The US Department of Health and Human Services has proposed an end to the HIV epidemic in the United States by 2030; this will require flexible, yet targeted, strategies that successfully segment people based on age, demographic characteristics, and location. As HIV infection rates continue to fluctuate across communities, a trend has emerged with new HIV infections becoming increasingly concentrated—with cascading effects—among people aged <30 years, from marginalized racial and ethnic groups, and who are sexual and gender minorities [1,2].

Young men who have sex with men (YMSM) account for most new HIV infections each year. Recent data highlight that, in 2018, 21% of new HIV diagnoses were in people aged between 13 and 24 years, of whom 92% reported male-to-male sexual contact as their mode of HIV infection [3]. These numbers are even more alarming among YMSM of color. Of all new HIV cases among African American and Black men, 20% occur in those aged 13 to 24 years, and 39% occur in those aged between 25 and 35 years [4]. Furthermore, although overall infection rates decreased among the general Latino population from 2005 to 2014, new infections among Latino YMSM aged between 13 and 24 years increased by 87% [5]. Although the overall incidence of HIV infection has decreased in the United States, disparities among youth, particularly African American and Black and Latino YMSM, persist [6,7].

The burden of HIV among YMSM is rooted in the interaction of social, economic, and demographic inequities that enhance their risk for HIV. YMSM report more difficulty in accessing health care, anticipated mistreatment from health care providers, and frequent experiences with stigma, which may lead to psychosocial challenges such as increased substance use and involvement in high-risk behaviors [6,8,9]. YMSM of color are especially vulnerable to multiple forms of stigma (eg, discrimination, racism, family rejection, and homophobia) that are influenced by their race, ethnicity, or sexual identity and interact to produce unique HIV risk profiles for individuals [10-12]. For example, African American and Black YMSM report high levels of institutionalized and sexualized racism and discrimination, which puts them at increased risk for internalized homophobia, maladaptive coping, and other mental health issues, which are further associated with illicit drug use and sexual risk taking [13-15]. Among Latino YMSM, who experience great demands to meet traditional gender roles, machismo is associated with elevated rates of unprotected sex [16,17].

Stigma also affects YMSM’s engagement in and adherence to the HIV prevention continuum—by discouraging them from accessing information, preventing them from getting tested, and hindering their access to breakthrough biomedical interventions [18]. For example, uptake of pre-exposure prophylaxis (PrEP), a daily regimen of 2 oral antiretroviral drugs taken as a single pill that has been proven to be up to 97% effective in reducing the risk of acquiring HIV [19], is lowest among youth despite their demonstrated need [6,20]. Compared with men who have sex with men (MSM) in general, YMSM are less aware of their HIV serostatus, less likely to engage in and adhere to antiretroviral therapies (ARTs), and less likely to use PrEP; uptake is at 9.4% among YMSM and 19.9% for all MSM [21,22].

Furthermore, African American and Latino YMSM are 2 subgroups with the least likelihood of engaging in PrEP [23,24], suggesting that the efficacy of current HIV prevention efforts is reduced in YMSM who are burdened by multiple forms of co-occurring stigma [7,18].

Compared with YMSM, transgender and nonbinary youth of color, or transgender and gender minority youth (TGMY), experience high levels of multiple forms of stigma (eg, low income, isolation, safety concerns, and discrimination) that place them at great risk for poor mental health, depression, suicidality (ie, ideation, plan, and attempt), physical and psychological violence, substance use, and HIV acquisition [7,25-29].

TGMY have varied gender identities that differ from their sex assigned at birth [30,31], and although the terminology used to describe TGMY communities is constantly evolving, TGMY generally includes youth who identify with a gender different from the sex assigned to them at birth or youth who express their gender identity in a way that diverges from the traditional male-female gender binary, such as genderqueer, gender-fluid, or nonbinary. TGMY communities also include sexual, racial, and ethnic minority youth.

Data around TGMY’s HIV risk and health profiles remain limited, especially for young transgender men and nonbinary youth. This lack of information is reflected by few existing resources, which hinders TGMY’s ability to negotiate safe sexual interactions with partners and communicate effectively with providers [7,32]. Health care providers also report a lack of preparation to care for TGMY, and many institutions lack policies and routine practices to support the needs of gender minority patients [33,34]. In addition, in some nonprobability community samples of young transgender women, 25% to 43% of transgender women reported experiencing unstable housing or homelessness [35,36], 67% reported engaging in sex work [35], and 31% reported experiencing sexual violence in the past 12 months [37]. TGMY are 3 times more likely than YMSM to experience workplace discrimination [38], with traumatic experiences and suicidality being more prevalent among nonbinary and gender-nonconforming minority youth [27].

Furthermore, transgender adolescents are more likely to have ever had sex and less likely to have used a condom during their previous sexual experience than their cisgender peers [39]. TGMY are more likely to report first sexual intercourse at or before the age of 13 years, intercourse with ≥4 partners, substance use before sexual activity, and unprotected sex during the previous encounter [40]. Among transgender women and men who seroconverted between 2009 and 2014, 36% of transgender women and 23% of transgender men were aged between 13 and 24 years [26]. Taken together, these findings indicate that TGMY are more at risk for HIV infection than cisgender youth, including YMSM [40], and underlines the need for contextual understanding of the multiple forms of stigma faced by TGMY in relation to their HIV risk [32].

Given the need to further understand the unique experiences of African American and Black and Latino YMSM and TGMY, we propose to build on existing studies and longitudinally examine how (1) YMSM and TGMY experience various forms of intersectional identities and stigma over time, as they age; (2) stigma and intersectionality drive risk for substance use, sexually transmitted infection (STI), HIV infection, and mental health and psychosocial disorders; and (3) stigma and intersectionality serve as barriers to engagement in the HIV prevention and care continua, with particular attention to PrEP and ART uptake and adherence. By examining these aims, we hope to identify when and for whom to target interventions aimed at specific determinants and mechanisms of health. This paper describes the protocol for the renewal of our Healthy Young Men’s (HYM) Cohort Study to continue our research with the HYM and TRUTH: A Transgender Youth of Color Study (TRUTH) Cohorts.

In 2015, Children’s Hospital Los Angeles was awarded a grant (U01DA036926) from the National Institute on Drug Abuse (NIDA) to recruit and longitudinally track a cohort of African American and Black and Latino YMSM to better understand how to engage this high-risk population in the HIV prevention and care continuum. With this grant, we launched the HYM Cohort Study and, in 2016, enrolled 448 African American and Black and Latino YMSM and collected 8 waves of data through assessments administered every 6 months from 2016 to 2020. In 2018, we received an administrative supplement to recruit and collect 2 waves of data for a new cohort of transgender, nonbinary, and gender-nonconforming youth. From this, we launched the substudy, TRUTH, which recruited 108 participants via social media and community referrals and collected 3 waves of data through assessments administered every 6 months from 2018 to 2020; study assessments for both HYM and TRUTH included survey data collection, STI and HIV testing, and drug screening every 6 months.

In 2020, our renewal application was awarded. For this next funding cycle (2020-2025), our study will focus on HIV risk and transmission for YMSM and TGMY through the lens of intersecting stigmatized identities, including sexual identity, gender identity, race, ethnicity, immigration status, financial hardship, HIV+ status, mental health, psychiatric disorders, and sex work or transactional sex.

Results from the first 4 years of data collection suggest a complicated story that is rooted in minority stress, stigma, and intersectionality of identity and stigma [15]. YMSM and TGMY are located at the intersection of multiple identities, each of which has unique forms of stigma; thus, applying concepts of intersectional identity and stigma to observational studies may provide novel insights into facilitators of and barriers to HIV care.

This study has been reviewed and approved by the institutional review board (IRB) at Children’s Hospital Los Angeles (CHLA-14-00279). Participants were initially recruited from the previous iterations of HYM and TRUTH studies [48]; they were screened for eligibility to continue in the study, and if eligible, they were invited to participate in the study as further described in the following sections. All participants provided written informed consent during a web-based reconsenting visit and were informed that continuing participation in the study is voluntary and that they could exit at any time.

We will use a longitudinal design with data collection occurring every 6 months to examine changes over time with respect to intersectional identities and relationship with HIV and STIs, drug use, and mental health risk. Data collection will include a quantitative survey; qualitative interviews; and collection of biological specimens for rapid HIV tests and STI tests (ie, rectal and throat swabs), urine for recent substance use, blood for syphilis testing, and blood samples for later analysis. HYM and TRUTH Cohort Study will continue to conduct triangulated analysis of quantitative, qualitative, and biological measures (ie, drug use, HIV and STI testing, and adherence to ART for participants who are HIV+) at baseline and every 6 months for a total of 8 waves of data collection scheduled to occur from fall of 2021 to summer of 2025. Furthermore, qualitative substudies will be integrated into the study using the time line follow-back approach on an as-needed basis to further contextualize our quantitative findings.

In 2016, we recruited a cohort of 448 (n=397, 88.6% HIV– and n=51, 11.4% HIV+) YMSM into the HYM Cohort Study; the sample comprised African American and Black and Latino YMSM who are HIV+ or at high risk for HIV acquisition; 58.9% (264/448) self-identified as Latino, 20.9% (94/448) as African American, and 20.1% (90/448) as multiracial. Mean age at recruitment was 22.3 (SD 2.02) years. We will continue data collection with this existing cohort. To do this, we contacted participants, informed them of the study renewal, and invited them to reconsent via an IRB-approved web-based video conferencing.

Similarly, data collection will continue with the current TRUTH cohort (N=105) using the approach described previously. In addition, we will recruit 250 new TGMY (eg, approximately n=100, 40% transgender women; n=100, 40% transgender men; and n=50, 20% gender-nonconforming and nonbinary youth) to allow for additional data collection and analysis with this understudied community. We are particularly interested in recruiting participants who are substance users (especially methamphetamines and opioids) or living with HIV. Eligibility criteria for additional study recruitment of the HYM and TRUTH Study Cohorts are as follows: (1) aged between 20 and 26 years; (2) self-identify as Black or African American, Latino or Latinx, or a mixed-race individual; (3) self-identify as a cisgender man, transgender individual, or nonbinary individual; (4) lived in the Los Angeles metropolitan area; and (5) have had sex with a penis in the past 12 months.

YMSM and TGMY will be excluded from the study if they (1) do not meet the inclusion criteria, (2) appear to be under the influence of drugs or alcohol during their study visit (research staff is trained to identify objective signs of intoxication), (3) are not able to commit to the study through completion, or (4) are not fluent in English or Spanish as determined during screening and informed consent process.

Recruitment resumed in October 2021. We continue to recruit participants via referrals from community partners and through social media platforms such as Facebook, Instagram, and Grindr [48].

This study will continue using the tracking and retention procedures previously used, including incentivized monthly check-ins with participants to identify changes in contact information [48]. Participants receive US $5 per month for reaching out to study staff and alerting them to any changes in contact information. Periodic newsletters are sent to participants to remind them about study-related events, and social events maintain participant engagement throughout the study.

Community Advisory Boards (CABs) continue to be critical partners in our study conducted with YMSM and TGMY. We will continue to convene a CAB and Youth CAB (YCAB) to inform all aspects of the HYM and TRUTH Cohort Study. CAB and YCAB members include policy makers, HIV prevention and care service providers, advocates, and members of our target population (eg, racially and ethnically diverse YMSM and TGMY). Our CAB and YCAB have been invaluable in helping us to develop or refine our data collection instruments, methods, sample selection and retention efforts; identify resources for participants; interpret study findings; and disseminate findings to local organizations and policy makers. Going forward, we have adapted our CAB and YCAB to include great representation for our study population of YMSM and TGMY; we have confirmed a total of 18 CAB members, who meet quarterly.

Univariate statistics will be used to examine and chart the characteristics of the cohorts and subgroups within them (eg, race and ethnicity subgroups and gender identity subgroups), including demographics, STI and HIV incidence by pathogen and anatomical site, substance use from self-report and urine samples, use of HIV testing and prevention services, health care use and engagement, use of biomedical HIV prevention (eg, PrEP) for those who are HIV–, and adherence to ART for those who are HIV+. Bivariate analysis will be used to examine relations among variables of interest. For constructs assessed using multiple items, factor analysis will be used to confirm the scales, and summary scale scores will be created. Psychometric analysis of the developed measures will be performed; exploratory analyses will be used immediately after alteration or creation to explore redundancy or inadequacy of items; and confirmatory analysis will be used at later waves to examine validity, reliability, and stability of the composite scores.

In addition, Latent Class Analysis provides a parsimonious way to identify specific behaviors characterized by particular patterns of responses and to link subgroup membership to predictors and outcomes. We will use Latent Class Analysis to examine the following: (1) patterns of co-occurring substance use, HIV, STI, and mental health comorbidities; characteristics of engagement in care; and how pattern membership changes over time; (2) patterns of multiple intersecting identities and changes over time; (3) patterns of multidimensional interconnected experiences of stigma and changes over time; (4) how associations among HIV and STIs, substance use, mental health, and engagement in care are informed by intersectionality; and (5) differences between African American and Black and Latino YMSM and TGMY in complex intersectionality processes.

All data and biological samples collected for this study will remain confidential; all participants’ personal information will be coded using a combination of numbers and letters such that the data collected cannot be linked back to the study participants. All personal identifiable information will be removed from self-reported assessments and biological specimens, and any findings in future scientific journals or conferences will be reported in aggregate form and only after the data have been deidentified. All participant data will be deidentified from participant information. All self-reported and collected data will remain in a password-protected database, and all biological specimens will be entered into a secure, password-protected database and be accessible only to the study staff.

This paper describes the renewal of a longitudinal study with efforts to combine 2 different cohorts of YMSM and TGMY into a unified cohort, with distinct study measures adapted for each. We discuss the renewal period and the adoption of new measures to assess psychosocial characteristics that align with our current study aim—adopting a framework of intersectionality to develop effective interventions for YMSM and TGMY, who may experience multiple forms of stigma owing to their multiple minority identities.

As we broach the fifth decade of the AIDS epidemic in the United States, health researchers and AIDS activists reflect on both the progress that has been made in reducing the incidence of AIDS and the importance of continued prevention efforts. Although significant advances have been made in reducing the incidence of new infections, recent studies have demonstrated that some groups continue to have elevated exposure to HIV transmission risk. YMSM and TGMY are such groups, and more traditional risk reduction efforts do not appear to be effectively reaching this population. One of the reasons why more traditional HIV prevention efforts have failed among these young people is that such efforts often fail to incorporate broad familial, social, cultural, and community factors that influence their lives. Very few proven interventions are available that have been targeted for these groups. The importance of this study rests on its potential to generate appropriate and meaningful HIV prevention efforts targeting YMSM of color and TGMY and to integrate current understanding of a range of psychosocial factors and their influence on HIV risk and protective behaviors, particularly drug use and sexual practices.

We will work to ensure that our cohort serves as a national resource for collaborations and dissemination (aim 3). Our cohorts provide unique opportunities for researchers and interventionists to assess and test how we can reach our national goals with 2 key populations: African American and Black and Latino YMSM and TGMY. In particular, the proposed mixed methods study may offer important insights into the broad array of interpersonal, social, and cultural relationships in young people’s lives that underlie their involvement in drug use and HIV risk and protective behavior. This study will provide important information that can be used to develop gender-specific and age-appropriate substance use and HIV prevention and harm reduction efforts.