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JAIDS Journal of Acquired Immune Deficiency Syndromes

Ovid Technologies (Wolters Kluwer Health)

Preprints posted in the last 90 days, ranked by how well they match JAIDS Journal of Acquired Immune Deficiency Syndromes's content profile, based on 19 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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Comparative evaluation of HIV testing interventions for men who have sex with men in the Netherlands: insights for a low-incidence setting

Teslya, A.; Roberts, J. A.; Heijne, J. C. M.; Schim van der Loeff, M. F.; van Sighem, A.; Schmidt, A. J.; Jonas, K.; Kretzschmar, M. E.; Rozhnova, G.

2026-03-17 hiv aids 10.64898/2026.03.16.26348499 medRxiv
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BackgroundAlthough the number of new HIV diagnoses among men who have sex with men (MSM) in the Netherlands has declined considerably, the recent plateau suggests ongoing transmission. In 2024, 29% of new diagnoses among MSM were in a late HIV stage, showing that the time between infection and diagnosis can still be substantially reduced. In low-incidence settings, infections introduced through immigration are increasingly important in sustaining transmission, highlighting the need to re-evaluate current testing guidelines. We assess targeted testing strategies among MSM in the Netherlands addressing these considerations. MethodsWe used an agent-based model of HIV transmission among MSM in the Netherlands, incorporating infections acquired domestically and abroad. For 2024 - 2040, we simulated testing interventions targeting different subgroups, including offering an HIV test to immigrants upon entry, increasing testing rates among MSM residing in the Netherlands, and combinations of these approaches. ResultsOffering HIV testing to immigrating MSM at the entry averted up to 94 (95-th % quantile interval, 95% QI -128 - 328) new infections over 15 years if at least 50% take the test. Increasing testing to every 7 months in the general MSM population achieved the largest reduction, with up to 508 (95% QI 292 - 900) infections averted. The same testing rate in MSM with more than 5 partners within the previous six months resulted in 340 (95% QI 132-592) infections averted. Combining testing at entry with 7-months testing among general resident MSM averted the most infections, 534 (95% QI 308 - 884). ConclusionsCombination of offering HIV test to immigrating MSM at the entry with 7-month testing frequency in the general resident MSM population can substantially reduce HIV infections. The difference in impact between targeting general MSM and those with relatively high recent partner numbers suggests that criteria for being at risk of having HIV need to expand. 1 Author summaryWhile HIV transmission among MSM in the Netherlands has decreased substantially over the last decade, it is still ongoing. In 2024, 29% of new HIV diagnoses in MSM were in individuals in late-stage of HIV infection, suggesting that the time between HIV acquisition and diagnosis should be shortened further. Additionally, in a low-incidence setting such as MSM in the Netherlands, introduction of HIV infections through immigration becomes more important. We evaluated several HIV testing strategies for this context, considering both immigrating MSM and resident MSM. While offering HIV test at entry point can avert many HIV infections, increasing testing rate in resident MSM to on average every seven months can avert substantially more HIV infections. The greatest impact is achieved when these approaches are combined: targeting both immigrating MSM and those already living in the country. This combined strategy requires the fewest additional tests per infection averted. Importantly, our simulations show that there are MSM living with undiagnosed HIV who do not necessarily meet the traditional criteria for being at risk. Improved testing strategies can help reach these individuals earlier, benefiting both public and their personal health.

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Exploring provider preferences in the design of HIV treatment packages integrating long-acting injectable antiretroviral therapy in New York Ryan White Part A medical case management programs

Zimba, R.; Kelvin, E. A.; Kulkarni, S.; Carmona, J.; Avoundjian, T.; Emmert, C.; Peterson, M.; Irvine, M.; Nash, D.

2026-04-23 hiv aids 10.64898/2026.04.22.26351494 medRxiv
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Introduction Understanding provider preferences for the design of HIV treatment packages could enhance the implementation of programs to support the adoption of long-acting injectable antiretroviral therapy (LAI ART) by people living with HIV who are interested in initiating this treatment modality. Methods We recruited providers from New York City (NYC), Rockland, Putman, and Westchester County Ryan White Part A Medical Case Management (MCM) programs to complete a discrete choice experiment (DCE) containing twelve tasks with two alternatives and an opt-out option, with additional survey questions about implementation readiness and choice motivations. The alternatives included four attributes--Type of ART Medication (monthly or bimonthly LAI ART), Service Location and Mode, Support for Clients, and Rewards for Clients--with 2-4 levels each. We ran latent class multinomial logit analyses (LCA) with 1-5 classes to estimate preferences and explore hypothesis-free preference heterogeneity. We estimated attribute influence using relative importances and preferences using zero-centered part-worth utilities for each level. Results One hundred seventy-seven providers completed the survey (July 2022-January 2023). About half (52%) were 40-59 years old, 72% identified as women, and the plurality (41%) identified as Latino/a. We chose the two-group LCA solution. Bimonthly LAI ART was preferred over monthly LAI ART overall and in both groups. Group 1 (n=45) preferred more traditional adherence supports (e.g., injections at the clinic by appointment, injection appointment reminders) whereas Group 2 (n=132) preferred more client-centered supports (e.g., injections at home by appointment, free transportation to injection appointments if at a clinic). Both groups preferred higher monetary value gift cards for clients for every on-time injection. The top-ranking motivations indicated that participants prioritized patient convenience over job satisfaction and administrative or financial feasibility for the agency. The scores for all implementation measures indicate readiness to implement LAI ART in both groups. Conclusions Our implementation science-focused study suggests that providers of MCM services in NYC and surrounding counties are motivated to offer services to support clients' access and adherence to LAI ART. More work is needed to understand how programs have, in fact, integrated supports for LAI ART into their services.

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Trends in Healthcare Costs among People Living with HIV in Ontario, Canada, 2003-2018: Results from a Population-Based Retrospective Cohort Study

Xi, M.; Dumicho, A. Y.; Tan, D. H. S.; Masucci, L.; Burchell, A. N.; Zwerling, A.; Ma, H.; Zhang, W.; OHTN Cohort Study Team, ; Mishra, S.; Thavorn, K.

2026-02-19 hiv aids 10.64898/2026.02.18.26346556 medRxiv
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ObjectiveTo quantify trends in annual mean healthcare costs per person living with HIV from 2003 to 2018 from a publicly funded healthcare system perspective. DesignWe conducted a retrospective population-based study using administrative health data in Ontario, Canada, including 25,842 people living with HIV diagnosed and entering care between 1992 and 2018. A nested cohort from the Ontario HIV Treatment Network Cohort Study (n=3,516) provided additional HIV-related characteristics. MethodsAnnual mean healthcare costs per person were estimated using a validated costing algorithm and inflated to 2025 Canadian dollars. Trends were examined overall and stratified by sociodemographic factors (age, sex, rurality, neighbourhood income, immigration status) and year of entry into HIV care. Within the nested cohort, trends were stratified by nadir CD4 count and any antiretroviral therapy use since diagnosis. ResultsAnnual mean cost per person increased from $11,963 in 2003 to $16,721 in 2018. Medication costs remained the largest cost component throughout (47.4-61.7%) and closely mirrored overall trends. Higher annual mean costs were consistently observed among individuals diagnosed at older ages, lower-income neighbourhood residents, long-term Ontario residents (Canadian-born or immigrated before 1985), and individuals with nadir CD4<200cells/{micro}L. ConclusionMedication expenditures continue to drive healthcare costs for people living with HIV. Cost containing strategies, including expanded generic substitution and strengthened price negotiation, may reduce costs without compromising outcomes. Persistent cost disparities highlight the need to address delayed treatment initiation and broader social determinants shaping HIV treatment access and sustained engagement in care.

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Impact of violence on HIV outcomes among female sex workers: A global systematic review and meta-analysis

Dawe, J.; Mazhar, K. A.; Khan, S. A.; Njiro, B. J.; Bendaud, V.; Sabin, K.; Ambia, J.; Trickey, A.; Barrass, L.; Asgharzadeh, A.; Stone, J.; Artenie, A.; Vickerman, P.

2026-02-27 hiv aids 10.64898/2026.02.27.26346881 medRxiv
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BackgroundFemale sex workers (FSW) are a key population for HIV prevention and care. Increasing evidence suggests that social and structural barriers are key drivers of HIV transmission. This global systematic review assesses whether experiencing violence is associated with worse HIV outcomes among FSW. Methods and FindingsWe searched MEDLINE, Embase, and PsycINFO databases for studies published from January 1st, 2010 to February 10th, 2025 assessing the impact of violence on HIV outcomes among FSW, without restriction to language and study design. Some studies had multiple estimates due to reporting on multiple outcomes or exposures of interest. We pooled data from eligible studies using multi-level random-effects meta-analyses to quantify associations between recent (past year) or lifetime exposure to violence (physical, sexual, emotional/psychological and/or financial) and HIV outcomes (prevalent and incident HIV infection, HIV testing, ART use, ART adherence, and viral suppression) among FSW. We preferentially used adjusted estimates over unadjusted estimates if both were available. We included 91 studies with 221 estimates, comprising 179,727 FSWs in 37 countries. We found higher odds of prevalent HIV infection among FSWs with recent (pooled odds ratio (pOR):1.33; 95%CI:1.17-1.51; I2:64%; n=73 estimates) and lifetime (pOR:1.36; 95%CI:1.24-1.49; I2:38%; n=67) experiences of violence. Recently experiencing violence was associated with reduced odds of ART use (pOR:0.78; 95%CI:0.64-0.94; I2:8%; n=17). Lifetime exposure to violence was associated with reduced odds of viral suppression (pOR:0.88; 95%CI:0.79-0.98; I2:20%; n=6). There was no evidence of associations between violence and HIV incidence, HIV testing and ART adherence. ConclusionsExperiencing violence may increase HIV transmission risk and worsen HIV treatment outcomes among FSW. HIV interventions for FSWs must address violence as a structural determinant of HIV.

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Characterizing the impact of the COVID-19 pandemic on HIV testing among Medicaid beneficiaries

Palatino, M.; Rudolph, J. E.; Zhou, Y.; Calkins, K.; Yenokyan, K.; Lucas, G. M.; Xu, X.; Wentz, E.; Joshu, C. E.; Lau, B.

2026-02-14 epidemiology 10.64898/2026.02.12.26346199 medRxiv
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ObjectivesEstimate the HIV testing, diagnoses, and test positivity rates among Medicaid beneficiaries in 2016-2021 and assess the impact of the COVID-19 pandemic on these outcomes. DesignProspective observational study of Medicaid enrollment, inpatient, and outpatient claims data from 27 states, 2016-2021. MethodsWe assessed Medicaid claims from adult beneficiaries with full benefits whose first continuous enrollment was [&ge;]6 months without dual enrollment in other insurance, and without previous HIV diagnosis. We estimated the rates of annual testing, HIV diagnosis, and proportion of positive HIV tests among the tested using Poisson regression models. Bayesian structural time series modelling was performed to examine the pandemics impact on study outcomes with 3/16/2020-12/31/2021 as the pandemic period. We estimated rates overall and by age, sex, race/ethnicity, and states level of COVID-19-related restriction policies. ResultsWe included 20,508,785 beneficiaries. Male beneficiaries, especially 18-34-year-olds, had lower annual testing uptake and higher test positivity rates than female beneficiaries. Black beneficiaries had higher annual testing rates than White and Hispanic beneficiaries. While the pandemic acutely disrupted the increasing pre-pandemic testing trend, the rates recovered to the expected level had the pandemic not happened, except among 18-34-year-old male beneficiaries, whose pandemic rates were, on average, 18.1% lower (95% confidence interval:-22.3,-13.8) than projected rates. HIV diagnosis and test positivity rates were not affected by the pandemic. ConclusionThe pandemic significantly impacted the testing uptake among young male beneficiaries, highlighting the need for innovative strategies to improve HIV testing uptake in this demographic, restoring it to pre-pandemic levels or better.

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Projected Aging Among People with HIV in the United States: A Modeling Analysis in 24 States

Zalesak, A.; Kasaie, P.; Dansky, Z.; Althoff, K. N.; Dowdy, D.; Shah, M.; Fojo, A. T.; Schnure, M.

2026-02-02 hiv aids 10.64898/2026.01.30.26345234 medRxiv
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ImportanceAs the population living with HIV in the US ages, state-level projections of the aging dynamics among people with diagnosed HIV (PWDH) will be needed to inform local planning and intervention efforts. ObjectiveWe sought to explore how aging dynamics of the population with HIV in the US are expected to differ at the state level between 2025 and 2040. Design, Setting, and ParticipantsWe projected epidemic trajectories from 2025 to 2040 in 24 US states comprising 86% of PWDH in the US using a calibrated model of HIV transmission. Main Outcomes and MeasuresWe estimated change in median age of PWDH over age 13, from 2025 to 2040, for each state. ResultsWe project that by 2040, the median age of adult PWDH in the 24 states will rise from 51 to 62 years, and over half of adult PWDH will be over the age of 65. Our projections suggest substantial heterogeneities in age distributions by state. More populous and urban states with higher median ages of PWDH in 2025 are projected to experience even further aging of the population with diagnosed HIV in the coming 15 years. By contrast, more rural and less populous states tend to have younger-aged HIV epidemics that were not projected to age substantially over time. Conclusions and RelevanceAlthough the overall population of persons with diagnosed HIV in the US is projected to age substantially, these effects will unfold differently across states. In the coming years, healthcare systems will need to plan to adapt to changing state-level demographic patterns among PWDH. Key PointsO_ST_ABSQuestionC_ST_ABSHow will the age distribution of people living with diagnosed HIV change between 2025 and 2040? FindingsUsing a calibrated model of HIV transmission in 24 US states, we project that by 2040, the median age of adult PWDH in the 24 states will rise from 51 to 62 years, and over half of adult PWDH will be over the age of 65. Our projections suggest substantial differences in age distribution by state. MeaningIn the coming years, federal and local healthcare planning will need to adapt to changing state-level demographic patterns among PWDH.

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Resilience and its determinants among adolescents and young adults with perinatally acquired HIV enrolled in a peer-led mentorship program in India

Shet, A.; Raj, M. B.; Sannigrahi, S.; Seenappa, B.; Reddy, L.; Sharma, A. A.; Narayanan, A. G.; Satish Kumar, S.; Ganapathi, L.

2026-04-11 hiv aids 10.64898/2026.04.08.26350433 medRxiv
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BackgroundAdolescents and young adults with perinatally acquired HIV (APHIV) face complex psychosocial and structural challenges that may undermine resilience, a modifiable psychosocial determinant of treatment engagement, and health outcomes. Evidence on peer-led interventions targeting resilience among APHIV in South Asia remains limited. We evaluated resilience and its correlates among participants in the ImPossible Fellowship, a peer-led mentorship intervention in India. MethodsWe conducted a cross-sectional evaluation of 216 APHIV following completion of the 24-month ImPossible Fellowship in southern India in 2024. Surveys administered by trained youth investigators assessed sociodemographic, educational, and clinical characteristics. Resilience was measured using the Child and Youth Resilience Measure-Revised (CYRM-R), a validated multidimensional tool capturing personal and relational resilience dimensions. Low resilience was defined as CYRM-R threshold score [&le;]33rd percentile. Multivariate logistic regression identified independent correlates of low resilience, and sensitivity analyses explored alternative CYRM-R thresholds. ResultsParticipants had a mean age of 18.7 years (range 9-24); 50% had no surviving parents, and 43% lived in child care institutions. Median resilience scores were high (74, Interquartile range [IQR] 69-78), and 91% achieved viral suppression. In multivariate analyses, three factors were independently associated with low resilience: loss of both parents (adjusted odds ratio [aOR] 4.35, 95% CI 2.09-9.06), school discontinuation (aOR 2.43, 95% CI 1.10-5.34), and self-reported communication barriers at HIV clinics (aOR 5.83, 95% CI 2.69-12.64). These associations were consistent across sensitivity analyses at alternative resilience thresholds. At the most stringent threshold of low resilience (CYRM-R score [&le;]15th percentile), unsuppressed viral load also emerged as a significant correlate, suggesting that treatment failure may be concentrated among those with the most severely compromised resilience. ConclusionsAPHIV participating in a peer-led mentorship program demonstrated high overall resilience and viral suppression, but also revealed addressable vulnerabilities mapping to specific programmatic priorities. Peer-led models offer a promising foundational platform; however, complementary structural and psychosocial enhancements targeting these modifiable determinants are essential to optimize outcomes for those facing the greatest cumulative adversity.

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The impact of the United States foreign aid freeze on HIV service delivery in PEPFAR-supported countries: a facility-level analysis of 2024-2025 programme data

Honermann, B.; Grimsrud, A.; Lankiewicz, E.; Sherwood, J.; Millett, G.

2026-04-20 hiv aids 10.64898/2026.04.17.26351143 medRxiv
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IntroductionOn January 20, 2025, the U.S. government froze foreign assistance including for PEPFAR, though a limited waiver for "life-saving" interventions was subsequently granted. PEPFARs 2025 monitoring results, released April 17, 2026, covered only quarter 4 while an earlier inadvertent release included all four quarters. Combining both data sets, we systematically assess facility-level programmatic performance and reporting trends to quantify service disruptions accounting for reporting discrepancies. MethodsWe categorized facilities by reporting continuity across Q1 2024 and Q4 2025 (e.g. continuous, intermittent, dropped, or new) and assessed changes in service delivery by the category of health facility for key HIV treatment, testing, PMTCT, and prevention programming. We additionally analyze changes in employed human resources for health (HRH) reported by PEPFAR. ResultsPEPFAR data included 31,746 facilities and community service sites. 71.3% were classified as continuous reporters, 16.9% intermittent reporters, 2.5% community services, 3.9% dropped in 2025, and 3.1% new in 2025. Total number of people accessing HIV treatment declined modestly by -0.3%, but differed by facility category. Continuous facilities saw a 0.5% increase in people on treatment, while intermittent facilities saw a -1.7% decrease. HIV testing declined -17%. HIV diagnoses declined -13% in continuous facilities, -35% in community services, and -29% in intermittent facilities. PMTCT infant testing and diagnoses declined by -6% and -12% in continuous facilities, respectively, and -60% and -31% in intermittent facilities, respectively. PrEP initiations declined -33%. Total direct service delivery HCWs reduced -62,541 (-24%) ConclusionThese findings reveal substantial disruptions across PEPFAR service areas, with the steepest declines among intermittent and community-based delivery sites, alongside a 24% reduction in direct service delivery healthcare workers. As potentially the final data set PEPFAR will ever release, these findings represent a troubling inflection point. The dismantling of public data systems and accountability structures undermine progress and enable programmatic gaps to develop and go unnoticed that risk allowing HIV resurgence to occur over the coming years.

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The research fatigue and beneficence scale: development and validation in a nationwide cohort of transgender women in the United States and Puerto Rico

Stevenson, M.; Reisner, S.; Pontes, C.; Linton, S.; Borquez, A.; Radix, A.; Schneider, J.; Cooney, E.; Wirtz, A.; ENCORE Study Group,

2026-04-15 epidemiology 10.64898/2026.04.13.26350829 medRxiv
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Transgender women are routinely recruited for HIV prevention research and describe feeling over-researched, undervalued, and disconnected from the benefits of research. Research fatigue refers to the adverse impacts of research participation from the volume, frequency, or intensity of research engagement. Research beneficence, an underdeveloped construct, refers to perceptions that research participation is empowering, appreciated, and beneficial to individuals and communities. This study sought to develop and psychometrically evaluate a research fatigue and beneficence scale and examine associations with cohort retention and study procedures among transgender women in the US and Puerto Rico. We developed a novel 7-item measure of research fatigue and beneficence informed by prior literature and qualitative work with transgender women. We assessed internal consistency reliability, factor structure, convergent and divergent validity, and predictive validity with 6-month study retention outcomes and procedures among 2189 transgender women enrolled in a US nationwide cohort (April 2023-December 2024) for the full 7-item research fatigue and beneficence scale, a 4-item research beneficence subscale, and a single-item research fatigue measure. Research beneficence items demonstrated good internal consistency (0.78) and excellent model fit. Research fatigue and beneficence varied by race/ethnicity with participants of color reporting both greater empowerment and greater concerns about community-level benefits. The item "I feel that I am asked to participate in research too frequently" was associated with lower 6-month retention, greater survey missingness, and preference for less invasive HIV testing modalities. Findings highlight multiple dimensions of research experience and the need for reduced participant burden, culturally tailored study designs, and intentional dissemination efforts to improve participant-centered research practices.

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HIV Treatment and Program Preferences Among Ryan White Clients in New York City in the Era of Long-Acting Injectable ART: A Discrete Choice Experiment

Zimba, R.; Kelvin, E. A.; Kulkarni, S.; Carmona, J.; Avoundjian, T.; Emmert, C.; Peterson, M.; Irvine, M.; Nash, D.

2026-02-16 hiv aids 10.64898/2026.02.13.26346257 medRxiv
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IntroductionDespite improvements in treatment for people living with HIV (PWH), adherence remains a challenge for many. In this study we aimed to identify preferences for daily pill or long-acting injectable (LAI) antiretroviral therapy (ART) and for possible treatment package features, among PWH enrolled in Ryan White HIV/AIDS Program Part A (RWPA) Medical Case Management (MCM) programs. MethodsParticipants were recruited from six MCM programs from across the New York RWPA eligible metropolitan area (the five boroughs of New York City and Rockland, Putman, and Westchester counties). We developed a discrete choice experiment (DCE) with four attributes: (1) Type of ART Medication (daily pills or LAI), (2) Service Location and Mode, (3) Support, and (4) Rewards. We used an alternative-specific design in which the levels for the last three attributes were dependent on levels within the first (Type of ART). Latent class multinomial logit analysis (LCA) was used for preference estimation and hypothesis-free investigation of preference heterogeneity. ResultsFrom June 2022 through January 2023, 200 New York RWPA MCM clients completed the DCE. We selected a two-group LCA solution. A majority of participants had a higher preference for LAI regimens compared to daily pills (n=114 [57%] versus n=86 [43%]). Those who preferred LAI ART were younger (median age 49 versus 58.5 years, p<0.001), less likely to identify as straight/heterosexual (69% versus 82%, p=0.03), and more likely to identify as Latino/a (54% versus 30%; p<0.001). Preferences for service locations/mode, supports, and rewards were similar across LCA groups. Participants who preferred LAI ART were more likely to have heard of LAI ART before the survey (59% versus 41%, p=0.012). Overall, only 4% of participants self-reported having tried LAI ART. ConclusionsAssessing preferences among groups under-represented in clinical trials is essential to effective and equitable real-world implementation of innovative treatment options. Our study found that there were distinct groups that differed in their preferred ART regimen type and that New York RWPA MCM clients had limited familiarity with LAI ART. To inform regimen selection, we began pilot-testing educational materials and a patient-provider decision-making tool in 2023.

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Evaluating Spatially Targeted HIV Interventions and Harm Reduction Services Among People Who Inject Drugs in a High-Burden Setting

Wang, J.; Clipman, S. J.; Mehta, S. H.; Srikrishnan, A. K.; Mohapatra, S.; Kumar, M. S.; Lucas, G. M.; Latkin, C. A.; Solomon, S. S.; Wesolowski, A.

2026-02-09 epidemiology 10.64898/2026.02.07.26345824 medRxiv
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People who inject drugs (PWID) in India continue to experience high HIV incidence while coverage of HIV and harm reduction services within this population remains suboptimal in many settings, highlighting the need to identify novel service delivery points. To evaluate the effectiveness of spatially focused upscaling of interventions at observed venues where PWID injected drugs together, we developed an individual-based dynamic transmission model of HIV informed by detailed injection network, service engagement, and injection venue attendance data collected in a sociometric study of PWID (n = 2512) in New Delhi, India. HIV incidence was simulated for different spatial targeting strategies and with increasing service coverage at injection venues according to UNAIDS/UNODC goals. We identified significant decreases in predicted HIV incidence when deploying interventions at frequently visited injection venues (from 6.8 cases/100 person-years to 2.7/100PY for full service coverage at the most-visited venue, and further down to 1.3/100PY for 12 most-visited venues). Prioritizing the most visited venues stratified by spatial clusters provided services to a larger number of individuals versus prioritizing the overall most visited venues, suggesting that service expansion at venues that are spatially distinct with minimal population overlap has a slightly larger impact on reducing HIV incidence.

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Reservoir and Phylogenetic Signatures Identify Distinct Subsets of HIV-1 Nonsuppressible Viremia

Adams, T.; Kang, C. K.; Mohammadi, A.; Mesquita, F.; Cohen, S.; Deligiannidis, E. A.; Edelstein, G. E.; Dorazio, D.; Kim, J.; de Andraca Serrano, A.; Moeser, M.; Hastings, L. E.; Carvalho, L.; Jordan, H.; Worrall, D. R.; Castillo-Mancilla, J. R.; Jilg, N.; Jacobson, J. M.; Tsibris, A. N.; Deeks, S.; Fletcher, C.; Llibre, J. M.; Anderson, P. L.; Zhou, S.; Joseph, S. B.; Sieg, S.; Yukl, S.; Etemad, B.; Li, J. Z.

2026-02-06 hiv aids 10.64898/2026.02.05.26345678 medRxiv
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In nonsuppressible HIV viremia (NSV), individuals have persistently detectable viral load despite adherence to [&ge;]2 fully active antiretroviral drugs. NSV represents an area of clinical uncertainty and an opportunity to understand the mechanisms of HIV persistence. We performed in-depth virologic characterization to identify distinct NSV phenotypes. We categorized participants into those who had persistent viremia after antiretroviral therapy (ART) initiation (primary NSV) and those who had NSV after a period of virologic suppression (secondary NSV). Despite the prolonged viremia, there was no significant evidence of active viral evolution in either the primary or secondary NSV groups. Primary NSV participants had >10-fold higher levels of intact proviral DNA by the intact proviral DNA assay (P<0.01). While the plasma of secondary NSV participants was dominated by a few large HIV clones, primary NSV participants had far more diverse plasma quasispecies with few clones (P<0.01). Primary NSV participants were also found to harbor distinct deletions within vif-vpr and had T-tropic virus. Transcriptional profiling of intracellular HIV RNA also suggested higher viral transcriptional activity in primary than in secondary NSV. In contrast, profiling of soluble inflammatory markers demonstrated largely comparable systemic inflammatory signatures across NSV subtypes. NSV is comprised of two distinct subsets of individuals, including a novel group with primary NSV characterized by prolonged viremia after ART initiation, an exceptionally large intact reservoir and highly diverse plasma virus populations arising from transcriptionally active proviral reservoirs, without evidence of ongoing evolution. These findings have implications for understanding mechanisms of HIV reservoir persistence on ART. One Sentence SummaryTwo distinct subsets of HIV-1 nonsuppressible viremia, primary and secondary, are identified and characterized by reservoir and phylogenetic characteristics.

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Do standard model assumptions realistically represent HIV dynamics in sex workers? A modelling analysis of South African data

Anderegg, N.; Egger, M.; Buthlezi, K.; Sinqu, Y.; Slabbert, M.; Johnson, L. F.

2026-03-10 hiv aids 10.64898/2026.03.10.26348008 medRxiv
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Female sex workers (FSW) in sub-Saharan Africa experience disproportionately high risks of HIV infection. Mathematical models are widely used to assess the contribution of sex workers and other key populations to HIV transmission dynamics and to inform targeted programmes. However, many rely on simplifying assumptions, such as stable sex worker characteristics and constant HIV transmission risk over time. These assumptions may be unrealistic and could bias modelled estimates. We used the South African Thembisa model to assess how alternative assumptions about FSW age, duration of sex work, and client-to-FSW transmission risk affect modelled HIV outcomes. We compared six scenarios that combined constant and increasing FSW age and sex work duration with constant and early-epidemic declining (exponentially or exposure-dependent) transmission risk. Each scenario was calibrated to HIV prevalence data from population-based and sex worker-specific surveys. Scenarios that allowed both FSW characteristics and transmission risk to vary over time showed the best agreement with external data, most closely reproducing HIV incidence, prevalence, and viral suppression estimates from a 2019 national sex worker survey (incidence [~]5 per 100 person-years, prevalence 61-62%, viral suppression [~]60%), and producing incidence rate ratios more consistent with estimates from the broader eastern and southern Africa region. By contrast, the scenario assuming constant FSW characteristics and transmission risk overestimated HIV incidence and underestimated prevalence and viral suppression. At the same time, this time-invariant specification attributed a much larger share of new HIV infections to sex work, with commercial sex work accounting for more than 20% of new infections in 2025, compared with 9-13% under time-varying assumptions. Overall, our findings show that HIV model estimates for sex workers are highly sensitive to modelling assumptions. Incorporating time-varying FSW parameters yields estimates that are more consistent with empirical data and support more reliable programme planning and evaluation. Author SummaryFemale sex workers in sub-Saharan Africa face much higher risks of HIV infection than other women. Mathematical models are often used to understand why and to guide prevention programmes. Yet many of these models make simple assumptions about sex workers - for example, that their average age stays the same over time, that they spend a fixed number of years in sex work, or that the chance of HIV passing from a client to a sex worker never changes. In reality, these factors changed over time. In this study, we used South Africas national HIV model to test how changing these assumptions affects the results. We compared different versions of the model and checked which ones best matched national sex worker survey data. We found that the model worked better when we allowed sex workers to become older over time, to spend longer in sex work, and the risk of passing on HIV to decline. Our findings show that mathematical models can give very different answers depending on how they represent the lives and experiences of sex workers. More realistic assumptions lead to more accurate estimates and can help ensure that programmes focus support where it is most needed.

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Aligning Definitions with Realities: An Interpretive Descriptive Study on the Complexities of Measuring Retention in HIV Care in the Global Context

Rehman, N.; Guyatt, G.; Sabin, L. L.; Xiong, J.; English, M. G.; Rae, G. M.; Haberer, J. E.; Mugavero, M.; Giordano, T. P.; Mertz, D.; Jones, A.

2026-02-16 hiv aids 10.64898/2026.02.13.26345822 medRxiv
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BackgroundRetention in HIV care is associated with higher rates of antiretroviral treatment adherence and viral suppression, as well as lower risk of AIDS-related morbidity and mortality. However, the multidimensional nature of retention complicates measurement standardization, limiting comparability and global evaluation. This study explored how HIV stakeholders define and assess retention, aiming to develop a patient-centred and conceptually robust understanding to inform research and practice. MethodsWe conducted a qualitative study using Interpretive Description (ID) methodology, an applied qualitative approach designed to generate practice-relevant knowledge in health research. We purposively sampled 20 stakeholders representing diverse areas of expertise and geographic regions across World Bank country income classifications. We conducted, video-recorded, and transcribed in-depth, semi-structured interviews. Using constant comparative analysis (CCA), we identified recurring, convergent, and contradictory patterns. ResultsThe analysis identified five overarching themes. The first two, exploratory themes, included: Patient-Centred Understanding of Retention in HIV Care, which captured how stakeholders conceptualized retention in their respective contexts, and Operationalization of Retention Measures, which explored the key components used to measure retention. The next two, explanatory themes, included Purpose-Driven Definitions of Retention, which described how retention measures were selected based on their intended use; and Building Capacity through Shared Understanding and Integrated Action, which emphasized retention as a cyclical, interconnected process dependent on collaboration between patients and health systems. The final, prescriptive theme, Advancements Shaping Retention, reflected stakeholders shared vision of improving retention through innovations in HIV treatment and technology. ConclusionsThe findings suggest that stakeholders operationalize retention measures in line with specific objectives and individual health goals, while remaining attentive to contextual realities. Retention measures should remain flexible and patient-centred, rather than relying on a single rigid standard.

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The direct implementation costs of HIV pre-exposure prophylaxis in Lesotho and Zimbabwe: a costing study of PrEP choice involving oral pills, the dapivirine ring, and long-acting injectable cabotegravir to inform policy setting

Corlis, J.; Bollinger, L.; Mangenah, C.; Ncube, G.; Marake-Raleie, N.; Soothoane, R.; Gwavava, E.; Yemeke, T.; Eichleay, M.; Kapuganti, S.; Stegman, P.; Bellows, N.; Kripke, K.

2026-03-06 hiv aids 10.64898/2026.03.05.26347680 medRxiv
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Because of its recent regulatory approval in southern and eastern Africa, CAB PrEP represents a scientific advancement with unknown implementation costs in most African countries. To our knowledge, this paper is the first study comparing PrEP costs in health facilities where clients had a choice between three PrEP methods. We collected and analyzed the direct service delivery costs for each method using the same costing approach and assumptions at three facilities in Lesotho and six facilities in Zimbabwe. On average, in Lesotho, the direct costs of providing CAB PrEP were $57.22 for an initiation visit and $54.20 for a refill visit (same PrEP product dose dispensed in both visit types), while the direct costs of oral PrEP were $22.47 (initiation visit with one month of PrEP dispensed) and $31.98 (refill visit dispensing a three-month dose of medication), and the direct costs of the dapivirine ring were $34.27 (initiation visit with one month of PrEP dispensed) and $50.70 (refill visit dispensing a three-month supply). In Zimbabwe, the average per-visit direct costs to provide CAB PrEP were $48.26 (initiation visit) and $47.40 (refill visit), to provide oral PrEP were $13.47 (initiation visit with one month of PrEP dispensed) and $21.78 (refill visit dispensing a three-month dose), and to provide the dapivirine ring were $42.56 (refill visit dispensing a three-month supply). Initiation visits for the dapivirine ring were not observed in Zimbabwe. At a time when national governments are creating budgets for the HIV response with decreased financial support from bilateral and multilateral partners, this paper will inform HIV prevention planning by providing critical client-level data from the healthcare provider perspective.

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Behavioral Risk Identification and Decision Guidance for Engagement (BRIDGE): Research protocol for an evaluation of an HIV treatment retention toolkit for the early treatment period

Sande, L.; Maskew, M.; Mutanda, N.; Kuchingwe, E.; Morgan, A.; Ntijekelane, V.; Chiwaye, S.; Benade, M.; Marri, A. R.; Malala, L.; Manganye, M.; Rosen, S.; Scott, N. A.

2026-03-26 hiv aids 10.64898/2026.03.24.26349199 medRxiv
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Background Interruptions in HIV care pose a major challenge to achieving HIV control goals in many countries, with 30% of clients who initiate antiretroviral therapy (ART) in South Africa experiencing an interruption of >28 days during their first six months on treatment. South Africa introduced revised guidelines in 2023 to improve outcomes during this early treatment period, but guideline compliance remains incomplete and gaps in the support provided to both clients and providers to optimize service delivery and health outcomes. Protocol BRIDGE (Behavioral Risk Identification and Decision Guidance for Engagement) is a mixed-methods evaluation of a package of light-touch, low-cost interventions aimed at improving the experiences of both clients and providers of care, increasing compliance with the 2023 guidelines, supporting clients to remain in care, and ultimately reducing the incidence of missed visits during the early treatment period. Components of the BRIDGE Retention Toolkit include an intervention navigator to help clients self-assess areas of vulnerability for disengagement from care and identify appropriate interventions; client roadmap to explain the treatment journey for the early treatment period; WhatsApp-based counseling tool for clients; guideline reference for providers; and tracing job aids. The tookit will be piloted at 6-8 public sector primary health facilities for a one-month period. The primary outcome will be the probability of returning less than 28 days late for the next scheduled clinic visit, assessed using electronic medical record data for the pilot and comparison sites. Pilot outcomes will be compared to both their own probabilities prior to the pilot and to probabilities from comparable non-pilot facilities. Implementation outcomes to be assessed using qualitative interview data from both clients and providers will include reach, implementation fidelity, adoption (uptake), costs, feasibility, appropriateness, and acceptability. Discussion The evaluation will assess the implementation and preliminary effectiveness of a set of interventions designed to improve client outcomes during the early HIV treatment period. If some or all of the BRIDGE tools are found to be helpful and/or are associated with a reduction in missed clinic visits, they will comprise a readily scalable and affordable intervention to help address a major barrier in large-scale HIV treatment programs.

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Time to registry discontinuity in Tanzania's national HIV care registry: a survival analysis of population mobility patterns

Mwakyomo, J.; Sangeda, R. Z.; Mushi, H.; Njau, P.

2026-03-09 hiv aids 10.64898/2026.03.07.26347830 medRxiv
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BackgroundEarly loss to follow-up (LTFU) after HIV enrolment is widely used to monitor program performance and progress toward treatment targets. These indicators assume that absence from the registering clinic reflects disengagement from care. However, in settings with substantial internal migration, patients may continue treatment at another facility while appearing to be lost in routine records. We evaluated the timing and geographic patterns of registry discontinuity following HIV registration in Tanzania to assess whether early LTFU primarily reflects patient disengagement from care or the characteristics of the monitoring system. MethodsWe conducted a national registry-based observational analysis using routinely collected data from the HIV care registry maintained by the National AIDS and Sexually Transmitted Infections Control Programme (NASHCoP). The analysis included 2,136,207 individuals with recorded district registration and visit dates between 2017 and 2021. Registry discontinuity was defined as the interval between the first recorded visit and the absence of further recorded visits within the registration facility. Kaplan-Meier methods were used to estimate time-to-discontinuity patterns, and persistence curves were compared across predefined population mobility corridors (stable districts, urban migration districts, mining areas, pastoralist regions, and border districts). Threshold summaries were calculated at 30, 60, 90, and 180 days. ResultsThe median duration between the first and last recorded visits was 777 days (IQR, 217-1659). Registry discontinuity occurred predominantly soon after registration: 9.6% of individuals had no further recorded visits within 30 days, 11.8% within 60 days, 13.5% within 90 days, and 17.8% within 180 days of registration. A Kaplan-Meier analysis showed a steep early decline, followed by a prolonged plateau, indicating that most discontinuities occurred shortly after the first recorded visit. The time to registry discontinuity differed significantly across mobility corridors (log-rank p < 0.001), with earlier discontinuities in border, urban-migration, and mining districts compared with stable districts. Nearly one million individuals were recorded as newly registered in 2017, suggesting that first registry appearance frequently reflects administrative enrolment rather than first lifetime initiation of HIV care. ConclusionsEarly registry discontinuity following HIV registration in Tanzania is common, occurring soon after the first recorded visit, and shows a consistent geographic structure associated with population mobility. These findings indicate that a substantial proportion of apparent early LTFU reflects administrative discontinuity rather than confirmed treatment interruption. Facility-based retention indicators may therefore underestimate treatment continuity among mobile populations. Monitoring systems capable of linking patient records across facilities and administrative boundaries are required to distinguish between geographic relocation and disengagement from care.

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Comparative 48-Week Viral Load Suppression across Antiretroviral Initiation Regimens: Dolutegravir versus Non-Dolutegravir among People Living with HIV in Tanzania

Kayange, G. F.; Sangeda, R. Z.; Njau, P.

2026-03-23 hiv aids 10.64898/2026.03.19.26348839 medRxiv
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BackgroundRoutine viral load monitoring is central to assessing treatment effectiveness in HIV care, and dolutegravir (DTG)-based regimens are now preferred in many treatment programmes. However, national routine data analyses comparing 48-week viral load suppression across antiretroviral therapy initiation regimens in Tanzania remain limited. MethodsWe conducted a retrospective cohort analysis using routinely collected HIV programme data from Tanzanias National AIDS, STIs and Hepatitis Control Programme database. After de-duplication and data processing, the working analysis warehouse contained 49,547 patients and 1,008,137 visits. The primary analysis included 6,991 patients with a valid viral load measured 48 weeks after initiation of antiretroviral therapy. Viral suppression was defined as a viral load <1,000 copies/mL. We compared suppression between DTG-based and non-DTG-based initiation groups and across individual initiation regimens. Treatment change episodes and early DTG switching patterns were summarized as secondary analyses. ResultsOf the 6,991 included patients, 6,113 (87.4%) achieved viral load suppression at 48 weeks. Suppression was higher among DTG initiators than non-DTG initiators (917/1,000, 91.7% vs. 5,196/5,991, 86.7%). TDF+3TC+EFV was the most common non-DTG initiation regimen, whereas TDF+3TC+DTG was the most common regimen among DTG initiators. ConclusionsViral suppression at 48 weeks was high overall but was higher among patients initiated on DTG-based regimens than among those initiated on non-DTG regimens. By anchoring outcomes to a fixed post-initiation time point, this study complements existing Tanzanian evidence on viral load testing uptake and geographic variation. It provides regimen-specific insights into the effectiveness of early treatment under routine programme conditions.

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HIV viral non-suppression and drug resistance among persons who inject drugs on dolutegravir antiretroviral therapy in Kenya

Mbogo, L. W.; Boyce, C. L.; Sambai, B.; Hawes, S. E.; Guthrie, B. L.; Min, W. S. D.; Kimani, D.; Adhanja, V.; Chohan, B. H.; Smith, R. A.; Monroe-Wise, A.; Gitau, E.; Masyuko, S.; Marconi, V. C.; Gottlieb, G. S.; Drain, P. K.; Frenkel, L. M.; Farquhar, C.

2026-03-02 hiv aids 10.64898/2026.02.26.26347230 medRxiv
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BackgroundMaintaining viral suppression among people who inject drugs (PWID) living with HIV in sub-Saharan Africa remains critical to minimize drug resistance for dolutegravir (DTG)-based regimens. We evaluated PWID taking DTG to assess longitudinal rates of viral non-suppression and emergence of drug resistance mutations in Kenya. MethodsWe enrolled Kenyan PWID who had transitioned from an efavirenz (EFV) based regimen to tenofovir+lamivudine+DTG (TLD) [&ge;]6 months prior, and measured plasma HIV RNA viral load (VL) every 6 months for 2 years. We used univariable Cox proportional hazards to assess longitudinal risk for viremia (VL >200 copies/ml). Plasma specimens with viremia were genotyped for HIV drug resistance, including minority variants, using a lab-developed PacBio sequencing assay, and referenced by the Stanford HIVdb program. ResultsAmong 250 participants, 125 were receiving methadone, 199 (79.6) reported heroin use, 70% were male, and median age was 39 years. 194 (77.6%) participants completed all five study visits, 41 (16.4%) were lost to follow-up and 15 (6.0%) died. Across all study visits, 166 (66.0%) of the 250 participants were always suppressed, and 84 (33.6%) were viremic at least once during follow-up, including 8 (3.2%) who were always viremic and 76 (30.4%) who were intermittently suppressed. Living in an improvised shelter or outdoors was significantly associated with a higher risk of viremia (HR=4.35, 95% CI: 1.52-12.53). 93 specimens had drug resistance genotyping, 27 (29%) of which were from participants with incomplete follow-up. NNRTI resistance was frequent (37-41% across visits), whereas major resistance mutations were infrequent to tenofovir (4.3%), lamivudine (7.5%), and DTG (1%, minority variant S153F detected at 1% frequency). Accessory DTG mutations, which do not independently reduce susceptibility, were more common, observed in 41% (38/93) of genotyped specimens, most often T97A, E138K, and L74M. ConclusionAmong PWID living with HIV on TLD in Kenya, one-third had intermittent or sustained viral non-suppression across two years of follow-up. While NNRTI resistance was common, DTG resistance mutations were rare. Improving viral suppression among PWID living with HIV will reduce transmission risks and improve clinical outcomes.

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The impact of USAID and CDC funding cuts on HIV incidence and mortality in KwaZulu Natal, South Africa

Shenoi, S. V.; Moll, A. P.; Yoo, Y. R.; Zama, P.; George, G.; Morojele, N.; Mbaya, J.; Govender, K.; Sunpath, H.; Gasa, S.; De Wet, C.; Jeetoo, M.; Ndabandaba, T.; Charles, D.; Braithwaite, R. S.

2026-02-22 hiv aids 10.64898/2026.02.18.26346597 medRxiv
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BackgroundAbrupt cessation of USAID and CDC resources to KwaZulu Natal province in South Africa, threatens the progress over decades to address HIV. MethodsWe used a previously developed validated HIV transmission model with input from the KZN Department of Health and local stakeholders to estimate impact of funding cuts on HIV incidence and mortality at 12-months and through 2030. We applied the model to estimate the impact of restoring funds on HIV incidence and mortality. ResultsHIV incidence increased at 12 months and through 2030 by 3.4% and 22.8%, leading to 35,300 and 116,100 additional infections, and 12,800 and 42,300 additional deaths, respectively. Restoring funding after a 12-month pause, reallocated to focus on long-acting PrEP, would avert 12,600 new infections. ConclusionThis model application demonstrates that the sudden cessation of USAID and CDC commitments in the largest HIV epidemic in the world leads to increased incidence and mortality and threatens decades of progress in KZN, South Africa. Restoring funding within 12 months and increasing efficiency of HIV interventions can reestablish KwaZulu Natal province, South Africas trajectory toward EHE goals.