD than in QC. Finally, analysis of anti-S antibody titers against several circulating variants revealed significantly lower levels in unvaccinated participants and in those vaccinated with monovalent vaccines in BD. No significant difference was observed between monovalent and bivalent vaccines administered in QC. All authors have seen and approved the manuscript.

BackgroundUndetectable HIV-specific antibodies in early-treated children with confirmed infection correlate with low viral reservoir and may identify those eligible for future HIV remission strategies. The neonatal immune systems unique characteristics, combined with impairments resulting from exposure to maternal HIV and antiretroviral treatment (ART), may affect antibody responses to HIV. Yet immune competence remains understudied in the context of negative HIV serology. The ANRS-EP59-CLEAC study included 76 children and adolescents with HIV. We measured plasma HIV antibodies by enzyme immunoassay, other analytes by ELISA or multiplex assays, and blood cell phenotypes and functions by flow cytometry. We used Fishers and Mann-Whitneys tests and logistic regression to analyze variables associated with negative HIV serology. Nine participants tested negative for HIV-specific antibodies, eight children and one adolescent. Negative HIV serology occurred exclusively in participants who had initiated ART early and had HIV RNA < 50 copies/mL at evaluation. Among 17 early-treated children with sustained viral suppression, only 7 had negative HIV serology. In this subgroup, negative HIV serology associated with higher nadir CD4 counts, lower plasma IgM levels, higher frequencies of circulating follicular CD8 T lymphocytes, and higher expression of the costimulatory molecule CD86 on myeloid dendritic cells. We found no evidence of B or T lymphocyte deficits associated with negative HIV serology. Low antigenic exposure was necessary but insufficient to explain negative HIV serology. Beyond its association with low HIV reservoir, negative HIV serology correlated with less severe prior CD4 T-lymphocyte depletion and higher frequencies of follicular CD8 T lymphocytes. SummaryIn HIV-infected infants, starting antiretroviral therapy (ART) very early dramatically improves health outcomes. An important phenomenon observed in some of these children is that, despite being HIV-infected, they show no detectable antibodies against the virus -- a profile referred to as negative HIV serology. This feature could help identify patients most likely to benefit from future strategies aimed at achieving long-term virus control without treatment. To better understand this phenomenon, we studied HIV-infected children and adolescents enrolled in the ANRS-EP59-CLEAC trial, which compares the effects of ART initiated early (before 6 months of age) versus late (after 24 months). We showed that negative HIV serology is associated with early treatment, but also with a better-preserved immune system: less depletion of CD4 T cells, which are critical immune cells, and a higher abundance of specific T lymphocytes with potent antiviral activity. Importantly, we found no evidence of defects in the mechanisms responsible for antibody production. These findings suggest that negative HIV serology reflects a favorable immunological profile and could serve as a useful marker to select children as candidates for HIV remission trials.

Background: Prostate cancer survival varies by stage at diagnosis, and Black men experience a disproportionate burden of advanced disease. We examined whether neighborhood deprivation, measured by Area Deprivation Index (ADI), contributes to racial differences in metastatic presentation. Methods: We conducted a population-based study of men diagnosed with prostate cancer in the Ohio Cancer Incidence Surveillance System from 1996 to 2016. The primary endpoint was distant-stage disease at diagnosis. Generalized additive models assessed nonlinear associations of ADI and diagnosis year with metastatic risk. Inverse probability of treatment weighting (IPTW) models estimated odds ratios comparing Black with White men after sequential adjustment for diagnosis year, age, insurance, and ADI. Results: Among 135,095 men, 18,690 were Black and 116,405 were White. Distant-stage disease occurred in 7.0% of Black men and 5.0% of White men. Black men had higher median ADI (60.9 vs. 47.3). Medicaid-insured men had the highest unadjusted odds of metastatic presentation (OR, 4.68; 95% CI, 4.13-5.31), exceeding uninsured men (OR, 2.91; 95% CI, 2.54-3.34). In IPTW models without age adjustment, the odds ratio decreased from 1.54 to 1.24 after adding insurance and ADI. In age-adjusted IPTW models, the odds ratio decreased from 1.79 to 1.41 after adding insurance and ADI. Generalized additive models showed increasing metastatic risk at higher ADI values and after 2008. Conclusions: Neighborhood deprivation and insurance-related access explained part, but not all, of the excess odds of metastatic diagnosis among Black men. Impact: Integrating ADI into cancer surveillance may improve identification of populations at risk for late-stage diagnosis.

Understanding HIV transmission in densely populated urban settings is essential to mitigate ongoing epidemic spread. We present a comprehensive analysis of recent HIV transmission dynamics in Greater Mexico City, one of the worlds largest metropolitan areas comprising Mexico City and neighbouring municipalities of the State of Mexico. Drawing from over 7,000 complete pol gene sequences representing around 50% of new cases reported between 2019 and 2022 within the study region, we reconstructed the transmission network based on pairwise genetic distance. We identified ten large transmission clusters exhibiting sustained growth up to the most recent sampling period. We further analysed paired genetic and high- resolution human mobility data using an integrated phylogeographic approach. We observed a heterogeneous pattern of viral spread across the region, supported by an extensive mixing at a wider geographic scale. Across Greater Mexico City, displaying a high population density, HIV transmission is minimally spatially constrained, a pattern likely fuelled by intense human mobility. Thus, population movement weakens isolation by distance in large urban areas even for a chronic infection that is sexually and vertically transmitted. We demonstrate the value of integrating large-scale genetic, epidemiological, and mobility data to resolve contemporary HIV transmission dynamics in densely populated urban settings

BackgroundLarge-scale estimates of animal-to-human drug translation and the study characteristics associated with successful translation remain limited. The expanding preclinical literature also challenges manual evidence synthesis. We developed a natural language processing (NLP) pipeline to structure and link preclinical and clinical evidence at scale. MethodsIn this retrospective meta-research study, we analysed more than 500,000 neuroscience-related animal drug studies from PubMed and linked them to clinical trial and regulatory approval data. NLP methods extracted drug, disease, and experimental design characteristics from abstracts and full texts. Translation was defined as progression to completed phase III/IV trials or regulatory approval. Logistic regression assessed associations between preclinical study characteristics and successful translation. FindingsAmong 291,624 drug entities identified in animal studies, 6{middle dot}7% entered clinical development and 3{middle dot}1% reached phase III/IV trials or regulatory approval. At the drug-disease level, 4{middle dot}4% entered clinical development and 1{middle dot}9% achieved translation. Restricting analyses to successfully linked ontology entities increased estimates to 11{middle dot}3% and 4{middle dot}1%, respectively. Male-only animal studies predominated, whereas reporting of randomisation, blinding, and sample size calculations remained limited. Testing across multiple species and reporting blinding were associated with higher odds of successful translation. InterpretationOnly a minority of interventions tested in animals progress to advanced clinical development or regulatory approval. Greater species diversity and blinding were associated with improved translational success. NLP-based evidence synthesis may support scalable evaluation of translational research and identification of potentially modifiable research practices. FundingSwiss National Science Foundation, UZH Digital Entrepreneurship Fellowship, Universities Federation for Animal Welfare. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched the literature for studies quantifying large-scale animal-to-human translation and factors associated with successful translation. Existing work was mainly limited to specific diseases, interventions, or manually curated datasets, and large-scale linkage of animal and clinical evidence remained limited. Added value of this studyWe developed a natural language processing pipeline linking more than 500,000 animal studies to clinical trial and regulatory approval data. The study provides large-scale estimates of translation and identifies experimental characteristics associated with successful translation. Implications of all the available evidenceThe findings suggest that only a minority of interventions tested in animals progress to advanced clinical development or regulatory approval. Greater species diversity and reporting of blinding were associated with improved translation. Automated evidence synthesis may support more systematic evaluation of translational research practices.