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Journal of the International AIDS Society

○ Wiley

Preprints posted in the last 90 days, ranked by how well they match Journal of the International AIDS Society's content profile, based on 21 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.

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Clinical outcomes of HIV treatment clients enrolled in six-month dispensing after less than 6 months on treatment in Zambia: A target trial emulation

KACHINGWE, E.; Fox, M. P.; Ntjikelane, V.; Mokhele, I.; Shumba, K.; Rosen, S.; Kamanga, A.; Haimbe, P.; Sivile, S.; Huber, A. N.

2026-08-02 hiv aids 10.64898/2026.07.30.26358576 medRxiv
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Background: Six-month multi-month dispensing (6MMD) of antiretroviral therapy (ART) reduces clinic visit frequency and is associated with improved retention in care. During the COVID-19 pandemic, Zambia offered 6MMD to clients 3 months after ART initiation, rather than 6 months standard requirement. We estimated the effect of early (3<6 months on ART) versus standard (6-12 months) 6MMD enrolment on the rate of treatment interruption. Methods: We emulated a target trial using routinely collected electronic medical records from 12 public health facilities in Zambia. Eligible clients were 15 years and above, initiated ART 01/20-08/22, were WHO stage 1 or 2 at ART initiation, and had more than 21 months of potential follow-up. Treatment interruption was defined as missing a scheduled clinic or pharmacy visit by more than 28 days. We applied a clone-censor-weight approach to reduce immortal time bias. Clones were censored when observed dispensing deviated from their assigned strategy. Inverse probability of censoring weights (IPCW) accounted for informative censoring, while inverse probability of treatment weights (IPTW) balanced measured baseline confounders between strategies. We used weighted pooled logistic regression of person-month data to estimate the odds of treatment interruption between early and standard 6MMD enrollers, including follow-up months to model the monthly baseline risk. Results: A total of 6,142 ART clients met the inclusion criteria. 741 (12.1%) were early 6MMD enrollers, 1,590 (26.1%) standard 6MMD enrollers, and 3,811 (62.0%) eligible clients who never enrolled in 6MMD. During follow-up, 268 treatment interruptions occurred. In the primary analysis, early 6MMD was associated with lower odds of treatment interruption than standard 6MMD OR 0.701 (95% CI 0.51-0.97). The predicted cumulative probability of treatment interruption at 18 months was 6.5% under the early 6MMD strategy and 9.1% under the standard strategy (risk difference: -2.6 percentage points). Conclusions: Enrolment in 6MMD at 3-6 months after ART initiation was associated with lower odds of treatment interruption than standard enrolment at 6-12 months, with a predicted absolute risk difference of -2.6 percentage points at 18 months. We found no evidence that earlier access to 6MMD increases the risk of treatment interruption.

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Retention in paediatric and adolescent HIV care among ART initiation cohorts in Uganda, 2020-2023

Aman, K. D.; Migisha, R.; Lukabwe, I.; Matovu, N.; Nuwamanya, A.; Kigongo, V. J.; Wobusobozi, J.; Nakaweesi, W.; Alupo, A. L.; Namwabira, A.; Nalubega, F.; Bulage, L.; Kwesiga, B.; Ario, A. R.; Namusoke Magongo, E.

2026-10-02 hiv aids 10.64898/2026.10.01.26364483 medRxiv
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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.

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Discordance Between Biomarker-Confirmed Antiretroviral Therapy and Self-Reported HIV Status Among People Living with HIV in Zambia and South Africa: A Secondary Analysis of HPTN 071 (PopART)

Nakalega, R.; Haines, D.; Hayes, R. J.; Eshleman, S. H.; Ayles, H.; Bock, P.; Floyd, S.; Fidler, S.; Clarke, W.; Agyei, Y.; Breaud, A.; Mirembe, B. G.; Nakabiito, C.; Donnell, D.

2026-07-27 hiv aids 10.64898/2026.07.22.26358720 medRxiv
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Background: Misclassification of HIV status in population-based surveys remains a critical barrier to accurate surveillance and program evaluation. Self-reported HIV status may diverge from objective measures, particularly among individuals receiving antiretroviral therapy (ART). We used biomarker-confirmed antiretroviral (ARV) drug detection to assess the prevalence and correlates of discordance between self-reported HIV status and biologic evidence of HIV treatment among people living with HIV (PLHIV) in Zambia and South Africa. Methods: We conducted a secondary analysis of the HPTN 071 (PopART) cluster-randomized trial. At the 24-month survey visit, participants underwent HIV testing and laboratory assessment for ARV drugs in plasma. We defined discordant self-report (hereafter "non-disclosure") as reporting HIV-negative or unknown status among individuals with ARV drugs detected. We estimated the prevalence of non-disclosure, compared prevalence by study arm, and used modified Poisson regression to identify associated factors. We also examined whether non-disclosure was associated with viral suppression (<400 copies/mL). Results: Among 3,240 PLHIV with ARV drugs detected, 552 (17.0%) did not report an HIV-positive status--indicating that nearly one in six individuals on ART were misclassified by self-report. Non-disclosure did not differ between intervention and control arms (adjusted relative risk [aRR]: 1.03; 95% CI: 0.67-1.58). Non-disclosure was more common among younger individuals (age 18-24 years: aRR 2.30; 95% CI: 1.66-3.19), men (aRR: 1.39; 95% CI: 1.07-1.79), and those in formal employment (aRR: 1.42; 95% CI: 1.06-1.90). Individuals reporting condomless sex at last encounter were also more likely not to disclose (aRR: 1.59; 95% CI: 1.31-1.92). Viral suppression was high overall (93.7%) and did not differ by disclosure status (aRR: 1.06; 95% CI: 0.74-1.52). Conclusion: A substantial proportion of PLHIV receiving ART did not report a known HIV-positive status, highlighting important discordance between biomarker evidence and self-reported data. Despite high levels of viral suppression, these individuals remain "hidden" from routine surveillance, with implications for estimating HIV diagnosis and treatment coverage. Strategies that incorporate objective measures alongside self-report, and that address social and structural barriers to disclosure, are essential to improve the accuracy of HIV surveillance and guide effective public health responses.

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The association between HIV treatment interruptions and viral suppression during the early treatment period: retrospective cohort study in South Africa

Benade, M.; Maskew, M.; Mutanda, N.; Scott, N.; Morgan, A.; Ntjikelane, V.; Sande, L.; Malala, L.; Manganye, M.; Nichols, B.; Rosen, S.

2026-08-23 hiv aids 10.64898/2026.08.20.26360935 medRxiv
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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.

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Engaging Zimbabwean men and stakeholders in the co-adaptation of peer-delivered HIV self-testing: iterative prototyping of the IMPERATIVE Trial

McGowan, M.; Maswera, R.; Chisvo, L.; Moorhouse, L.; Dzamatira, F.; Mandizvidza, P.; Tsenesa, B.; Otambo, W.; Inghels, M.; Harling, G.; Mee, P.; Baernighausen, T.; Gregson, S.; Nyamukapa, C.; Tanser, F.; Skovdal, M.

2026-08-11 hiv aids 10.64898/2026.08.10.26360082 medRxiv
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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.

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Readiness to start long acting injectable HIV treatment and prevention and conditions for acceptance among clinic clients in Uganda

Olet, S. C.; Muluga, W. U.; Musoki, D.; Kihumuro, B. R.; Muluga, F.; Ssebandeke, I.; Among, F.; Stecher, C. D.; Musoke, D.

2026-10-15 hiv aids 10.64898/2026.10.14.26365499 medRxiv
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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.

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Depressive symptoms and viral load suppression among adolescents and youth living with HIV in Malawi: a cross-sectional analysis of MPHIA 2020-2021

Ndhlovu, G.; de Voux, A.

2026-10-06 hiv aids 10.64898/2026.10.05.26364733 medRxiv
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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.

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Mechanisms of action of a community-led HIV prevention and treatment programme for female sex workers in Zimbabwe: a mixed-method analysis

Busza, J.; Jones, H.; Matambanadzo, P.; Hove, T.; Chabata, S.; Kujeke, T.; Makamba, M.; Madimutsa, G.; Machingura, F.; Cowan, F.; Hargreaves, J.

2026-10-16 hiv aids 10.64898/2026.10.08.26365041 medRxiv
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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.

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Service disruptions and stockouts: Ongoing impacts of U.S. funding freezes on HIV care across clinics in 38 low- and middle-income countries in late 2025

Brazier, E.; Kludze, M.; Maruri, F.; Niyongabo, A.; Kreniske, P.; Duda, S. N.; Nash, D.

2026-08-06 hiv aids 10.64898/2026.08.04.26359701 medRxiv
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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.

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Increased HIV incidence during Event-Driven PrEP compared to Daily PrEP in the Netherlands

Willemstein, I. J. M.; Prins, M.; Heijne, J. C. M.; Davidovich, U.; Schim van der Loeff, M. F.; Chaname Pinedo, L.; Akwiwu, E. U.; van Benthem, B.; Hoornenborg, E.; Jongen, V. W.

2026-08-13 epidemiology 10.64898/2026.08.12.26360235 medRxiv
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Background Clinical trials demonstrated high efficacy of daily and event-driven oral pre-exposure prophylaxis (PrEP) in HIV prevention. Event-driven PrEP involves taking two tablets before and two times one tablet after sexual contact (2-1-1/on-demand). While both are implemented in Dutch clinical practice, evaluating real-world effectiveness requires large-scale data from routine clinical care. This study compared HIV incidence between daily and event-driven PrEP in the Netherlands. Methods We used surveillance data from the Dutch national PrEP program (August 1, 2019-December 31, 2025). Individuals [&ge;]16 years with [&ge;]1 follow-up consultation after PrEP initiation were included; PrEP regimen since last visit was recorded at each visit. Person-time was modeled as time-varying based on the regimen reported at each consultation. HIV incidence rates were calculated per 100 person-years and Cox proportional hazards models estimated hazard ratios between regimens for HIV acquisition, adjusted for sociodemographics, sexual behavior, and history of sexually transmissible infections. Findings 16,469 individuals (15,843 men who have sex with men, 579 transgender and gender diverse persons, 45 women and two men who have sex with women) initiated PrEP and had [&ge;]1 follow-up visit (median follow-up 2.0 years (IQR=0.8-4.0)). Median age was 33 years (IQR=27-44). 49 PrEP users were diagnosed with HIV over 41,092 person-years (IR=0.12/100 py;95%CI=0.09-0.16), of whom 42 event-driven users (IR=0.20/100 py;95%CI=0.15-0.27) and seven daily PrEP users (IR=0.04/100 py;95%CI=0.02-0.07). In multivariable Cox regression, event-driven PrEP use was associated with a higher hazard of HIV acquisition (aHR=7.0;95%CI=3.0-16.4). Interpretation Despite overall low HIV incidence, the incidence rate in the Dutch national PrEP program was seven-fold higher during event-driven PrEP use compared to daily, which may be due to lower adherence. These findings denotes that, in real-world settings, improved person-centered counseling is needed for individuals interested in, or using event-driven PrEP. Research should identify domains and preferred methods of support. Funding None for this study.

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Diagnostic accuracy of point-of-care urine tenofovir test, and associations between metrics of tenofovir use and treatment outcomes in a community ART programme

Naidu, L.; Tlhaku, K.; Govender, K.; Sookrajh, Y.; Moodley, P.; van der Molen, J.; Samsunder, N.; Lewis, L.; Gandhi, M.; Drain, P. K.; Butler, C. C.; Hayward, G.; Garrett, N.; Dorward, J.

2026-08-14 hiv aids 10.64898/2026.08.13.26360358 medRxiv
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Background Urine tenofovir (uTFV) and dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations respectively estimate short- and medium-term adherence to tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART). We evaluated the accuracy of a point-of-care uTFV assay, and associations between uTFV/TFV-DP, and viral load (VL) and retention outcomes within a South African community ART programme. Methods We measured uTFV and DBS TFV-DP concentrations using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We calculated sensitivity and specificity of the point-of-care uTFV assay at the manufacturer-recommended threshold of [&ge;]1,500 ng/mL compared to LC-MS/MS. We assessed associations of the point-of-care uTFV assay, and DBS TFV-DP concentrations with concurrent viraemia, and with retention-in-care by 16 weeks post-enrolment. Results Of 196 adults median age was 44 years, 127 (64.8%) were female, and 191 (97.4%) were receiving TDF. 185 (94.4%) had detectable point-of-care uTFV, which had high sensitivity (99.5%, 95% CI 96.5-100%) and moderate specificity (76.9%, 95% CI 46.0-93.8%) for detecting uTFV [&ge;]1,500 ng/mL. Two participants had concurrent viraemia [&ge;]1,000 copies/mL; of these 50.0% (95% CI 9.4-90.5) had undetectable point-of-care uTFV, and 100% (95% CI 19.7-100) had low TFV-DP <483 fmol/punch. Among participants without viraemia 97.4% (95% CI 93.6-99.0) had detectable uTFV, and 98.1% (95.3-99.6) had high TFV-DP [&ge;]483 fmol/punch. Point-of-care uTFV and DBS TFV-DP were not associated with retention-in-care. Conclusions The point-of-care uTFV assay demonstrated high sensitivity and moderate specificity to detect uTFV. Over 95% of people without viraemia had detectable point-of-care uTFV or high DBS TFV-DP levels respectively, but these were not associated with 16-week retention-in-care.

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Facility-level variation in HIV service delivery volumes before and after the 2025 PEPFAR funding cuts: a retrospective analysis of District Health Information System data in Zambia

Mwale, M.; Rosen, S.; Ngoma, T.; Sivile, S.; Sianyinda, C.; Haimbe, P.; Shakwelele, H.; Benade, M.; Morgan, A.; Marri, A.; Huber, A.; Mokhele, I.

2026-09-29 hiv aids 10.64898/2026.09.27.26364124 medRxiv
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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.

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Time to PrEP Disengagement and Associated Factors Among Adolescents and Young Adults from Key and Priority Populations in Uganda. A survival Analysis

Mwima, S.; Walwo, S.

2026-07-24 hiv aids 10.64898/2026.07.22.26358724 medRxiv
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Background Adolescents and young adults (AYAs) from key and priority populations face persistent challenges with sustained engagement in HIV pre-exposure prophylaxis (PrEP) care. While PrEP initiation has expanded across sub-Saharan Africa, evidence on long-term retention and determinants of disengagement among AYAs remains limited. We examined time to PrEP disengagement and associated factors among AYAs initiating PrEP in eastern Uganda. Methods We conducted a retrospective longitudinal analysis of routinely collected program data for AYAs aged 15-29 years from key and priority populations who initiated PrEP between 2019 and 2025 at Mbale Regional Referral Hospital. Time to PrEP disengagement was assessed using Kaplan-Meier survival analysis and Cox proportional hazards regression. Multivariable models adjusted for sociodemographic, relational, behavioral, and service delivery factors. Sensitivity analyses redefined the time origin to day 91 following PrEP initiation to reflect the programmatic 90-day grace period. Results Among 3,553 AYAs initiating PrEP, the median time to disengagement was 284 days (95% CI: 273-295). The median age was 24 years (interquartile range [IQR]: 20-26). The probability of remaining engaged in PrEP care declined from 60.1% at 90 days to 20.2% at 365 days. Survival patterns differed significantly by population category and sex at birth but not by age group. In adjusted analyses (N = 3,391), knowledge of a partners HIV status (aHR = 2.04; 95% CI: 1.82-2.29) and initiation through community-based services (aHR = 1.42; 95% CI: 1.17-1.72) were associated with faster disengagement. Married participants had lower hazards of disengagement compared with single participants (aHR = 0.69; 95% CI: 0.64-0.76). Reporting an STI syndrome (aHR = 0.42; 95% CI: 0.32-0.55) or recent gender-based violence (aHR = 0.76; 95% CI: 0.60-0.96) was associated with reduced disengagement. Findings were highly consistent in sensitivity analyses using an alternative risk-period definition. Conclusions PrEP disengagement among AYAs occurs rapidly following initiation, with substantial attrition within the first year. Relational factors, service delivery modality, and population-specific vulnerabilities strongly shape retention trajectories. These findings underscore the need for risk-responsive, differentiated PrEP delivery strategies that strengthen partner-based services, integrate STI and GBV screening, and adapt retention support for AYAs in community and facility settings.

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Socio-demographic and behavioral factors influencing the utilization of community-post interventions for HIV testing services by men (>=18 years) in Kericho County, Kenya

Kongani, L.; Nyaberi, J. M.; Ngure, K.

2026-09-08 hiv aids 10.64898/2026.09.03.26362133 medRxiv
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Men continue to test for HIV less often than women in many settings, including Kenya. Community-based HIV testing may reduce access barriers, but evidence on factors associated with mens use of community-post services remains limited. This analytical cross-sectional mixed-methods study examined socio-demographic and behavioral factors associated with use of community posts for HIV testing among adult men in Kericho County, Kenya. Quantitative data were collected using self-administered questionnaires at two community posts and two facility-based Comprehensive Care Centres. The Kobo export contained 438 questionnaire records; 41 pretest records were excluded in line with the study protocol, leaving 397 records for analysis. Community-post use in the preceding year was reported by 208 of 396 respondents with complete outcome data (52.5%). In adjusted analysis, community-post use was higher among employed men (AOR 2.94, 95% CI 1.48-5.82; p=0.002) and men engaged in business (AOR 2.56, 95% CI 1.15-5.69; p=0.021) than among unemployed/other men. Age, marital status, religion, education and monthly income were not independently associated with community-post use. In the behavioral model, respondents who were unwilling or unsure about participating in future community HIV-testing campaigns had lower odds of community-post use (AOR 0.20, 95% CI 0.10-0.39; p<0.001). Frequent travel or migration (AOR 0.19, 95% CI 0.06-0.65; p=0.008) and unprotected sex (AOR 0.54, 95% CI 0.34-0.87; p=0.012) were also associated with lower odds of community-post use after adjustment. These findings identify occupational and selected behavioral factors associated with community-post use among the men studied; the cross-sectional design does not establish causality.

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Impact of a novel mental health chatbot on depression knowledge among youth with HIV: A pilot study

Galea, J. T.; Contreras, C.; Vazquez, D.; Rupani, N.; Greene, K. Y.; Tapia, M.; Kolevic, L.; Kosyluk, K.; Franke, M. F.

2026-07-29 hiv aids 10.64898/2026.07.25.26358927 medRxiv
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Introduction: Adolescents living with HIV (ALWH) face disproportionately high rates of depression and anxiety, which can negatively affect antiretroviral adherence, viral suppression, and overall health outcomes. Despite the close relationship between mental wellness and HIV care, mental health services remain inadequately integrated into HIV programs, particularly in low- and middle-income countries. To address this gap, we developed EVA (Educaci&oacuten, Vinculaci&oacuten y Autoayuda), a mental health chatbot co-designed with ALWH to provide psychoeducation on depression and anxiety, teach self-help skills, and facilitate linkage to mental health resources. We evaluated EVA's preliminary impact on depression knowledge and its feasibility and acceptability among ALWH in Lima, Peru. Methods: During January - August 2024, ALWH in Lima, Peru completed baseline assessments, engaged independently with EVA for 20 minutes, and completed endline measures. The primary outcome was change in depression knowledge measured using the Adolescent Depression Knowledge Questionnaire (ADKQ). Secondary outcomes included acceptability, appropriateness, feasibility, intention to use and recommend the chatbot, and satisfaction with the chatbot's features and content. Paired-samples t- tests were used to evaluate pre-post changes in depression knowledge. Results: Fifty ALWH aged 11 - 19 years participated, among whom 70% reported greater-than-minimal depressive symptoms, 60% greater-than-minimal anxiety symptoms, and 92% moderate or high perceived stress. Following a single interaction with EVA, depression knowledge increased significantly, from a mean ADKQ score of 6.88 (SD=1.85) to 8.12 (SD=2.20), t(49) = -5.03, p<.001, representing a large effect size (d=1.74). The chatbot was rated highly for acceptability, appropriateness, and feasibility, and participants reported strong intentions to use and recommend it, as well as high satisfaction with its educational content, usability, and self-help resources. Conclusions: A brief interaction with a mental health chatbot developed with and for ALWH in Peru significantly increased depression knowledge and was rated highly acceptable and feasible. Mental health chatbots may offer a low-cost, scalable approach to support mental health education and linkage to care within adolescent HIV services. Future longitudinal studies should assess sustained impact on mental health outcomes and help-seeking behavior; however, the benefits of chatbots should be weighed against their potential mental health risks.

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Relative fertility of HIV-positive women in the ART era: updated estimates from national household survey data

Imai-Eaton, J. W. W.; Glaubius, R.; Mahy, M.; Johnson, L. F.; Stover, J.; Marston, M.

2026-08-12 epidemiology 10.64898/2026.08.11.26360197 medRxiv
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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.

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Dynamic Prediction to Predict Virologic Failure in Antiretroviral Treated People Living with HIV: Cohort Analysis of Routine Electronic Health Records Data in the Western Cape, South Africa

Honwana, F.; Mukonda, E.; Gumedze, F.; Hsiao, N.-y.; Myer, L.; Lesosky, M.

2026-09-11 hiv aids 10.64898/2026.09.08.26362496 medRxiv
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Objectives Virologic failure (VF) remains a major challenge in HIV care, particularly in resource-limited settings where timely identification is critical. Dynamic prediction models can provide continuously updated, individual-level risk estimates using longitudinal biomarker data. However, their applicability to routinely collected electronic health record (EHR) data remains poorly understood. We developed and internally validated a dynamic prediction model for VF using routine EHR data from people with HIV (PWH) receiving antiretroviral therapy in South Africa. Methods A joint model (JM) linking a linear mixed-effects model for longitudinal HIV viral load (HIVVL) to a Cox model for time to first VF, adjusted for baseline age group and sex at birth, was developed using routine National Health Laboratory Service data from 122,425 PWH in the Western Cape, South Africa (SA) (January 2008-September 2018), randomly split into development (n = 91,818; 75%) and validation (n = 30,607; 25%) cohorts. Predictive performance was evaluated using time-dependent area under the receiver operating characteristic curve (AUC) and Brier scores at 12 and 24 months. Results Overall, 12,547 PWH (10.2%) experienced VF. The current value-parameterized model was used and showed moderate discrimination (AUC: 0.69 and 0.73) and good calibration (Brier scores: 0.033 and 0.051) at 12 and 24 months. Dynamic predictions updated meaningfully at each visit, demonstrating potential to flag individuals at elevated VF risk for timely clinical intervention. Conclusions Dynamic prediction models hold genuine promises to support personalized, timely clinical decision-making for PWH. However, EHR data with sparse measurements, missing clinical covariates, and irregular follow-up limit discriminative performance despite adequate calibration, demonstrating that data quality and covariate availability are at least as consequential as modelling strategy in real-world prediction settings.

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'We need this now': Acceptability and usability of a pediatric antiretroviral microarray patch prototype in South Africa and Uganda

Quintanar-Solares, M.; Tumusiime, J. K.; Mbotho, P.; Ngcobo, N.; Kwarteng, P.; Sibaya, T.; Mistilis, J. J.; Archary, M.; Choy, R. K. M.

2026-09-23 hiv aids 10.64898/2026.09.17.26363333 medRxiv
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Children living with HIV face significant challenges with adherence to daily oral antiretroviral (ARV) treatment due to poor palatability, complicated dosing, and caregiver burden. Long-acting delivery systems designed specifically for children may help overcome these barriers. Microarray patches, also known as microneedle patches, are a needle-free drug delivery technology that could simplify treatment administration and improve adherence. This study explored the acceptability and usability of a pediatric ARV microarray patch prototype among stakeholders in South Africa and Uganda, two countries with a high burden of pediatric HIV. A formative study was conducted in 2024 with 48 participants, including caregivers, community health workers, health care providers, and decision-makers. Data were collected through qualitative methods: interviews, simulated use sessions, and observations. Participants demonstrated high usability of the prototype, with 97% completing all application steps and nearly all reporting the prototype as easy to use and expressing confidence in successful administration. Most participants found the prototypes size, wear time, and temporary skin changes acceptable, and all preferred a weekly patch over daily oral treatment. Applying multiple patches at once to achieve a therapeutic dose was considered feasible. Decision-makers foresaw strong programmatic fit of a pediatric ARV microarray patch if caregivers apply the patch at home following initial facility-based guidance. Overall, the pediatric ARV microarray patch prototype was perceived as highly acceptable and usable across diverse end users, findings that generally align with studies of microarray patches for other use cases (e.g., contraception, HIV pre-exposure prophylaxis, vaccine delivery). The simplicity, comfort, and convenience of a pediatric ARV microarray patch could substantially improve treatment adherence and quality of life for children living with HIV. Further development and clinical evaluation are warranted to advance this promising technology toward real-world use.

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Characteristics of HIV cure-related clinical trials affecting study participation: A choice-based conjoint analysis experiment

Galea, J. T.; Junker, A.; Greene, K. Y.; Polonijo, A.; Dube, K.; Taylor, J.; Christenson, C.; Brown, B.

2026-10-05 hiv aids 10.64898/2026.10.03.26364635 medRxiv
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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.

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Internalized HIV stigma, antiretroviral therapy adherence, and health-related quality of life among women living with HIV in Nigeria

Raji, D. O.; Akinsolu, F. T.; Ezechi, L. O.; Abodunrin, O. R.; Gbaja-biamila, T. A.; Musari-Martin, T.; Oba, A. C.; Blessing, L. A.; Olatunji, I. A.; Adelaja, G. M.; Brai, J. N.; Aduroja, P. E.; Oredein, A. O.; Wiley, Z.; Ezechi, O. C.

2026-09-30 hiv aids 10.64898/2026.09.28.26364230 medRxiv
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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.