Enhanced Cohort Methods for HIV Research and Epidemiology (ENCORE): Protocol for a Nationwide Hybrid Cohort for Transgender Women in the United States.

BACKGROUND: In the United States, transgender women are disproportionately impacted by HIV and prioritized in the national strategy to end the epidemic. Individual, interpersonal, and structural vulnerabilities underlie HIV acquisition among transgender women and fuel syndemic conditions, yet no nationwide cohort monitors their HIV and other health outcomes. OBJECTIVE: Our objective is to develop a nationwide cohort to estimate HIV incidence, identify risk factors, and investigate syndemic conditions co-occurring with HIV vulnerability or acquisition among US transgender women. The study is informed by the Syndemics Framework and the Social Ecological Model, positing that stigma-related conditions are synergistically driven by shared multilevel vulnerabilities. METHODS: To address logistical and cost challenges while minimizing technology barriers and research distrust, we aim to establish a novel, hybrid community hub-supported digital cohort (N=3000). The digital cohort is the backbone of the study and is enhanced by hubs strategically located across the United States for increased engagement and in-person support. Study participants are English or Spanish speakers, are aged ≥18 years, identify as transgender women or along the transfeminine spectrum, reside in 1 of the 50 states or Puerto Rico, and do not have HIV (laboratory confirmed). Participants are followed for 24 months, with semiannual assessments. These include a questionnaire and laboratory-based HIV testing using self-collected specimens. Using residential zip codes, person-level data will be merged with contextual geolocated data, including population health measures and economic, housing, and other social and structural factors. Analyses will (1) evaluate the contribution of hub support to the digital cohort using descriptive statistics; (2) estimate and characterize syndemic patterns among transgender women using latent class analysis; (3) examine the role of contextual factors in driving syndemics and HIV prevention over time using multilevel regression models; (4) estimate HIV incidence in transgender women and examine the effect of syndemics and contextual factors on HIV incidence using Poisson regression models; and (5) develop dynamic, compartmental models of multilevel combination HIV prevention interventions among transgender women to simulate their impact on HIV incidence through 2030. RESULTS: Enrollment launched on March 15, 2023, with data collection phases occurring in spring and fall. As of February 24, 2024, a total of 3084 individuals were screened, and 996 (32.3%) met the inclusion criteria and enrolled into the cohort: 2.3% (23/996) enrolled at a hub, and 53.6% (534/996) enrolled through a community hub-supported strategy. Recruitment through purely digital methods contributed 61.5% (1895/3084) of those screened and 42.7% (425/996) of those enrolled in the cohort. CONCLUSIONS: Study findings will inform the development of evidence-based interventions to reduce HIV acquisition and syndemic conditions among US transgender women and advance efforts to end the US HIV epidemic. Methodological findings will also have critical implications for the design of future innovative approaches to HIV research. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59846.

Stigma, social and structural vulnerability, and mental health among transgender women: A partial least square path modeling analysis.

INTRODUCTION: Existing literature suggests that transgender women (TW) may be at high risk for adverse mental health due to stress attributed to combined experiences of stigma and complex social and structural vulnerabilities. Little research has examined how these co-occurring experiences relate to mental health. We aimed to test a theoretically driven conceptual model of relationships between stigma, social and structural vulnerabilities, and mental health to inform future intervention tailoring. DESIGN/METHODS: Partial least square path modeling followed by response-based unit segmentation was used to identify homogenous clusters in a diverse community sample of United States (US)-based TW (N = 1418; 46.2% White non-Hispanic). This approach examined associations between latent constructs of stigma (polyvictimization and discrimination), social and structural vulnerabilities (housing and food insecurity, unemployment, sex work, social support, and substance use), and mental health (post-traumatic stress and psychological distress). RESULTS: The final conceptual model defined the structural relationship between the variables of interest within stigma, vulnerability, and mental health. Six clusters were identified within this structural framework which suggests that racism, ethnicism, and geography may be related to mental health inequities among TW. CONCLUSION: Our findings around the impact of racism, ethnicism, and geography reflect the existing literature, which unfortunately shows us that little change has occurred in the last decade for TW of color in the Southern US; however, the strength of our evidence (related to sampling structure and sample size) and type of analyses (accounting for co-occurring predictors of health, i.e., stigma and complex vulnerabilities, reflecting that of real-world patients) is a novel and necessary addition to the literature. Findings suggest that health interventions designed to offset the negative effects of stigma must include anti-racist approaches with components to reduce or eliminate barriers to resources that contribute to social and structural vulnerabilities among TW. Herein we provide detailed recommendations to guide primary, secondary, and tertiary prevention efforts. CLINICAL RELEVANCE: This study demonstrated the importance of considering stigma and complex social and structural vulnerabilities during clinical care and design of mental health interventions for transgender women who are experiencing post-traumatic stress disorder and psychological distress. Specifically, interventions should take an anti-racist approach and would benefit from incorporating social support-building activities.

Access to healthcare among transgender women living with and without HIV in the United States: associations with gender minority stress and resilience factors.

BACKGROUND: Transgender women (TW) experience significant inequities in healthcare access and health disparities compared to cisgender populations. Access to non-transition related healthcare is understudied among TW. We aimed to assess the association between access to care and gender minority stress and resilience factors among TW living with and without HIV in eastern and southern United States. METHODS: This study was a cross-sectional analysis of baseline data drawn from a cohort of 1613 adult TW from the LITE Study. The cohort permitted participation through two modes: a site-based, technology-enhanced mode and an exclusively online (remote) mode. Exploratory and confirmatory factor analyses determined measurement models for gender minority stress, resilience, and healthcare access. Structural equation modeling was used to assess the relationships between these constructs. Models were evaluated within the overall sample and separately by mode and HIV status. RESULTS: Higher levels of gender minority stress, as measured by anticipated discrimination and non-affirmation were associated with decreased access to healthcare. Among TW living with HIV, higher levels of anticipated discrimination, non-affirmation, and social support were associated with decreased healthcare access. Among TW living without HIV in the site-based mode, resilience was positively associated with positive healthcare experiences and inversely associated with barriers to healthcare access. Among TW living without HIV in the online mode, anticipated discrimination was associated with barriers to healthcare access; resilience was positively associated with positive healthcare experiences and inversely associated with barriers to healthcare access. CONCLUSIONS: Gender minority stress was associated with increased barriers to healthcare access among TW in the US, regardless of HIV status. Resilience factors did not mediate this effect. Interventions aiming to increase healthcare access among TW can be aided by efforts to mitigate drivers of gender minority stress and improve patient experiences in healthcare facilities.

PrEP initiation and discontinuation among transgender women in the United States: a longitudinal, mixed methods cohort study.

INTRODUCTION: Transgender women in the United States experience high HIV incidence and suboptimal Pre-exposure prophylaxis (PrEP) engagement. We sought to estimate PrEP initiation and discontinuation rates and characterize PrEP discontinuation experiences among a prospective cohort of transgender women. METHODS: Using a sequential, explanatory, mixed-methods design, 1312 transgender women at risk for HIV acquisition were enrolled from March 2018 to August 2020 and followed through July 2022 (median follow-up 24 months; interquartile range 15-36). Cox regression models assessed predictors of initiation and discontinuation. In-depth interviews were conducted among 18 participants, including life history calendars to explore key events and experiences surrounding discontinuations. Qualitative and quantitative data were integrated to generate typologies of discontinuation, inform meta-inferences and facilitate the interpretation of findings. RESULTS: 21.8% (n = 286) of participants reported taking PrEP at one or more study visits while under observation. We observed 139 PrEP initiations over 2127 person-years (6.5 initiations/100 person-years, 95% CI: 5.5-7.7). Predictors of initiation included identifying as Black and PrEP indication. The rate of initiation among those who were PrEP-indicated was 9.6 initiations/100 person-years (132/1372 person-years; 95% CI: 8.1-11.4). We observed 138 PrEP discontinuations over 368 person-years (37.5 discontinuations/100 person-years, 95% CI: 31.7-44.3). Predictors of discontinuation included high school education or less and initiating PrEP for the first time while under observation. Four discontinuation typologies emerged: (1) seroconversion following discontinuation; (2) ongoing HIV acquisition risk following discontinuation; (3) reassessment of HIV/STI prevention strategy following discontinuation; and (4) dynamic PrEP use coinciding with changes in HIV acquisition risk. CONCLUSIONS: PrEP initiation rates were low and discontinuation rates were high. Complex motivations to stop using PrEP did not consistently correspond with HIV acquisition risk reduction. Evidence-based interventions to increase PrEP persistence among transgender women with ongoing acquisition risk and provide HIV prevention support for those who discontinue PrEP are necessary to reduce HIV incidence in this population.

HIV incidence and mortality in transgender women in the eastern and southern USA: a multisite cohort study.

BACKGROUND: Epidemiological monitoring of HIV among transgender women is minimal despite prioritisation of this group in the US National HIV/AIDS Strategy (2022-2025). We aimed to estimate HIV incidence in a multisite cohort of transgender women in the eastern and southern USA. Participant deaths were identified during follow-up; thus, we felt it was an ethical imperative to report mortality alongside HIV incidence. METHODS: In this study, we established a multisite cohort across two modes: a site-based, technology-enhanced mode in six cities (Atlanta, Baltimore, Boston, Miami, New York City, and Washington, DC) and an exclusively digital mode that spanned 72 eastern and southern US cities that matched the six site-based cities based on population size and demographics. Trans feminine adults (≥18 years) who were not living with HIV were eligible and followed up for at least 24 months. Participants completed surveys and oral fluid HIV testing with clinical confirmation. We ascertained deaths through community and clinical sources. We estimated HIV incidence and mortality using the number of HIV seroconversions and deaths, respectively, divided by person-years accumulated from enrolment. Logistic regression models were used to identify predictors of HIV seroconversion (primary outcome) or death. FINDINGS: Between March 22, 2018, and Aug 31, 2020, we enrolled 1312 participants with 734 (56%) in site-based and 578 (44%) in digital modes. At the 24-month assessment, 633 (59%) of 1076 eligible participants consented to extending participation. 1084 (83%) of 1312 participants were retained at this analysis based on the study definition of loss to follow-up. As of May 25, 2022, the cohort participants had contributed 2730 accumulated person-years to the analytical dataset. Overall HIV incidence was 5·5 (95% CI 2·7-8·3) per 1000 person-years and incidence was higher among Black participants and those living in the south. Nine participants died during the study. The overall mortality rate was 3·3 (95% CI 1·5-6·3) per 1000 person-years, and the rate was higher among Latinx participants. Identical predictors of HIV seroconversion and death included residence in southern cities, sexual partnerships with cisgender men, and use of stimulants. Participation in the digital cohort and seeking care for gender transition were inversely associated with both outcomes. INTERPRETATION: As HIV research and interventions are increasingly delivered online, differences by mode highlight the need for continued community and location-based efforts to reach the most marginalised transgender women. Our findings underscore community calls for interventions that address social and structural contexts that affect survival and other health concerns alongside HIV prevention. FUNDING: National Institutes of Health. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Characterizing Arrest and Incarceration in a Prospective Cohort of Transgender Women.

This study characterized arrest, incarceration, and risk factors for incident incarceration among transgender women (TW) in the northeastern and southern United States. During semiannual study visits over 24 months in a multicenter cohort study, TW completed HIV testing and self-administered surveys. In total, 1571 TW completed baseline survey; 1,312 HIV-negative TW enrolled in the cohort and contributed 2134.3 person-years to the analysis. At baseline, 37% had been arrested and 21% had been incarcerated. Incident incarceration was 23.4 per 1,000 person-years (95% confidence interval [CI]: 16.9-29.9). Sex work was significantly associated with baseline and incident incarceration (p < .01). A history of incarceration at enrollment was the strongest predictor of incident incarceration (adjusted odds ratio [aOR] 6.99; 95% CI: 3.43-14.24). Living in the South (aOR 2.69, 95% CI: 1.22-5.93), income below the federal poverty level (aOR 2.65 95% CI: 3.43-14.24), and having a recent partner who had been incarcerated (aOR 2.62, 95% CI: 1.20-5.69) also increased the odds of incident incarceration in multivariable modeling. Structural interventions to reduce poverty and decriminalize sex work have the potential to reduce incarceration rates among TW.

Prevention-effective adherence trajectories among transgender women indicated for PrEP in the United States: a prospective cohort study.

PURPOSE: Adherence to pre-exposure prophylaxis (PrEP) during periods of PrEP-indication (i.e., prevention-effective adherence) is critical for preventing HIV. We sought to describe factors associated with prevention-effective adherence trajectories among transgender women (TW) to inform PrEP implementation strategies. METHODS: Using data from The LITE American Cohort (n = 728), we performed group-based multi-trajectory modeling (GBMTM) to identify clusters of TW with similar trajectories of PrEP adherence and indication, and sociodemographic, biobehavioral, and structural correlates of each trajectory. RESULTS: We identified five trajectories: (1) consistent indication/no PrEP (15.3%), (2) initial indication/no PrEP (47.1%), (3) declining indication/discontinued PrEP (9.5%), (4) consistent indication/PrEP adherent (18.5%), and (5) increasing indication/initiated PrEP (9.6%). TW diagnosed with an STI were more likely to follow a consistent indication/no PrEP trajectory compared to consistent indication/PrEP adherent trajectory (adjusted Relative Risk Ratio [aRRR], 2.54; 95% confidence interval [CI], 1.16-5.57). TW who experienced homelessness were more likely to follow PrEP discontinuation and initiation trajectories relative to PrEP adherence (aRRR, 2.71; 95% CI, 1.10-6.70 and 2.83; 95% CI, 1.13-7.05, respectively). CONCLUSIONS: Over a quarter of TW followed trajectories suggestive of prevention-effective adherence, while 15% did not initiate PrEP despite consistent indication. Findings highlight missed opportunities for PrEP engagement at STI diagnosis and suggest structural interventions addressing housing instability may improve prevention-effective adherence among TW.

Perceived HIV Acquisition Risk and Low Uptake of PrEP Among a Cohort of Transgender Women With PrEP Indication in the Eastern and Southern United States.

INTRODUCTION: Preexposure prophylaxis (PrEP) is effective in preventing HIV among adherent users. However, PrEP uptake among transgender women is low, and current prescribing guidelines from the Centers for Disease Control and Prevention (CDC) are not specific to transgender women. Self-perceived risk of HIV among those who are PrEP-indicated is not well understood. METHODS: This cross-sectional analysis included 1293 transgender women screened at baseline from March 2018 to May 2020 for a multisite, prospective cohort study. We compared the prevalence of PrEP indication using current CDC prescribing criteria versus transgender women-specific criteria developed by study investigators with community input. We identified factors associated with study-specific PrEP indication and factors associated with self-perceived low to no HIV risk among those who were PrEP-indicated. We also calculated descriptive statistics to depict the PrEP care continuum. RESULTS: PrEP indication prevalence using transgender women-specific criteria was 47% (611), 155 more than who were identified using the CDC criteria. Eighty-three percent were aware of PrEP, among whom 38% had ever used PrEP. Among PrEP ever users, 63% were using PrEP at the time of the study. There were 66% of current PrEP users who reported 100% adherence within the previous 7 days. Among those who were PrEP-indicated, 13% were using and adherent to PrEP at the time of the study. More than half (55%) of PrEP-indicated participants had low or no self-perceived HIV risk. CONCLUSIONS: These findings suggest that further guidance is needed for health care providers in prescribing PrEP to transgender women. Greater uptake and adherence are also needed for optimal effectiveness.

Transgender-Competent Health Care: Lessons from the Community.

OBJECTIVES: Transgender (trans) individuals experience high discrimination levels when accessing medical and mental health care, resulting in poorer health outcomes compared with the general population and other minority populations. A community-based research design was used to elicit direct input from the trans community about critical trans-knowledgeable care components to address these disparities. The data collection included several focus groups with individuals recruited from the trans community. The information from this research guided the opening of the Gender Center, a centralized, multidisciplinary center of care for trans individuals within an urban safety-net hospital in Atlanta, Georgia. METHODS: The research team conducted five focus groups with 27 self-identified trans individuals between December 2016 and April 2017. Focus groups solicited the negative and positive experiences of trans individuals in the healthcare system and sought input about how best to serve this population. RESULTS: Analysis was done January through April 2020. Focus group participants identified financial difficulties, lack of insurance coverage, being underinsured, discrimination within the healthcare system and from providers, and a shortage of trans-competent providers as the most significant barriers to care. Participants emphasized the need to pay attention to creating a welcoming clinic environment, including trans-positive signage, and integrating trans staff members into the care team. CONCLUSIONS: This study demonstrates the importance of community-based research in addressing health disparities for trans people. It also offers insight into the unmet healthcare needs of the trans community, describes typical healthcare-related experiences of trans individuals, and identifies critical elements for providing high-quality trans-appropriate health care.

Digital Epidemiologic Research on Multilevel Risks for HIV Acquisition and Other Health Outcomes Among Transgender Women in Eastern and Southern United States: Protocol for an Online Cohort.

BACKGROUND: The HIV epidemic disproportionately impacts transgender women in the United States. Cohort studies identify unique risks for affected populations, but use of facility-based methods may bias findings towards individuals living in research catchment areas, more engaged in health services, or, in the case of transgender populations, those who are open about their transgender identity. Digital clinical trials and other online research methods are increasingly common, providing opportunity to reach those not commonly engaged in research. Simultaneously, there is a need to understand potential biases associated with digital research, how these methods perform, and whether they are accepted across populations. OBJECTIVE: This study aims to assess the feasibility of developing and implementing an online cohort of transgender women to assess risks for HIV acquisition and other health experiences. Further, this study aims to evaluate how an online cohort compares to a site-based, technology-enhanced cohort for epidemiologic research. The overarching goal is to estimate incidence of HIV and other health outcomes among transgender women in eastern and southern United States. METHODS: This substudy is part of a larger multisite prospective cohort (LITE) conducted among transgender women, which also includes a site-based, technology-enhanced cohort in 6 eastern and southern US cities. The online cohort was launched to enroll and follow participants across 72 cities in the same region and with similar demographic characteristics as the site-based cohort. Participants are followed for 24 months. Adult transgender women are recruited via convenience sampling (eg, peer referrals, social media, and dating apps). Participants reporting negative or unknown HIV status are enrolled in a baseline study visit, complete a sociobehavioral survey, and provide oral fluid specimens to test for HIV. Participants not living with HIV (lab-confirmed) at baseline are offered enrollment into the cohort; follow-up assessments occur every 6 months. RESULTS: Enrollment into the online cohort launched in January 2019. Active recruitment stopped in May 2019, and enrollment officially closed in August 2020. A total of 580 participants enrolled into and are followed in the cohort. A recruitment-enrollment cascade was observed across screening, consent, and completion of study activities. Implementation experiences with HIV test kits highlight the need for heavy staff engagement to support participant engagement, visit completion, and retention, even with automated digital procedures. CONCLUSIONS: This study is responsive to increasing research interest in digital observational and intervention research, particularly for populations who are most affected by the HIV epidemic and for those who may otherwise not participate in person. The progression across stages of the recruitment-enrollment cascade provides useful insight for implementation of cohort studies in the online environment. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29152.

Primary Care in Transgender Persons.

The preventive health care needs of transgender persons are nearly identical to the rest of the population. Special consideration should be given, however, to the impact of gender-affirming hormone regimens and surgical care on preventive screenings. Providers should integrate a more comprehensive view of health when caring for transgender persons and address the impact of social determinants and other barriers to accessing affirming, inclusive health care. In individual interactions, providers must consider the unique impact that a gender identity and expression different from the assigned gender at birth affects patient-provider interactions, including the history, physical examination, and diagnostic testing.