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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.
This study aims to investigate the rate and correlates of HIV acquisition and other health outcomes among TW in eastern and southern United States.
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.
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.
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.
DERR1-10.2196/14704
Transgender women (TW) are one of the populations most affected by the HIV epidemic in the United States and internationally. A recent systematic review of global health burden in transgender populations further situates the HIV epidemic alongside other health conditions disproportionately facing TW [
Disparities in HIV prevalence exist across races and ethnicity [
Promising empowerment-based and counseling interventions have demonstrated reductions in HIV risk behaviors among TW and their partners [
Several challenges have affected the study of HIV among TW in the United States. First, the lack of transspecific marketing, misgendering during research (referring to TW participant with incorrect names/pronouns), and inclusion of TW among other key populations, such as men who have sex with men, have left a legacy of wariness and hesitation among TW as it relates to participation in HIV research. Despite historical participation in HIV research, TW participants have reported feeling that the successes of these efforts did not result in benefits for the transgender community and that HIV research was often neither specific nor acceptable to TW. Moreover, TW participants have expressed a need for research on other health priorities [
The objective of the American Cohort to Study HIV Acquisition among TW in High-Risk Areas—known locally and by participants as
This is a multiple principal investigator (PI) study led by faculty from Johns Hopkins University (JHU; PI: Wirtz) and Boston Children’s Hospital (BCH), Harvard University (PI: Reisner). The study is supported by leading research institutions, spanning eastern and southern United States, including the following: JHU, Baltimore, Maryland; BCH, Harvard University, and The Fenway Institute at Fenway Health, Boston, Massachusetts; Callen-Lorde, New York City, New York; Emory University and Grady Memorial Hospital, Atlanta, Georgia; University of Miami, Miami, Florida; and Whitman-Walker Health, Washington, DC. The coinvestigators in this team specialize in HIV epidemiology among key populations, transgender health and clinical care, sociobehavioral sciences, management and analysis of longitudinal cohorts, and cross-sectional incidence estimation and laboratory methods. All partner organizations are affiliated with or are themselves clinical sites serving TW, and they have established strong relationships with local community-based organizations that specifically offer services for TW. These relationships continue to be nurtured to ensure the study is acceptable to the transgender community and is consistent with TW’s preferences in terms of study content, as well as to obtain valuable feedback on the study, which can support both recruitment and retention of study participants.
A virtual community advisory board (CAB) has been formed to facilitate research by serving as a mechanism for community consultation, and it will be engaged through every phase of the research activities. The CAB serves as a working partner and provides guidance to the research activities and consent processes; discusses concerns and protection of the community; and publicizes research activities, ancillary services, and results to the wider TW community [
This study draws on the
This study focuses on the recruitment and development of an HIV-uninfected cohort as well as a cross-sectional HIV-infected comparison group. (Note: we recognize and prefer to refer to this group as “TW who are not living with HIV” to minimize stigmatization; however, for the purposes of this technical report, we utilize the term “HIV-uninfected” to refer to the diagnosis associated with study screening criteria.) TW, regardless of HIV status, are recruited via technology-based and nontechnology-based recruitment methods (
HIV-uninfected TW are followed for a minimum of 24 months to estimate HIV incidence, trends, and risk factors for HIV acquisition (
Study flow diagram. TW: transgender women.
The overall study sample, inclusive of formative research, baseline, and cohort participants, is comprised of TW adults, aged ≥18 years, assigned male sex at birth but identifying as women or along the transfeminine spectrum. Gender identity is verified during enrollment by using the recommended 2-step method, which measures sex assigned at birth (step 1) and current gender identity (step 2) [
Cohort enrollment eligibility is determined during the baseline study visit. Eligibility includes a negative baseline HIV test result and at least one of the following risk factors for HIV acquisition (as HIV incidence is the primary outcome of this study): (1) aged 18 to 24 years; (2) screens positive for alcohol use disorder; (3) reports engaging in condomless anal and/or vaginal sex in the previous 12 months; (4) reports lifetime history of sex work; (5) reports unstable housing in the previous 12 months; (6) reports sharing needles to inject hormones, silicone, and/or drugs; (7) screens positive for drug use disorder; (8) reports a lifetime history of injection drug use; (9) reports a lifetime history of incarceration; (10) reports STI diagnosis in previous 3 months; (11) has a positive STI diagnosis at baseline; or (12) reports current or recent (last 12 months) PrEP use. Participants currently enrolled in an HIV prevention clinical trial are excluded.
Generalizability of study results is optimized using multiple study sites across eastern and southern United States. All 6 metropolitan areas are diverse racially, ethnically, and culturally; it is anticipated that the final study sample will be equally diverse, given the team’s past and ongoing research experience and the composition of TW served in clinical care services across sites. Findings may be less generalizable to rural areas; however, there is little known about the number of TW living in rural areas, and the use of online recruitment methods may facilitate participation of those living in more suburban and rural areas surrounding select metropolitan sites. Finally, the minimal use of facility-based data collection efforts during follow-up may help to protect against the Hawthorne effect that may compromise generalizability [
Formative, qualitative research was conducted between August 2017 and January 2018 with members of the TW population to inform recruitment, marketing, and app development. Qualitative research utilized computer-mediated communication (CMC; “Web-based focus groups”) with focus groups comprising participants from across all 6 sites [
Focus groups comprised 5 to 10 TW participants who met via video/teleconference at a mutually agreed upon time. Focus group participants were recruited using the same methods utilized to accrue the cohort and cross-sectional samples (see the Recruitment section), and maximum variation sampling was utilized to enroll participants across a wide range of race, ethnicity, age, geographic residence, and gender transition. Candidate participants were screened for eligibility (see the Sample section), regardless of HIV status, before enrollment, and they had the option to join by audio only, to use video, or to upload a photograph, depending on participant comfort and preference. Discussions were led by a facilitator, utilized audio communication to avoid delays associated with typed CMC, and followed best practices set forth for CMC qualitative research [
Qualitative research was led by investigators from JHU and BCH (Wirtz and Reisner) using standardized methods for qualitative research with key populations [
Study recruitment utilizes a mixed format of technology- and nontechnology-infused recruitment methods. Technology-infused recruitment methods include the use of geosocial networking (GSN) apps frequented by TW, such as Grindr, Black Gay Chat, and Tinder, as well as social media, including Facebook and Reddit, all of which have been successfully used to recruit other populations [
Nontechnology-based recruitment methods include peer referrals and clinic-based referrals (excluding HIV-related services) as well as venue-based recruitment from gender-affirming community events. We used nontechnology-based methods in addition to technology-infused methods, given past research that showed that despite Web-based outreach, only 21% of transgender participants learned of the study via the internet, with the remainder recruited by a peer or support group [
Conferences include but are not limited to the following: First Event, Boston [
Participants are directed from study fliers, SMS text messages, or Web-based advertisements to the study Web page [
Electronic study flier.
All TW who are recruited via the above-mentioned methods and meet eligibility criteria, regardless of HIV status, are asked to participate in a baseline survey, HIV and STI testing, and biospecimen collection. HIV-uninfected TW who meet cohort eligibility criteria are enrolled in the prospective cohort. TW who are recruited but are ineligible for the cohort on the basis of HIV infection are enrolled in a comparison cross-sectional sample and complete the same baseline survey and laboratory testing as the HIV-uninfected cohort.
Each cohort participant is followed for a minimum of 24 months (the duration anticipated for the funding duration, pending grant renewal). Survey and HIV self-testing results are collected from cohort participants every 3 months using a multimodal approach in which facility-based participation is required for baseline visit and 6-, 12-, and 24-month visits, whereas the rest are optional Web-based or facility-based visits (
Every 3 months, surveys will rotate length and format to maintain participant interest, although all surveys will utilize the same core measures selected from the baseline survey to ensure consistency across data collection visits. The app allows participants to report their HIV self-testing results and upload a photo for validation of results.
Participants who experience HIV seroconversion during the study are asked to complete a facility-based visit for confirmation of HIV status (if HIV infection was identified during a Web-based visit) and referral. These participants are offered an additional follow-up visit 3 months after identification of seroconversion to assess uptake of referrals and engagement in the HIVCC (
Leading Innovation for Transgender Women’s Health and Empowerment study app: (a) home screen, (b) study timeline, and (c) access to survey and entry page for home HIV self-test results.
Baseline (Aims 1 and 2) and longitudinal surveys (Aims 3 and 4) are informed by the situated vulnerabilities framework [
All surveys, including facility-based and Web-based, are self-administered. We adapted the Rapid Estimate of Adult Literacy in Medicine – Revised, a brief literacy screening instrument used to assess an adult’s ability to read common medical words, to include terms relevant to TW that are included in the survey (eg, pill, hormones, augmentation, and hepatitis) [
Individual-level measures collect self-reported data on demographics, including zip code of residence, age, race, ethnicity, education, employment status, health insurance, housing, mobility, and history of detention/incarceration; gender affirmation surgery, care, and exogenous hormone use, including age of initiation, based on the US TransPop Survey [
Interpersonal measures include sexual relationships and behaviors measured via an adapted version of the AIDS-Risk Behavior Assessment [
Structural-level measures include social marginalization and stigma, focusing on experiences of enacted and anticipated discrimination, were adapted from the Intersectional Discrimination Scale [
All HIV rapid testing is conducted following completion of the survey. HIV self-testing is performed by baseline participants including, for confirmation purposes, those who report known HIV infection. Participants self-administer the OraQuick self-test (OraSure Technologies) in the study facility during the baseline visit with support from trained study staff. This provides an opportunity for staff to train participants and answer any questions on the use of HIV self-test kits. HIV test results are available within 20 min. All participants with a positive HIV self-test undergo confirmatory testing according to CDC recommendations [
The HIV self-test is used for every 3-month visit (facility-based or Web-based) by cohort participants to support measurement of the primary outcome of interest (seroconversion). Participants completing Web-based study visits are asked to use the study app (
The oral point-of-care HIV test, OraQuick, was approved for self-testing use in the United States by the US Food and Drug Administration in 2012 [
Blood samples are collected at baseline and at 12 and 24 months. Plasma are collected and shipped to JHU to identify individuals with recent infection and estimate incidence at baseline by using a multiassay algorithm [
Self-collected specimens to test for STIs are collected from all participants at baseline and at 12- and 24-month visits, including among HIV-infected baseline and HIV-uninfected cohort participants. Urine samples as well as swabs collected at anorectal and vaginal (for those with vaginoplasty) sites will be self-collected to measure presence of gonorrhea and chlamydia infection. Serum treponemal syphilis testing and rapid plasma reagin (RPR) testing with quantitative RPR titers are used to test for syphilis infection, per local protocols. STI testing is conducted locally at facility-based visits. These STI tests serve as a biologic proxy measure for HIV risk.
HIV testing component of the study app: (a) HIV test timer, (b) HIV test results entry, and (c) photo upload for HIV test validation.
Aim 1 focuses on the efficiencies of recruitment methods. Data on the number of banner ads and postings, impressions (number of online views), and click throughs (number of times the ad was clicked) and data on the number of visits to the study website will be collected for all technology-infused recruitment. For recruitment from gender-affirming events, the number of events, number of participants at each event, and number of candidates accessing study information will be collected. For peer referral, information on the number of unique coupons provided to each participant, number of declined coupons, and number of unique coupons returned to the study staff will be collected. For clinic-based referral, the number of unique TW clients utilizing the clinic during the recruitment period and number of referrals or fliers distributed will be collected. For all recruitment methods, time from recruitment initiation to enrollment, costs associated with recruitment, the number of scheduled enrollment appointments, and the numbers of eligible participants (by HIV status) will be collected by recruitment method. Baseline survey participants will be asked to report how they learned about the study.
Before study implementation, a study manual of procedures was developed, which included the full study protocol as well as study background, design, organizations, recruitment techniques, informed consent, clinical procedures, participant safety, instructions for entering data and using tablets, follow-up procedures, and study definitions. The manual of procedures was then adapted to each site for additional details related to unique aspects of the facility where research is conducted. Updates and clarifications are made as necessary over the course of the project, with revisions available to all staff. All staff are required to undergo training on the overall research objectives and protocol, transgender health, and HIV, along with human subjects training. Clinical staff are required to complete additional training on clinical procedures, confidentiality and privacy, and Good Clinical Practice. Refresher training is scheduled on an annual basis. Weekly calls are held with SCs at each site to discuss adherence to the study protocol, enrollment progress, and experiences with retention.
To ensure consistency in the survey data collection and minimize social desirability bias, we use a computer-assisted self-interview methodology, which includes self-administered tablet-based surveys during facility-based visits and self-administered app-based or Web-based surveys during Web-based study visits. The use of the self-administered tablet-based survey at the facility-based baseline visit allows participants to become accustomed to the Web-based survey and ask for assistance from the study staff. The survey instruments were pilot tested before implementation, and logic checks and skip patterns are built into the program to minimize errors in data capture. Security features of the Web-based and app-based survey allow for data to be saved regularly as participants advance through the survey questions, preventing unintentional loss of data should there be a loss of internet connectivity. Data are reviewed weekly to check for consistency in the data capture processes and assess missingness of data.
Cross-sectional and cohort participants are tracked using a Web-based, Health Insurance Portability and Accountability Act–compliant system hosted by JHU central information technology which allows for facility-based data collection and participant tracking over the course of the study (
Participant database (note: image is a development interface and displays test subjects, not actual participant data).
The Web-based tracking system is customized and configured by the study team to fit the study protocol. Each site has role-based and site-based access to their data, with JHU having full administrative access to all data. It has also been expanded to provide the additional cohort participant app, with an optional URL platform for nonsmartphone users. At enrollment, a unique identifier is generated for participants to log in and access the app and associated surveys. To assist with the recall of the identifier, cohort participants are provided with a study gift (eg, cellphone cardholder) with a study card that includes their study identifier. SCs assist cohort participants with download and installation of the app during enrollment. Participants who encounter problems with subsequent installation (if phone is replaced) or log-in are encouraged to call the study telephone number for support. The participant app is locked on the device once installed, and it requires the entry of the assigned study ID for it to be accessed. The app is Global Positioning System (GPS) enabled, although participants may opt out, to allow for measurement of participant mobility over the duration of the study. The tracking system issues automated push notifications and SMS text messages to the participants’ device for follow-up visit reminders.
All data collected by the tracking system and participant app are encrypted in transit from the device to the server. All the identifying information collected from participants is stored encrypted within the database using the AES 256 bit protocol. Only the research staff requiring access to identifying information for retention purposes has access to protected health information through the tracking system.
Meticulous tracking and retention procedures increase the likelihood that attrition is random and not systematic during study implementation. We use tracking and retention procedures that were proven effective in previous studies. The SC at each site devotes at least 50% time to recruiting and tracking subjects. The SC and other research staff collect and regularly update extensive email/phone/social media contacts, as well as the addresses and contact information of the 3 people that participants believe could help us locate them and will telephone/email/text participants to remind them of their appointment. Automated study visit reminders are also built into the participant tracking system and study app.
Culturally appropriate stepped financial incentives are also provided at each follow-up to encourage continued participation. Depending on the site, additional nonmonetary strategies to improve retention include the following: (1) an anonymous raffle for study participation, (2) provision of links to other non-HIV gender-affirming care and services available during facility-based visits and on the study website and app, (3) a Facebook page on which participants can communicate with each other and staff and post events, and (4) retention events focused on providing non-HIV services of interest (eg, legal name and gender-marker change workshops for identification documents, spa days, and other social events). Retention events are typically held within the community to keep participants engaged in the project.
Facilities provide a range of times of day and days of the week for participants to come to their assessment visits, including evening hours and weekends to support participation by individuals who work or are in school full time. Clinical partners also have excellent reputations within their communities, and they are known for being nonstigmatizing and ensuring privacy and confidentiality, which assists with retention. We also have an extensive network of transgender-focused organizations and clinical care providers in each of our partnering metropolitan areas who serve as referral centers for health needs. Finally, we endeavor to hire study staff who are from the TW or lesbian, gay, bisexual, and transgender community and who have nursing or public health experience, to ensure cultural competence and optimize acceptability of the study.
Study retention is operationally defined as not missing more than 3 consecutive study visits. After 2 missed visits, SCs initiate the retention protocol to track participants through individual and friend/family contacts and calls to local facilities to identify potential incarceration. Participants who express a desire to prematurely exit the study are asked to complete a participant withdrawal questionnaire (on the Web, by phone, or in person) to assess basic characteristics at study exit (eg, HIV status and PrEP use), reason for withdrawal, and whether additional referrals are needed. The study team assesses whether the reason for withdrawal can be addressed, and then the study team will offer resolution, within the limits of the protocol, to the participant. Cohort participants who are lost to follow-up or who have previously withdrawn and request to reenter the study are screened and reassessed for eligibility, and if the timeline allows, they are administratively considered for reenrollment.
We anticipate that 1750 individuals will be screened (approximately 350 per city) from years 1 to 2. Assuming 10% of those screened are ineligible and have an HIV prevalence of 30%, TW enrolled at the end of Year 2 will include 1100 HIV-uninfected TW (approximately 220 per city) and 475 HIV-infected TW in the baseline, cross-sectional comparison group.
We conservatively estimated that 700 pys of follow-up accumulated from Years 1 to 2 during enrollment. Incorporating a loss of 15% of follow-up time per year (from a combination of loss to follow-up and mortality), we estimate that we will accumulate 935 pys, 795 pys, and 676 pys in Years 3, 4, and 5, respectively (>3000 pys total). To compare the incidence of 2 subgroups (eg, incidence by black vs nonblack race), assuming 2-sided test statistics and 5% Type 1 error 80% power, we have sufficient power (80%) to detect public health–relevant differences in HIV incidence by various participant characteristics (
Power to detect public health–relevant differences in HIV incidence by subgroups. py: person years.
HIV incidence in TW is the primary study outcome of interest. With respect to the baseline, cross-sectional incidence estimate, a sample of 1575 individuals at baseline with 30% prevalence and estimated cross-sectional 8% incidence would identify 37 “recently” infected individuals with a 95% CI of 4.7-11.5 using the validated algorithm [
Study attrition is tracked using data visualization techniques, stratifying important metrics over time (such as the number enrolled and proportion lost to follow-up) by site. Monthly updates to these figures will help to detect problems and initiate a timely response to ensure at least 1000 TW are enrolled in the cohort and to reduce loss to follow-up. Statistical analyses of attrition will be conducted, including a comparison of demographic characteristics, social factors, and HIV risk behaviors among those retained versus lost to follow-up. Survival analyses will be used to investigate factors associated with loss to follow-up.
Data management and statistical analysis are led by statisticians and data managers in the John Hopkins Bloomberg School of Public Health (JHSPH) Statistics in Epidemiology (STATEPI) group (which serves the North American AIDS Cohort Collaboration on Research and Design and the Multicenter AIDS Cohort Study / Women’s Interagency HIV Study Combined Cohort Study, which are longitudinal cohorts of adults with, and at-risk for, HIV infection) with oversight by study investigators (ALW, SR, and KNA). Analyses essential to the proposed aims include tracking and investigations into attrition, comparison of HIV-infected and HIV-uninfected TW at baseline, both HIV incidence and time-to-event analyses to better understand drivers of HIV transmission, and serial cross-sectional looks at the HIVPC and HIVCC over calendar time.
Statistical analysis throughout the study addresses the overarching specific aims and hypotheses. Aim 1 analyses focus on exploring optimal recruitment methods and the efficiency of each method. Data visualization techniques are being utilized to compare efficiency of recruitment methods in terms of process measures of time, cost, and response rates. Additional descriptive analyses compare quantitative measures of acceptability and will also assess diversity and potential biases of the samples recruited, in terms of demographics, risk behaviors, and HIV status. Differences are not statistically compared across recruitment methods, given heterogeneity of recruitment methods and process measures.
Aim 2 analyses include descriptive statistics to compare demographic and behavioral risk profiles among HIV-uninfected and HIV-infected baseline participants as well as to assess baseline HIVPC and HIVCC among HIV-uninfected and HIV-infected participants, respectively. Log binomial models (or, when such models fail to converge, we will approximate with Poisson regression models with robust variance) are used to estimate HIV prevalence ratios and 95% CIs for demographic and risk characteristics; subgroup analyses will be conducted, stratified by site. Latent class analysis will be further used to explore profiles of HIV-infected and HIV-uninfected participants at baseline [
Aim 3 analyses will focus on differences in HIV incidence during follow-up (and 95% CIs) among the HIV-uninfected cohort will be estimated using Poisson regression models to investigate important predictors, including (but not limited to) age, race/ethnicity, and geographic location. Observed HIV incidence from the cohort will be compared with baseline cross-sectional incidence to assess for differences in incidence and potential mechanism for such differences (eg, differences in participant profiles and behavioral modification). Time-to-event survival models will be used to estimate the risk of HIV seroconversion for the predictors. A scan statistic will be used with the zip code of residence and GPS data to detect seroconversion event clusters in time or space (or both) for identification of potential microepidemics. The scan statistic is commonly used to identify the most likely cluster location, where a significant
Analyses for Aim 4 will focus on the steps in the HIVPC and HIVCC are investigated among HIV-uninfected and HIV-infected TW, respectively, using a serial cross-sectional approach to determine trends in these important frameworks. To make these estimates most useful for policy and program, the steps are estimated among those under observation in specific calendar years (ie, in 2019, 2020, and 2021).
For analytic refinements, we will make use of modern missing data techniques [
Scientific measurement of HIV infection, as well as gender identity, sexual identity and behavior, and stigma, is inherently sensitive in nature. All study activities are developed with attention to protection of participant privacy and confidentiality and in discussions with the study CAB. All participant study data are retained separately from participant identifiers; only study staff responsible for scheduling or referrals have permissions to access participant identifiers. The electronic data system has been developed with careful attention to security, including password protection and no obvious information that the app is developed for TW or for HIV research. Participants are provided with clear instructions on how to use, discretely store, and report results from the HIV self-test as well as how to contact the study staff in the event of a positive test result. Given concerns of stigma and discrimination, only referrals to clinics or community based organizations that have been vetted and determined to be gender affirming are provided. Finally, the CAB has been consulted throughout all phases of the study to ensure acceptability of methods among the TW community. Study activities follow a single centralized Institutional Review Board (IRB) procedure and have undergone review and approval by the Johns Hopkins School of Medicine IRB. All collaborating organizations and institutions rely on this approval.
Rigor and reproducibility are ensured throughout all phases of the study by the stringent application of the scientific method to minimize bias in design, methodology, analysis, and interpretation of results, and they will follow methods successfully used by
Formative research was conducted between August 2017 and January 2018, and findings have been described elsewhere [
In March 2018, the cohort was launched at the Baltimore and Boston sites, followed by launches of the cohort in the remaining cities in April and May 2018. This staggered approach was established to allow for any troubleshooting of study implementation procedures, the CTMS, and study app before the full launch in other sites as well as for final IRB reliance agreements to be established. As of March 20, 2019, 795 TW were screened and 739 TW were enrolled in and completed the baseline study visit (median age 32 years, interquartile range; IQR 25-42 years). Majority of the participants are racial/ethnic minorities, with 45.1% (333/739) of the participants identifying as black and/or 27.8% (206/739) identifying as Hispanic/Latinx.
Of these baseline participants, 206 (27.8%, 206/739) were found to be living with HIV at baseline and 480 (64.9%) were HIV-uninfected and met behavioral risk criteria and were enrolled in the cohort (cohort median age: 29 years, IQR 24-37 years). This contributed to a total 245.4 pys in the cohort as of March 2019. A total of 17% (126/739) of the baseline participants were identified with lower levels of literacy, requiring interviewer-administered surveys and HIV tests, as well as in-person visits. Other participants have requested in-person visits, reportedly for the purposes of having a safe and private place to participate in study activities, comfort in having a staff member perform or be present for HIV testing, or because the participant wanted to see or spend time with study staff.
Baseline participants have entered the study through a variety of recruitment methods, including peer referral (38.9%, 288/739), referral from a health facility (40.0%, 296/739), referral from a community-based organization (12.0%, 89/739), study flier (10.9%, 81/739), Facebook (7.9%, 59/739), dating apps (4.0%, 30/739), or other websites (4.0%, 30/739), such as Craigslist, Backpage, and Eros. However, study recruitment has progressed overall at a rate lower than expected and with lower proportions recruited online than anticipated. The use of advertising campaigns in dating apps to recruit participants appeared to reach a large number of individuals (1,390,827 impressions and 11,629 clicks on the study website during geotargeted campaigns via 1 dating app), but it resulted in only 24 enrollments to date. This is likely attributable to the fact that TW may use dating apps that are developed for heterosexual populations, as well as people in same sex relationships, with no single app being uniquely for or in high use by TW, thus limiting the number of those who can be reached through advertisements via these apps. Furthermore, challenges in communication with dating app representatives, low transparency and barriers to recruitment data, and cost associated with recruitment via dating apps suggest that these are not efficient methods for recruitment of TW for research. Given these challenges, we have broadened recruitment to advertising campaigns via Facebook, Reddit, and Google Ads, as well as sharing information about the study through media interviews [
This study is responsive to increasing research interest in technology-enhanced methods for cohort research, particularly for hard-to-reach populations. The cohort utilizes innovative methods that harness technology alongside traditional methods and facility-based visits to develop the first multisite US cohort to assess HIV risk among one of the most affected populations. Study findings have important implications for informing future HIV prevention and care research, including identification of optimal recruitment and retention methods, estimating HIV incidence and identifying risk factors for HIV acquisition, and ultimately informing the development of acceptable HIV prevention and care efforts for TW in the United States. Importantly, the diversity of literacy, technology use, and overall socioeconomic situations in this sample of TW highlights the need to balance study rigor with use of flexible methods to ensure that with increasing technology, those living in the most vulnerable contexts are not excluded from research.
Limitations of the study must be recognized. First, the sample size is relatively small compared with other national cohorts that comprise larger, less stigmatized populations. However, the use of multiple partnering sites with strong ties to the TW community, partnership with a CAB, and use of mixed-format recruitment and data collection methods are anticipated to encourage recruitment and retention across sites. As additional funding is identified, new sites and organizational partners may also be added. Although the pooled contribution of cohorts from multiple sites adds strength to the study, pooled results can provide misleading or overly smoothed inferences. Our analytic “best practices” protocol includes examining data for each cohort to understand the magnitude of heterogeneity in estimates. Statistical methods for determining cohort interactions and combining pooled results [
This study establishes a multisite, longitudinal cohort of TW in eastern and southern United States, targeting 6 high-risk metropolitan areas: Baltimore; Washington, DC; Boston; New York City; Atlanta; and Miami, and it is now one of the largest cohorts specifically comprising TW in the United States. The goal is to characterize risk factors for HIV infection, access to biobehavioral HIV prevention methods, and linkage to care for those who HIV seroconvert for the purposes of informing evidence-based and acceptable interventions to reduce HIV incidence for this at-risk population. The cohort will include a racially, ethnically, and culturally diverse sample of TW, supported by technology-based recruitment and retention methods. The study is designed to (1) answer methodologic questions about appropriate and effective recruitment and retention methods for TW, as well as potential biases in these methods; (2) provide HIV incidence estimates and, through the use of both cross-sectional and longitudinal incidence measures, assess potential influences on incidence estimations; (3) identify individual social and structural risk factors for HIV acquisition; and (4) evaluate engagement in the HIVPC and HIVCC among HIV-uninfected and HIV-infected TW. We anticipate that the cohort study will serve as a platform upon which pilot interventions, studies of sexual partners, cohorts of TW youth, additional geospatial and phylogenetic analysis to further contextualize hot spots, mathematical modeling to assess the impact of promising interventions, and analysis of the role of exogenous hormone use in HIV infection can be built. Collectively, these findings will inform optimal components of promising interventions to reduce HIV incidence among TW.
Peer-reviewer report from the National Institutes of Health.
Boston Children’s Hospital
Community Advisory Board
Centers for Disease Control and Prevention
Centers for AIDS Research
computer-mediated communication
Global Positioning System
geosocial networking
HIV/AIDS, Hepatitis, STD, and TB Administration
HIV Care Continuum
HIV Prevention Continuum
interquartile range
Institutional Review Board
John Hopkins Bloomberg School of Public Health
Johns Hopkins University
Leading Innovation in Transgender Health and Empowerment
principal investigator
pre-exposure prophylaxis
person years
respondent-driven sampling
rapid plasma reagin
study coordinator
short message service
Statistics in Epidemiology
sexually transmitted infection
transgender women
The authors would like to express their gratitude to the TW who take part in this study. This study would not be possible without their participation. Research reported in this publication was jointly supported by the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, and the National Institute of Child Health and Human Development of the National Institutes of Health under Award Number UG3AI133669 (ALW and SLR). Research reported in this publication was also supported by HIV/AIDS, Hepatitis, STD, and TB Administration (HAHSTA), Washington DC Department of Health. The LITE study is also appreciative of support from the CFAR at partner institutions, including JHU (P30AI094189), Emory University (P30AI050409), Harvard University (P30AI060354), DC CFAR (AI117970), and the University of Miami (P30AI073961). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or HAHSTA.
The following are members of the collaborative author, American Cohort to Study HIV Acquisition Among TW (LITE): Sari Reisner (multiple PI; Harvard University, BCH); Andrea Wirtz (multiple PI; JHU); Keri Althoff (JHU); Chris Beyrer (JHU); James Case (JHU); Erin Cooney (JHU); Oliver Laeyendecker (JHU); Tonia Poteat (University of North Carolina); Kenneth Mayer (Fenway Health); Asa Radix (Callen-Lorde Community Health Center); Christopher Cannon (Whitman-Walker Health); W David Hardy (Whitman-Walker Health); Jason Schneider (Emory University and Grady Hospital); Sonya Haw (Emory University and Grady Hospital); Allan Rodriguez (University of Miami); Andrew Wawrzyniak (University of Miami); and the LITE CAB, including the following individuals: Jennifer Lopez, Sherri Meeks, Sydney Shackelford, Nala Toussaint, SaVanna Wanzer, and Joseph Zolobczuk, as well as those who have remained anonymous. ALW and SLR developed the study concept; TP, AR, KNA, CC, AW, EC, and KM provided extensive input to the original grant submission and/or the protocol manuscript; ALW wrote the first draft of the manuscript; and all authors reviewed and provided scientific input to the manuscript.
None declared.