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.

Cardiovascular Disease Risk Estimation for Transgender and Gender-Diverse Patients: Cross-Sectional Analysis of Baseline Data From the LITE Plus Cohort Study.

Introduction: Approximately 2% of the U.S. population identifies as transgender, and transgender people experience disproportionate rates of cardiovascular disease mortality. However, widely used cardiovascular disease risk estimators have not been validated in this population. This study sought to determine the impact on statin therapy recommendations using 3 different approaches to operationalizing sex in the American Health Association/American College of Cardiology Pooled Cohort Equation Risk Estimator. Methods: This is a cross-sectional analysis of baseline clinical data from LITE Plus, a prospective cohort study of Black and/or Latina transgender women with HIV. Data were collected from October 2020 to June 2022 and used to calculate Pooled Cohort Equation scores. Results: The 102 participants had a mean age of 43 years. A total of 88% were Black, and 18% were Latina. A total of 79% were taking gender-affirming hormones. The average Pooled Cohort Equation risk score was 6% when sex assigned at birth was used and statins would be recommended for the 31% with Pooled Cohort Equation >7.5%. The average risk score was 4%, and 18% met the criteria for statin initiation when current gender was used; the mean risk score was 5%, and 22% met the criteria for statin initiation when current hormone therapy was used. Conclusions: Average Pooled Cohort Equation risk scores vary substantially depending on the approach to operationalizing the sex variable, suggesting that widely used cardiovascular risk estimators may be unreliable predictors of cardiovascular disease risk in transgender populations. Collection of sex, gender, and hormone use in longitudinal studies of cardiovascular health is needed to address this important limitation of current risk estimators.

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.

HIV awareness and prevention strategies among transgender women in the Eastern and Southern United States: findings from the LITE Study.

INTRODUCTION: Transgender women (TW) experience an increased risk of human immunodeficiency virus (HIV) acquisition. This study identified patterns of HIV awareness and prevention strategies used by TW who were not living with HIV. METHODS: Data were drawn from a baseline survey of the LITE Study, a multi-site cohort of TW in Eastern and Southern United States (March 2018-August 2020). We conducted a latent class analysis to identify classes of HIV awareness and prevention strategies among TW who reported past 12-month sexual activity (N = 958) using 10 variables spanning HIV knowledge, receipt and use of HIV prevention strategies, and sexual practices. Due to differences across the cohort arms, classes were estimated separately for TW enrolled in site-based versus online study arms. We identified demographic characteristics, gender-affirming indicators and HIV vulnerabilities associated with class membership. RESULTS: Four parallel classes emerged: class 1 "limited strategies-less sexually active" (15% and 9%, site-based and online, respectively), class 2 "limited strategies-insertive sex" (16%/36%), class 3 "limited strategies-receptive sex" (33%/37%) and class 4 "multiple strategies-insertive and receptive sex" (36%/18%). Across all classes, condomless sex, pre-exposure prophylaxis (PrEP)/post-exposure prophylaxis (PEP) prevention knowledge and awareness were high but reported PrEP/PEP use was low. Compared with class 1, membership in class 4 was associated with being a person of colour (site-based OR = 2.15, 95% CI = 1.15-4.00, online OR = 4.54, 95% CI = 1.09-18.81) increased odds of self-perceived medium-to-high HIV risk (site-based OR = 4.12, 95% CI = 2.17-7.80, online OR = 11.73, 95% CI = 2.98-46.13), sexually transmitted infections (STI) diagnosis (site-based OR = 6.69, 95% CI = 3.42-13.10, online OR = 8.46, 95% CI = 1.71-41.78), current sex work (site-based OR = 6.49, 95% CI = 2.61-16.11, online OR = 10.25, 95% CI = 1.16-90.60) and 2-4 sexual partners in the last 3 months (site-based OR = 2.61, 95% CI = 1.33-5.13). Class 3, compared with class 1, had increased odds of current sex work partners (site-based OR = 3.09, 95% CI = 1.19-8.07) and of having 2-4 sexual partners in the last 3 months (site-based OR = 3.69, 95% CI = 1.85-7.39). CONCLUSIONS: TW have varied HIV awareness and prevention strategy utilization, with clear gaps in the uptake of prevention strategies. Algorithms derived from latent class membership may be used to tailor HIV prevention interventions for different subgroups and those reached through facility-based or digital methods.

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.

Transgender and Gender Diverse Community Connection, Help-Seeking, and Mental Health Among Black Transgender Women Who Have Survived Violence: A Mixed-Methods Analysis.

Black transgender women are disproportionately affected by violence and poor care-delivery, contributing to poor mental health. Little is known regarding the effect of transgender and gender diverse (TGD) community connection (TCC) on health. This analysis (a) explores relationships between TCC, polyvictimization, and mental health and (b) analyzes how TCC influenced help-seeking following violent experiences among Black transgender women. Mixed-methods data from 19 Black transgender women were analyzed using correlational and thematic content analyses. Findings suggest that TCC is associated with improved help-seeking and mental health among Black transgender women, highlighting a need for longitudinal research to identify approaches for leveraging TCC.

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.

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.

Integrated Assessment of Viral Transcription, Antigen Presentation, and CD8+ T Cell Function Reveals Multiple Limitations of Class I-Selective Histone Deacetylase Inhibitors during HIV-1 Latency Reversal.

Clinical trials investigating histone deacetylase inhibitors (HDACi) to reverse HIV-1 latency aim to expose reservoirs in antiretroviral (ARV)-treated individuals to clearance by immune effectors, yet have not driven measurable reductions in the frequencies of infected cells. We therefore investigated the effects of the class I-selective HDACi nanatinostat and romidepsin on various blocks to latency reversal and elimination, including viral splicing, antigen presentation, and CD8+ T cell function. In ex vivo CD4+ T cells from ARV-suppressed individuals, both HDACi significantly induced viral transcription, but not splicing nor supernatant HIV-1 RNA. In an HIV-1 latency model using autologous CD8+ T cell clones as biosensors of antigen presentation, neither HDACi-treated CD4+ T cell condition induced clone degranulation. Both HDACi also impaired the function of primary CD8+ T cells in viral inhibition assays, with nanatinostat causing less impairment. These findings suggest that spliced or cell-free HIV-1 RNAs are more indicative of antigen expression than unspliced HIV-RNAs and may help to explain the limited abilities of HDACi to generate CD8+ T cell targets in vivoIMPORTANCE Antiretroviral (ARV) drug regimens suppress HIV-1 replication but are unable to cure infection. This leaves people living with HIV-1 burdened by a lifelong commitment to expensive daily medication. Furthermore, it has become clear that ARV therapy does not fully restore health, leaving individuals at elevated risk for cardiovascular disease, certain types of cancers, and neurocognitive disorders, as well as leaving them exposed to stigma. Efforts are therefore under way to develop therapies capable of curing infection. A key focus of these efforts has been on a class of drugs called histone deacetylase inhibitors (HDACi), which have the potential of exposing hidden reservoirs of HIV-1 to elimination by the immune system. Unfortunately, clinical trial results with HDACi have thus far been disappointing. In the current study, we integrate a number of experimental approaches to build a model that provides insights into the limited activity of HDACi in clinical trials and offers direction for future approaches.

American Cohort to Study HIV Acquisition Among Transgender Women in High-Risk Areas (The LITE Study): Protocol for a Multisite Prospective Cohort Study in the Eastern and Southern United States.

BACKGROUND: In the United States, transgender women (TW) are disproportionately burdened by HIV infection. Cohort studies are needed to evaluate factors driving HIV acquisition among TW over time. These will require implementation strategies that are acceptable to the TW community and feasible to implement. OBJECTIVE: This study aims to investigate the rate and correlates of HIV acquisition and other health outcomes among TW in eastern and southern United States. METHODS: LITE is a multisite prospective cohort in 6 eastern and southern US cities, which will be followed across 24 months of technology-enhanced biobehavioral follow-up. Adult TW, regardless of HIV status, are recruited via convenience sampling (eg, peer referrals, social media, and dating apps). Participants are enrolled in a baseline study visit, complete a sociobehavioral survey, and test for HIV and sexually transmitted infections. Participants who are not living with HIV at baseline are offered enrollment into the cohort (N=1100); follow-up assessments occur quarterly. RESULTS: Cohort assembly was informed by synchronous Web-based focus group discussions with TW (n=41) and by continuing engagement with community advisory board members from each site. Enrollment launched in March 2018. The study is underway in the Atlanta; Baltimore; Boston; Miami; New York City; and Washington, DC, metro areas. As of March 2019, 795 TW completed a baseline visit (mean age 35 years). The majority of the participants are racial/ethnic minorities, with 45% of the TW identifying as black and 28% of the TW identifying as Hispanic/Latinx. More than one-quarter (28%) of the TW are living with HIV infection (laboratory-confirmed). Online recruitment methods support engagement with TW, although peer referral and referral through trusted health facilities and organizations remain most effective. CONCLUSIONS: This study is responsive to increasing research interest in technology-enhanced methods for cohort research, particularly for hard-to-reach populations. Importantly, the diversity of literacy, technology use, and overall socioeconomic situations in this sample of TW highlights the need to leverage technology to permit a flexible, adaptive methodology that enhances engagement of potential participants living in marginalized contexts while still ensuring rigorous and sound study design. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14704.

Validation of a Brief Measure of Opioid Dependence: The Rapid Opioid Dependence Screen (RODS).

The Rapid Opioid Dependence Screen (RODS) is an 8-item measure of opioid dependence designed for quick, targeted screening in clinical and research settings. Based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, criteria, the RODS has an average administration of less than 2 minutes and can easily be administered as a stand-alone instrument or as part of a comprehensive interview. This study reports on the initial validation of the RODS among a sample of 97 newly incarcerated, HIV-positive individuals. Using the Mini International Neuropsychiatric Interview as the primary measure of opioid dependence, the RODS showed good-to-strong sensitivity (.97), specificity (.76), positive predictive value (.69), and negative predictive value (.98), while concordance analysis revealed moderate diagnostic agreement (κ = .67). Psychometric properties revealed strong internal consistency (α = .92) and inter-item correlations (.66 to .87).