Refining and Optimizing Theory-Based Peer-Delivered HIV Prevention Interventions for Transgender Men Who Have Sex with Men: Lessons Learned from The TOGETHR Study (Preprint)

2026-04-08

<sec> <title>BACKGROUND</title> Transgender men and transmasculine people who have sex with men (TMSM) are at elevated risk for HIV acquisition, have unmet HIV prevention needs, and have low uptake of antiretroviral pre-exposure prophylaxis (PrEP). To our knowledge, there are no published efficacious behavioral interventions to decrease HIV risk specifically for TMSM; this includes peer-delivered strategies that demonstrate high acceptability in this population. </sec> <sec> <title>OBJECTIVE</title> This paper describes the development, refinement, and optimization of theory-informed, peer-delivered digital interventions—which were feasible to implement and highly acceptable among the participant population—designed to increase PrEP uptake and adherence among adult transmasculine people who have sex with individuals assigned male at birth within the context of a full-scale, randomized factorial trial. </sec> <sec> <title>METHODS</title> Between March 2023-March 2025, we used an iterative community-engaged approach that included: (1) community and key stakeholder input, (2) theory- and evidence-informed manualized content with iterative refinement, (3) interventionist training and preparation, and (4) process evaluation and fidelity monitoring. Two theoretical frameworks and one theory of behavior change guided content development, structure, format and evaluation: The Healthcare Accessibility Framework, the Gender Affirmation Framework, and the Information, Motivation, and Behavioral Skills Model of behavior change. </sec> <sec> <title>RESULTS</title> A 4-member Community Advisory Board of transmasculine individuals partnered with the research team to co-design interventions and study procedures. Additional input was obtained through one-on-one key stakeholder consultations with nine topic experts, clinicians, and community experts at partner organizations. Iterative refinement incorporated evidence synthesis, manual drafting, mock sessions, and structured feedback loops resulting in two refined virtually delivered interventions: (1) PrEP4T, a 6-session one-on-one peer navigation intervention (60-90 minutes/session) emphasizing goal setting, harm reduction, and supportive referrals; and (2) LS4TM, a 6-session peer-facilitated group-based behavioral intervention (2 hours/session), focusing on sexual health knowledge, gender affirmation, communication, and social support. A digital standard of care (SOC) resource guide of curated, gender-affirming sexual health, HIV prevention, and community resources was also developed. Interventionist training included approximately 15 hours of knowledge/skill building (asynchronous and live didactic sessions) and at least 12 hours of applied practice (mock sessions with structured feedback). Process evaluation and fidelity relied on participant- and interventionist-completed case reporting forms, reflecting community prioritization of interventionist and participant comfort during sessions. Key lessons learned included the importance of flexible, manualized intervention content structures that support fidelity while allowing personalized adaptation; using gender-affirming language through mirroring and dual phrasing; centering “voice” and “choice” in HIV prevention decision-making; incorporating behavior change scaffolding (e.g., goal setting, elicit-provide-elicit techniques); offering hands-on peer navigation and curated SOC resources to address structural access barriers; and leveraging digital tools to enhance engagement, shared learning, and community connection. </sec> <sec> <title>CONCLUSIONS</title> Co-designing with transmasculine communities through an iterative, community-engaged development and refinement processes was essential for producing culturally responsive, theoretically-grounded, and gender-affirming HIV prevention interventions. Our findings can inform future peer-delivered and digital HIV prevention strategies tailored to the needs of specific populations, grounded in community partnerships and lived experience. </sec> <sec> <title>CLINICALTRIAL</title> ClinicalTrials.gov NCT06182280; https://clinicaltrials.gov/ct2/show/NCT06182280 </sec> <sec> <title>INTERNATIONAL REGISTERED REPORT</title> RR2-10.2196/76831 </sec>

The Impact of Childhood Household Violence on HIV-Related Outcomes in People With HIV in the United States: The Role of Psychological Distress and Social Stressors

JAIDS Journal of Acquired Immune Deficiency Syndromes · 2025-12-11

BACKGROUND: Psychological distress (eg, depression) and social stressors (eg, HIV-related stigma) can affect HIV-related outcomes such as antiretroviral therapy adherence and health-related quality of life (HRQL). Limited research on adverse childhood experiences such as childhood household violence (CHV) has shown a similar impact on HIV-related outcomes, particularly virologic suppression, although little is known about mediating pathways with factors such as psychological distress and social stressors. SETTING: Data from the Centers for AIDS Research Network of Integrated Clinical Systems cohort were analyzed. This article examines the relationship between CHV and HIV-related outcomes, and potential differences between those with and without CHV by age (<50 vs. ≥50 years). METHODS: Bivariate comparisons, linear regressions, and mediation analyses between CHV and other variables were used to assess association with outcome measures. RESULTS: Among 7705 people with HIV, CHV was reported by 19% (n = 1498). CHV was associated with lower antiretroviral therapy adherence (P < 0.001), more HIV symptoms (P < 0.001), and lower HRQL (P < 0.001). In addition, CHV exposure was associated with worse depressive symptoms (P < 0.001), increased panic symptoms (P < 0.001), lower social support (P < 0.001), greater self-report of HIV stigma (P < 0.001), and more exposure to intimate partner violence (P < 0.001). Psychological distress and social stressors mediated the relationship between CHV and adherence, HIV symptoms, and HRQL, with depressive and panic symptoms accounting for the greatest proportion mediated. CONCLUSIONS: CHV has an adverse impact on social and psychological factors in adulthood for people with HIV. Depressive symptoms and panic symptoms are potential targets for interventions.

Efficacy and safety of a mosaic HIV-1 vaccine regimen in men who have sex with men and transgender individuals (HVTN 706/HPX3002/Mosaico): a global, randomised, double-blind, placebo-controlled, phase 3 trial

The Lancet HIV · 2025-11-27 · 2 citations

Innovations in the biomedical prevention, diagnosis, and service delivery of HIV and other sexually transmitted infections

The Lancet · 2025-10-30 · 14 citations

Differences in Methamphetamine Use, Self-Reported Impact, and HIV-Related Outcomes by Gender and Sexual Orientation in a Multisite U.S. Cohort of People with HIV in Care

AIDS and Behavior · 2025-09-28

Longitudinal Associations Between Internalized HIV Stigma and Lower HIV Antiretroviral Therapy Adherence Among People With HIV

JAIDS Journal of Acquired Immune Deficiency Syndromes · 2025-11-06

BACKGROUND: Internalized HIV stigma (IHS) is associated with reductions in antiretroviral therapy (ART) adherence and HIV viremia mediated through depression. However, there is still a need to quantify the direct impact of IHS on ART adherence to inform interventions to improve medication adherence. METHODS: The Center for AIDS Research Network of Integrated Clinical Systems is a longitudinal, US-based, multisite cohort of people with HIV who complete patient-reported outcome assessments as part of HIV-care visits. Patient-reported outcome data include IHS items, ART adherence, depression assessments, substance use, and other outcomes. We examined associations between IHS and ART adherence using generalized linear latent and mixed models with a nonparametric random effects intercept to accommodate repeated measures. Results were compared with analyses using generalized estimating equations and marginal structural models. RESULTS: Among 13,119 people with HIV, the mean age was 47.4 years, 17.6% were women, and 59.3% were non-White. Across 33,139 observations, controlled for repeated measures on individuals, HIV medication adherence was reduced by 1.07% for every point increase in IHS after controlling for age, sex, ethnicity, geographic location, and substance use, and 0.58% when additionally adjusted for depression score. Marginal structural models and generalized estimating equations provided similar results. CONCLUSIONS: Our study demonstrates that IHS has a direct association with reductions in ART adherence, which could affect other comorbid health outcomes that are influenced by unsuppressed viremia over time. Developing a thorough understanding of the mechanisms through which IHS affects ART adherence is critical for developing interventions to mitigate IHS and improve health outcomes across the lifespan.

Association between housing instability and frailty among people with HIV

AIDS · 2025-10-06

BACKGROUND: Housing instability and HIV are both associated with early onset of aging-related health conditions, including frailty. However, little is known about the relationship between housing and frailty among people with HIV. METHODS: We analyzed data on adults in HIV care collected during routine clinical visits at 6 sites within the US Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) between 2019 and 2024. We measured frailty using a previously validated approach, defined as having at least three of four components (fatigue, weight loss, immobility, inactivity) vs. less than three components. Housing status was based on self-perceived living situation in the past month ("Stable," "Unstable," "Homeless," or "Don't know"). We estimated the association between most recent housing status and frailty with prevalence ratios from relative risk regression adjusted for sociobehavioral and clinical characteristics. RESULTS: Among 6961 people with HIV (84% men, 16% women) with a median age of 52 years (IQR: 40-60), 11% ( n = 760) were frail and 9% ( n = 625) were unstably housed (5% unstable, 3% homeless, 1% do not know). Compared to individuals with stable housing, the prevalence of frailty more than doubled among those experiencing unstable housing [prevalence ratio = 2.41, 95% confidence interval (95% CI): 1.95-2.97] or homelessness (prevalence ratio = 2.05, 95% CI: 1.56-2.69). Stratified analyses indicated stronger associations among younger vs. older individuals and among those virally suppressed vs. unsuppressed. CONCLUSION: Housing instability and frailty were both prevalent and strongly associated among adults in HIV care, including within younger and virally suppressed subgroups. These findings highlight the importance of social determinants of health for clinical outcomes among all people with HIV.

Validation of the PrEP Use Self-Efficacy (PrEP-Use) Scale Among Sexual Minority Men

AIDS Education and Prevention · 2025-10-01

Self-efficacy may influence several stages of the PrEP care continuum, yet most validated measures capture only one component rather than a comprehensive approach. To address this gap, this study validated the PrEP Use Self-Efficacy (PrEP-USE) scale. Sexual minority men (N = 300) prescribed daily oral PrEP completed a baseline assessment including sociodemographics, the PrEP-USE scale, self-reported adherence, and PrEP-related variables (attitudes, stigma, subjective and descriptive norms) as part of a larger randomized controlled trial. Exploratory factor analysis identified a three-factor model (Challenges, Management, Routine) with acceptable fit. Overcoming challenges was associated with PrEP adherence (b = 1.09, p &lt; .01) and correlated with all PrEP-related variables (p &lt; .05). Management correlated with all variables (p &lt; .05) but not adherence. Routine was associated with adherence (b = 2.42, p &lt; .001) and only with PrEP attitudes (p &lt; .05). Integrating the PrEP-USE scale into intervention frameworks may strengthen self-efficacy measurement.

Age modifies the association between sex and the plasma inflammatory proteome in treated HIV

Journal of Clinical Investigation · 2025-12-09 · 1 citations

BACKGROUNDAmong antiretroviral therapy-suppressed (ART-suppressed) people with HIV (PWH), women have higher levels of some inflammatory markers than men, but the effect of sex on the inflammatory proteome, and whether age modifies these differences, remain unclear.METHODSPlasma inflammatory protein levels were assessed in ART-suppressed PWH from the Center for AIDS Research Network of Integrated Clinical Systems. The relationship between sex and plasma proteins - including 22 interferon-α response pathway proteins - was assessed, adjusting for confounders and assessing interactions by age.RESULTSOf 922 participants, 162 (18%) were female. The median age was 47, above which the majority of women had undetectable plasma anti-Müllerian hormone levels, a biomarker of ovarian reserve. Age modified the influence of sex on the inflammatory proteome. Older age (>47) was associated with greater increases among women than men in 194 proteins. Interferon-α response proteins were higher in men in those ≤ 47 but higher in women in those > 47 (interaction P < 0.001). Among the 131 proteins associated with mortality risk (q < 0.05), only 5 differed by sex among those ≤ 47, while 79 differed by sex in those > 47, with nearly all being higher in women. Women had decreased mortality than men ≤ 47 (P < 0.001) but had similar mortality > 47 (P = 0.84).CONCLUSIONThe menopausal transition appears to increase systemic type I interferon responses and inflammation in women with HIV, which may contribute to a loss of female advantage in mortality.FUNDINGNIH National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; National Institute of Allergy and Infectious Diseases.

Partial progress in sexual and reproductive health and rights: the influence of sociocultural, behavioural, structural, and technological changes on epidemiological trends

The Lancet · 2025-10-30 · 10 citations