High Prevalence of Anal High-Grade Squamous Intraepithelial Lesions, and Prevention Through Human Papillomavirus Vaccination, in Young Men Who Have Sex With Men Living With Human Immunodeficiency Virus.

BACKGROUND: Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV)-related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied. METHODS: Two hundred and sixty MSMLWH aged 18-26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24. RESULTS: Among 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type-associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18-associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events. CONCLUSIONS: 18-26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type-associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.

A Uniquely Targeted, Mobile App-Based HIV Prevention Intervention for Young Transgender Women: Adaptation and Usability Study.

BACKGROUND: Young transgender women (YTW) are a key population for HIV-related risk reduction, yet very few interventions have been developed to meet their needs. Mobile health interventions with the potential for both efficacy and wide reach are a promising strategy to reduce HIV risk among YTW. OBJECTIVE: This study aims to adapt an efficacious group-based intervention to a mobile app, Project LifeSkills, to reduce HIV risk among YTW, and to test its acceptability and usability. METHODS: The group-based intervention was adapted to a mobile app, LifeSkills Mobile, with input from an expert advisory group and feedback from YTW collected during user-centered design sessions. A beta version of the app was then tested in a usability evaluation using a think-aloud protocol with debriefing interviews, recordings of screen activity, and assessments of usability via the Post-Study System Usability Questionnaire (PSSUQ) and the Health Information Technology Usability Evaluation Scale (Health-ITUES). RESULTS: YTW (n=8; age: mean 24 years, SD 3 years; racial or ethnic minority: 7/8, 88%) provided feedback on the app prototype in design sessions and then tested a beta version of the app in a usability trial (n=10; age: mean 24 years, SD 3 years; racial or ethnic minority: 8/10, 80%). Both usability ratings (Health-ITUES: mean 4.59, SD 0.86; scale range: 1-5) and ratings for satisfaction and accessibility (PSSUQ: mean 4.64, SD 0.90; scale range 1-5) were in the good to excellent range. No functional bugs were identified, and all mobile activities were deployed as expected. Participant feedback from the usability interviews indicated very good salience of the intervention content among the focal population. Participants' suggestions to further increase app engagement included adding animation, adding audio, and reducing the amount text. CONCLUSIONS: We conclude that the LifeSkills Mobile app is a highly usable and engaging mobile app for HIV prevention among YTW.

Comparing Different Measures of Retention in Care Among a Cohort of Adolescents and Young Adults Living with Behaviorally-Acquired HIV.

Young people living with HIV (YLWH) have some of the lowest rates of retention in HIV care, putting them at risk for negative health outcomes. To better understand retention in care in this age group, we conducted a retrospective cohort analysis of YLWH initiating care at a multidisciplinary, adolescent-focused HIV clinic (N = 344). Retention was calculated using a variety of definitions, and relationships between different definitions were assessed. During the 1-year study period, on average YLWH missed two scheduled appointments, and attended 80% of appointments, usually at least once every 3 months. About one-quarter experienced a 6-month gap in care and about two-thirds met the Health Resources and Services Administration's retention criteria. Although most retention definitions were significantly correlated, not all were. Researchers, clinicians, and policymakers should consider the impact of varying definitions of retention, in order to optimally measure this outcome in YLWH, a key vulnerable population.

The Healthy Young Men's Cohort: Health, Stress, and Risk Profile of Black and Latino Young Men Who Have Sex with Men (YMSM).

Young men who have sex with men (YMSM), especially YMSM of color, are at increased risk for a wide range of threats to their health and well-being. In this study, we recruited and surveyed an urban sample of 448 young African American/Black (Black), Hispanic/Latino (Latino), and multi-racial/ethnic YMSM, ages 16-24 years (mean = 22.3 years), about stressful life events, their health and mental health, their access to and utilization of care, and their involvement in risk-related behaviors. We found that the majority reported experiences of racism (87%) and homophobia (76%). A high percentage reported food insecurity/hunger (36%), residential instability (15%), financial hardship (63%), and conflict with family/friends (62%). The prevalence of risk behaviors was also high, including recent use of tobacco (46%), alcohol (88%), and marijuana (72%), and 41% tested positive for 1+ drugs. Furthermore, 26% tested positive for 1+ sexually transmitted infections (STIs). Over half (56%) reported being worried about their health, 33% reported having a chronic health condition and 31% a mental health condition, and 45% had wanted/needed mental health services during the past year. Further, 17% reported suicidal ideation/had planned a suicide attempt and 26% had ever engaged in self-injurious behaviors. Significant differences by race/ethnicity and HIV status included residential status/food insecurity, type of racism/homophobia, drug use, and STIs. These findings demonstrate how vulnerable this population is with respect to a wide range of structural and social determinants of health that may be important drivers of behavioral, health, mental health outcomes, and potentially long-term health disparities.

HIV-Infected Young Men Demonstrate Appropriate Risk Perceptions and Beliefs about Safer Sexual Behaviors after Human Papillomavirus Vaccination.

The aim of this study was to identify risk perceptions after human papillomavirus (HPV) vaccination among HIV-infected young men who have sex with men. On average, participants appropriately perceived themselves to be at lower than neutral risk for HPV (mean subscale score 4.2/10), at higher than neutral risk for other sexually transmitted infections (7.0/10), and that safer sexual behaviors were still important (8.5/10). Higher perceived risk of HPV was associated with African-American race (p = .03); higher perceived risk of other sexually transmitted infections with White race (p = .01) and higher knowledge about HPV (p = .001); and higher perceived need for safer sexual behaviors with consistent condom use (p = .02). The study provides reassuring data that HIV-infected young men who have sex with men generally have appropriate risk perceptions and believe that safer sexual behaviors after vaccination are still important. These findings mirror the results of studies in HIV-infected young women and HIV-uninfected adolescents.

The Impact of Cell Phone Support on Psychosocial Outcomes for Youth Living with HIV Nonadherent to Antiretroviral Therapy.

Mobile health interventions to promote adherence to antiretroviral therapy among adolescents and young adults living with HIV represent a promising strategy. This pilot study (N = 37) evaluated the psychosocial impacts of an efficacious adherence intervention, cell phone support (CPS). Participants receiving CPS reported significant decreases in perceived stress, depression, and illicit substance use, and increases in self-efficacy during at least one study assessment period, in comparison to participants receiving usual care. Future research using a larger sample should test for mediators of treatment efficacy to further characterize how cell phone interventions impact adherence.

Cell phone support to improve medication adherence among solid organ transplant recipients.

For many adolescent and young adult solid organ transplant recipients, medication non-adherence is a mortal issue. This study investigated the feasibility, acceptability, and potential efficacy of a 12-week cell phone support intervention to improve immunosuppressant medication adherence. A small sample (N = 8) of non-adherent adolescent and young adult transplant recipients, aged 15-20.5 years, was enrolled. Cell phone support consisted of short calls each weekday including medication reminders, discussion of needs, problem-solving support, and promotion of clinic and community resources. Changes in adherence were measured by self-report and laboratory values, and intervention acceptability, adherence barriers, social support, depression, and substance use were assessed by self-report. Pre-post effect sizes showed medium-to-large improvements in adherence, lasting through a 12-week follow-up assessment. There were also small-to-medium changes in adherence barriers, social support, and depression. However, acceptability and feasibility were limited, due to a low rate of enrollment by eligible male participants. Cell phone support interventions may promote medication adherence among adolescents and young adults. Cell phone support warrants further investigation, including a randomized controlled trial to evaluate efficacy.

Preferences for Injectable PrEP Among Young U.S. Cisgender Men and Transgender Women and Men Who Have Sex with Men.

Young men who have sex with men account for approximately 20% of incident HIV infections in the U.S. Antiretroviral pre-exposure prophylaxis (PrEP) administered as a daily pill has been shown to decrease HIV acquisition in at-risk individuals. New modalities for PrEP are being developed and tested, including injectable PrEP; however, acceptability of these emerging modalities has not yet been examined in youth. We conducted six focus groups with 36 young men and transgender men and women who have sex with men in Boston, Chicago, and Los Angeles in 2016 to assess interest in and preference for different PrEP modalities. Youth were purposively recruited based on diversity of age, race/ethnicity, and prior PrEP experience. Data were coded using content coding based on key domains of the interview guide, in particular around the central themes of interest in and barriers and facilitators to injectable PrEP use. Participants were knowledgeable about oral PrEP but suggested barriers to broader uptake, including stigma, marginalization, and access to information. While participants were split on preference for injectable versus oral PrEP, they agreed quarterly injections may be more manageable and better for those who have adherence difficulties and for those who engage in sex more frequently. Concerns specific to injectable PrEP included: severity/duration of side effects, pain, level of protection prior to next injection, distrust of medical system and injections, and cost. Understanding barriers to and preferences for diverse prevention modalities will allow for more HIV prevention options, improved products, and better interventions, thus allowing individuals to make informed HIV prevention choices.

The use of cell phone support for non-adherent HIV-infected youth and young adults: an initial randomized and controlled intervention trial.

This randomized behavioral trial examined whether youth living with HIV (YLH) receiving cell-phone support with study funded phone plans, demonstrated improved adherence and viral control during the 24 week intervention and 24 weeks post-intervention compared to controls. Monday through Friday phone calls confirmed medications were taken, provided problem-solving support, and referred to services to address adherence barriers. Of 37 participants (ages 15-24), 62 % were male and 70 % were African American. Self-reported adherence was significantly higher in the intervention group compared to the control at 24 and 48 weeks for the past month (P = 0.007) and log 10 HIV VL was significantly lower at both 24 weeks (2.82 versus 4.52 P = 0.002) and 48 weeks (3.23 versus 4.23 P = 0.043). Adherence and viral load showed medium to large effect sizes across the 48 week study. This is the first study to demonstrate sustained clinically significant reductions in HIV VL using youth friendly technology.

The initial feasibility of a computer-based motivational intervention for adherence for youth newly recommended to start antiretroviral treatment.

Young people represent the largest number of new HIV infections, thus youth living with HIV (YLH) are likely to be the largest group to initiate antiretroviral treatment (ART). Adherence patterns for behaviorally infected YLH are not adequate to effectively manage the disease; therefore, novel interventions are needed to improve medication adherence. The purpose of the current study, which will precede a randomized controlled trial, was to assess the initial feasibility of an individually tailored computer-based two-session interactive motivational interviewing (MI) intervention for YLH newly recommended to start ART. Intervention development occurred in collaboration with three youth advisory groups. Ten youth (ages 18-24) were recruited to participate in this study. Participants completed the intervention online. Intervention components focused on medication adherence (rating perceived importance and confidence, and goal setting). Retention was 100% for both intervention sessions. All participants (n=10) felt medication adherence was important, but 80% felt confident they could manage their adherence to HIV medications. Ninety percent of participants set the goal of taking their HIV medications exactly as prescribed and reported success achieving this goal at follow-up. Additionally, participants were satisfied with the quality of the sessions and the amount of assistance they received for managing their adherence to HIV medications (90% participants for Session 1; 89% for Session 2). Per exit interview responses, participants felt that the intervention made them think more about their health and was a motivator for them to take better care of their health. In conclusion, the intervention was feasible for YLH enrolled in the study.

Acute HIV Diagnosis After Initiation of Pre-exposure Prophylaxis in a Young Adult Patient: A Case Report.

Oral pre-exposure prophylaxis (PrEP) in the prevention of human immunodeficiency virus (HIV) infection is highly effective, yet the majority of sexually active adolescents and young adults (AYAs) at highest risk for HIV infection, particularly AYA males who have sex with males, have not been prescribed this medication. Provider hesitancy in prescribing PrEP to at-risk AYA patients is often associated with concerns about patient nonadherence and its effect on inducing HIV medication resistance. This case report has two aims. First, to outline the clinical course for an AYA patient prescribed PrEP for 3 months and then found to have HIV with an M184V resistance mutation and subsequently started on HIV treatment. And second, to illustrate how the benefits of PrEP initiation outweigh its risks by presenting clinical data on resistance patterns to PrEP medications. The patient eventually achieved viral suppression within 5 months of starting HIV treatment which has been sustained up to 2 years. This case illustrates that M184V resistance mutations, although rarely associated with PrEP, are unlikely to impact options for HIV treatment. Providers should recommend and prescribe oral PrEP to AYA patients at risk for HIV infection without concern for nonadherence leading to HIV medication resistance.

Youth perspectives on mobile health adherence interventions: A qualitative study guided by the supportive accountability model.

OBJECTIVE: We applied a Supportive Accountability Model lens to understand how youth view remote human coaching versus automated reminders targeting medication adherence. METHODS: We used thematic analysis to interpret (N = 22) youths' responses to semi-structured interviews after 12 weeks of mobile health intervention. RESULTS: Participants reported that both coaching and automated reminders prompted them to take medication, improving their adherence. Participants found coaching helpful because they developed routines and strategies, were motivated to avoid disappointing their coach, and felt their coach cared for them. Automated support could be motivational for some but demanded less engagement. Participants described phone calls as disruptive to their daily lives, but conducive to developing a personal connection with their coach, whereas texts were easier and more flexible. Youth emphasized that individual preferences often differ. CONCLUSION: Human coaching was viewed as a more potent, engaging adherence intervention than automated reminders, although individual needs and preferences differed. Phone calls may enhance the experience of supportive accountability for adherence, but also pose greater acceptability and usability barriers than texting. PRACTICE IMPLICATIONS: Intervention developers should provide opportunities for youth to make personal connections with human adherence supporters and attend to youth preferences for communication modality.

Barriers to medication adherence in behaviorally and perinatally infected youth living with HIV.

The study explored barriers to antiretroviral medication adherence in perinatally and behaviorally HIV infected adolescents and young adults in a cross-sectional, multisite sample. The study included a subset of a convenience sample from a cross-sectional analysis. Participants were youth with HIV ages 12-24 who were prescribed HIV medication and reported missing medication in the past 7 days (n = 484, 28.4 % of protocol sample). The top barriers were similar for perinatally and behaviorally infected youth, but perinatally infected youth reported significantly more barriers. Forgetting, not feeling like taking medication and not wanting to be reminded of HIV infection were the most common barriers reported. Number of barriers was significantly correlated with percent of doses missed, viral load, and psychological distress for perinatally infected youth and with doses missed, psychological distress, and substance use for behaviorally infected youth. Interventions to improve adherence to HIV medications should not only address forgetfulness and choosing not to take medications, but also consider route of infection.

Motivational Enhancement System for Adherence (MESA): pilot randomized trial of a brief computer-delivered prevention intervention for youth initiating antiretroviral treatment.

OBJECTIVE: To pilot test a two-session computer-delivered motivational intervention to facilitate adherence among youth with HIV newly prescribed antiretroviral treatment (ART). METHODS: Youth (N = 76) newly prescribed ART were recruited from 8 sites, and were randomized to the intervention or an active nutrition and physical activity control. Primary outcomes were HIV-1 viral load at baseline, 3 months, and 6 months, and self-reported adherence at 3 and 6 months. RESULTS: Satisfaction ratings were high. Effect sizes suggested that the intervention group showed a greater drop than controls in viral load from baseline to 6 months (Cohen's d = 0.39 at 3 months; d = 0.19 at 6 months), and had greater percent undetectable by 6 months (d = 0.28). Effects sizes were medium to large for 7-day and weekend adherence. CONCLUSIONS: A brief computer-delivered motivational intervention showed promise for youth starting ART and is ready to be tested in a full-scale clinical trial.

Designing an mHealth Roadmap for the Journey to Self-Management: A Qualitative Study with Adolescents and Young Adults Living with Chronic Illness.

OBJECTIVES: Adolescents and young adults (AYA) with chronic illnesses often struggle with illness self-management. The objective of this study is to understand how AYA with various chronic illnesses develop self-management skills and which mobile health (mHealth) strategies they believe could be helpful. METHODS: Semi-structured interviews were conducted with patients, between 16 to 20 years old, living with at least one chronic illness (N = 19), between 2018 and 2019 in Los Angeles, CA. Three coders completed thematic coding to understand how AYA develop and maintain self-management skills, to inform the development of mHealth interventions appropriate across a variety of chronic conditions. RESULTS: Results suggest that AYA develop self-management skills through several strategies, including (1) getting organized, (2) making it work for me and (3) keeping the right mentality. AYA described developing these strategies through: (1) receiving social support, (2) accessing helpful tools and technologies, and (3) going through a maturation process. They provided recommendations for mHealth intervention developers. DISCUSSION: The results suggest that an appealing mHealth intervention could support AYA patients in proactively acquiring self-management skills and prevent having to rely on trial and error or uneven access to guidance and support. Interventions should be responsive to individual technology preferences and practices.

Examining Recruitment Strategies in the Enrollment Cascade of Youth Living With HIV: Descriptive Findings From a Nationwide Web-Based Adherence Protocol.

BACKGROUND: Digital strategies and broadened eligibility criteria may optimize the enrollment of youth living with HIV in mobile health adaptive interventions. Prior research suggests that digital recruitment strategies are more efficient than traditional methods for overcoming enrollment challenges of youth living with HIV in the United States. OBJECTIVE: This study highlights the challenges and strategies that explain screening and enrollment milestones in a national web-based adherence protocol for youth living with HIV. METHODS: Baseline data from a national web-based HIV adherence protocol for youth living with HIV, collected from July 2018 to February 2021, were analyzed. A centralized recruitment procedure was developed, which used web-based recruitment via Online Master Screener; paid targeted advertisements on social media platforms (eg, Facebook and Reddit) and geosocial networking dating apps (eg, Grindr and Jack'd); and site and provider referrals from Subject Recruitment Venues and other AIDS service organizations, website referrals, and text-in recruitment. RESULTS: A total of 3 distinct cohorts of youth living with HIV were identified, marked by changes in recruitment strategies. Overall, 3270 individuals consented to screening, 2721 completed screening, 581 were eligible, and 83 completed enrollment. We examined sociodemographic and behavioral differences in completing milestones from eligibility to full enrollment (ie, submitting antiretroviral therapy and viral load data and completing the baseline web-based survey). Those with the most recent viral load tests >6 months ago were half as likely to enroll (odds ratio 0.45, 95% CI 0.21-0.94). Moreover, eligible participants with self-reported antiretroviral therapy adherence (SRA) between 50% and 80% were statistically significant (P<.001 to P=.03) and more likely to enroll than those with SRA >80%. CONCLUSIONS: The findings add to our knowledge on the use of digital technologies for youth living with HIV before and during the COVID-19 pandemic and provide insight into the impact of expanding eligibility criteria on enrollment. As the COVID-19 pandemic continues and the use of and engagement with social media and dating apps among youth living with HIV changes, these platforms should continue to be investigated as potential recruitment tools. Using a wide variety of recruitment strategies such as using social media and dating apps as well as provider referral mechanisms, increasing compensation amounts, and including SRA in enrollment criteria should continue to be studied with respect to their ability to successfully recruit and enroll eligible participants. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/11183.

Pediatric subspecialty healthcare providers' views of recruitment during a randomized controlled trial of a mobile health intervention.

Background: Randomized clinical trials (RCTs) enrolling pediatric populations often struggle with recruitment. Engaging healthcare providers in the recruitment process may increase patients' and caregivers' willingness to participate in research. The purpose of this study was to understand the perspectives of pediatric subspecialty healthcare providers considering recruiting patients to participate in an mobile health (mHealth) RCT. Methods: We conducted 9 semi-structured interviews and 1 focus group with a total of N = 11 providers from various disciplines before the initiation of an mHealth RCT addressing medication nonadherence. Then, we conducted 5 follow-up interviews and 1 follow-up focus group with a total of 8 of these providers several months later. We used thematic analysis to generate themes describing providers' views of the RCT and patient recruitment. Results: Providers indicated that they were willing to recruit for this study because they believed that the intervention sought to address a significant problem. They also thought it made sense to intervene using technology for this age group. However, many providers thought that certain patients (e.g., those with mild, shorter-lasting adherence difficulties) were the most appropriate to recruit. They described how keeping the trial front of mind facilitated recruitment, and they advised researchers to use strategies to promote their ongoing awareness of the study if conducting similar research in the future. Conclusion: Pediatric healthcare providers are important stakeholders in mHealth intervention research. Engaging them in participant recruitment is a complex endeavor that might promote patient enrollment, but their views of research and demanding clinical roles are important to understand when designing study procedures.

Syndemic theory and HIV-related risk among young transgender women: the role of multiple, co-occurring health problems and social marginalization.

OBJECTIVES: We assessed whether multiple psychosocial factors are additive in their relationship to sexual risk behavior and self-reported HIV status (i.e., can be characterized as a syndemic) among young transgender women and the relationship of indicators of social marginalization to psychosocial factors. METHODS: Participants (n = 151) were aged 15 to 24 years and lived in Chicago or Los Angeles. We collected data on psychosocial factors (low self-esteem, polysubstance use, victimization related to transgender identity, and intimate partner violence) and social marginalization indicators (history of commercial sex work, homelessness, and incarceration) through an interviewer-administered survey. RESULTS: Syndemic factors were positively and additively related to sexual risk behavior and self-reported HIV infection. In addition, our syndemic index was significantly related to 2 indicators of social marginalization: a history of sex work and previous incarceration. CONCLUSIONS: These findings provide evidence for a syndemic of co-occurring psychosocial and health problems in young transgender women, taking place in a context of social marginalization.

Identification of ongoing human immunodeficiency virus type 1 (HIV-1) replication in residual viremia during recombinant HIV-1 poxvirus immunizations in patients with clinically undetectable viral loads on durable suppressive highly active antiretroviral therapy.

In most human immunodeficiency virus type 1 (HIV-1)-infected individuals who achieve viral loads of <50 copies/ml during highly active antiretroviral therapy (HAART), low levels of plasma virus remain detectable for years by ultrasensitive methods. The relative contributions of ongoing virus replication and virus production from HIV-1 reservoirs to persistent low-level viremia during HAART remain controversial. HIV-1 vaccination of HAART-treated individuals provides a model for examining low-level viremia, as immunizations may facilitate virus replication and sequence evolution. In a phase 1 trial of modified vaccinia virus Ankara/fowlpox virus-based HIV-1 vaccines in 20 HIV-infected young adults receiving HAART, we assessed the prevalence of low-level viremia and sequence evolution, using ultrasensitive viral load (<6.5 copies/ml) and genotyping (five-copy sensitivity) assays. Viral evolution, consisting of new drug resistance mutations and novel amino acid changes within a relevant HLA-restricted allele (e.g., methionine, isoleucine, glutamine, or arginine for leucine at position 205 of RT), was found in 1 and 3 of 20 subjects, respectively. Sequence evolution was significantly correlated with levels of viremia of between 6.5 and <50 copies/ml (P = 0.03) and was more likely to occur within epitopes presented by relevant HLA alleles (P < 0.001). These findings suggest that ongoing virus replication contributes to low-level viremia in patients on HAART and that this ongoing replication is subject to CD8(+) T-cell selective pressures.

Sexual risk taking among transgender male-to-female youths with different partner types.

OBJECTIVES: We examined associations between partner types (categorized as main, casual, or commercial) and sexual risk behaviors of sexually active male-to-female (transgender female) youths. METHODS: We interviewed 120 transgender female youths aged 15 to 24 years recruited from clinics, community-based agencies, club and bar venues, referrals, and the streets of Los Angeles, California, and Chicago, Illinois. RESULTS: Sexual risk behaviors varied by partner type. Transgender female youths were less likely to use condoms during receptive anal intercourse with their main partner and were less likely to use condoms with a main partner while under the influence of substances. Youth participants were also more likely to talk to a main partner about their HIV status. Our data identified no demographic or social factors that predicted condom use during receptive anal intercourse by partner type. CONCLUSIONS: Research and interventions that focus on understanding and mitigating risk behaviors by partner type, especially those that tackle the unique risks incurred with main partners, may make important contributions to risk reduction among transgender female youths.