A number of systemic barriers and risk behaviors drive high HIV infection rates among youth experiencing homelessness. Youth experiencing homelessness have earlier sexual debuts; are more likely to have multiple sexual partners; and trade sex for food, shelter, money, drugs, or alcohol [1,2]. They are more likely to use substances before sex, are less likely to use condoms, and are overrepresented by youth who identify as men who have sex with men; each of these characteristics increase risk for HIV [3,4], and those who trade sex are at high risk for HIV infection as they are rarely able to negotiate condom use due to the power dynamics [5] and often lack knowledge about biomedical advances in HIV prevention such as preexposure prophylaxis and nonoccupational postexposure prophylaxis [6]. In a recent 7-city (Houston, Denver, St. Louis, Phoenix, Los Angeles, San Jose, New York City) study of 1427 youth experiencing homelessness (58% male, 81% youth of color, 31% lesbian, gay, bisexual, transgender, queer [LGBTQ]), 71% of participants had little to no knowledge of preexposure prophylaxis [7]. Reassuringly, 53% of study participants had undergone HIV testing in the preceding 3 months [7]. Unfortunately, youth experiencing homelessness experience sexual assault and forced sex at high rates (22% and 24% respectively); yet only 29% received a postsexual assault examination which is when they could have received nonoccupational postexposure prophylaxis and sexually transmitted infection (STI) treatment [8]. The Society for Adolescent Health and Medicine has recommended the development of screening tools, skill-building interventions, and accessible preexposure prophylaxis delivery models for all youth and young adults, particularly those experiencing disparities [9].

HIV risk among youth experiencing homelessness is further exacerbated by multiple comorbid conditions, including mental illness and substance use. Suicide is one of the leading causes of death among youth experiencing homelessness [10], with suicide attempt rates ranging from 12% to 48% [11-13]. Rates of depression and posttraumatic stress among youth experiencing homelessness vary across studies with ranges from 8% [14] to 61% [15] and 5% to 48% [16-18], respectively. A recent study [19] found that 42% of youth experiencing homelessness reported being moderately to severely stressed, 48% experienced mental distress, 48% had depression, and 23% had posttraumatic stress. Depression among youth experiencing homelessness may be due to a lifetime of adversity, abuse, neglect, and housing instability [20,21]—all of which can lead to inhibition and riskier sexual decision making and behavior [22]. Furthermore, rates of substance use are twice those of housed youth [3,23]. In one study [24], 86% of youth experiencing homelessness (n=173) met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for a substance use disorder compared with only 14.2% in the general young adult population [25]; drug overdose is a leading cause of death among youth experiencing homelessness [10]. HIV prevention efforts should address mental health and the intersection of substance use and sexual behaviors.

Youth experiencing homelessness are underserved by the health care system for several reasons. Structural barriers include transportation, lack of health insurance, and costs [26]. Youth also suggest that fear of or past experiences of being judged, dismissed, or discriminated against by health care professionals reduce utilization [27]. Other barriers to health care access include fear of social service agency notification or legal intervention, lack of familiarity with health care resources, and lack of affordability [28]. As a result, youth experiencing homelessness often interact with the health care system at lower rates than their housed peers and frequently overutilize emergency departments for care while experiencing reduced access to prevention services [3]. Therefore, it is essential to increase access to and availability of HIV prevention services, and these services should be colocated with other service programs to foster trust and increase accessibility for youth experiencing homelessness [29-31]

A recent systematic review [32] of interventions to prevent HIV among youth experiencing homelessness highlighted the paucity of HIV prevention research and concluded that more research is necessary. Interventions for youth experiencing homelessness should include the full continuum of behavioral and biomedical HIV prevention, including HIV and STI screening and treatment, preexposure prophylaxis, and nonoccupational postexposure prophylaxis [33]. Engagement in these prevention services requires interventions to increase preexposure prophylaxis awareness, screen for preexposure prophylaxis eligibility, promote condom use, provide assistance with health care navigation that includes care for mental health and substance use issues [34], and address transportation and health insurance challenges. Individuals impacted by mental illness, homelessness, and substance use have greater preexposure prophylaxis uptake and adherence when these abovementioned issues are also addressed [35]. Nurse case management is an evidence-based strategy that has been effective in addressing the multifaceted and complex health and social challenges of HIV prevention among youth experiencing homelessness [27,36-38]

A nurse-led intervention allows for multiple HIV prevention services to be delivered during a single visit (eg, preexposure prophylaxis, nonoccupational postexposure prophylaxis, lab draws, STI testing and treatment), which may increase adherence. This is particularly important as being homeless can decrease effectiveness of linkages to care [39] as opposed to providing that care at the point of contact. Nurse case management has been efficacious in reducing drug use among methadone users [40] and youth experiencing homelessness [41], improving hepatitis B vaccination rates [42], and facilitating HIV care coordination [43]. This comprehensive approach of simultaneously addressing concomitant problems (eg, mental health, substance use, and housing needs), incorporating the full continuum of behavioral and biomedical HIV prevention, is a promising strategy for engaging youth experiencing homelessness in HIV prevention. Given the widespread integration of nurses into current HIV programs serving youth experiencing homelessness, nurse-led interventions are likely scalable and can be integrated into existing HIV prevention programs.

To further engage youth experiencing homelessness, they should be met “where they are” [35] and interventions should be implemented in collaboration with existing health and social service providers by colocating the study activities at drop-in centers, shelters, and service providers that are highly used by youth experiencing homelessness. This strategy is particularly important given that past-month use of a drop-in center has been shown to predict HIV and STI testing [44], increase service utilization, and improve HIV-related outcomes [31]. These findings support the potential of delivering HIV prevention in drop-in centers and shelters to connect youth experiencing homelessness to other underutilizing services and health care. Moreover, drop-in centers may be a preferred HIV prevention service location of youth experiencing homelessness [31]. By integrating the delivery of HIV risk reduction interventions into already-established social services, we may enhance HIV prevention, increase retention, and improve access to mental health, substance use, and housing services.

Nurse-led interventions can also integrate evidence-based strategies that have proven effective in increasing motivations for behavior change. Increasing motivation is particularly important for populations that are potentially overwhelmed by multifaceted and complex health and social challenges. Motivational interviewing is a person-centered counseling style that aims to strengthen a person’s motivation and commitment to change and addresses ambivalence about behavior change [45]. Motivational interviewing has been successfully used with youth to improve uptake of and adherence to health behaviors resulting in reduced alcohol [46] and substance use [47], and increased condom [48] and contraceptive use [49]. Youth experiencing homelessness are self-reliant, can be challenging to engage, and may be distrustful of adults due to past trauma and victimization on the streets [50,51]. Motivational interviewing strategies can strengthen the relationship between the youth experiencing homelessness and providers to evoke participant driven HIV prevention goals [52].

Behavioral feedback technology might also increase motivation to change behavior as tailored and targeted feedback could further engage youth experiencing homelessness. Smartphone-based daily ecological momentary assessments have been used with youth experiencing homelessness. Instant feedback enhances cognitive appraisal of health-seeking and coping behaviors and increases motivation in youth experiencing homelessness [52,53]. Like many adolescents and young adults, youth experiencing homelessness underestimate their HIV risk [7], suggesting that self-monitoring may assist in aligning their behaviors with their perceived HIV risk. Immediate self-monitored behavioral feedback has been found to increase condom use [52,54]. A high number of youth have phones, and young adults, in general [55-57], and youth experiencing homelessness, specifically, have a preference to use technology [58]. A review [59] of 42 studies showed high ecological momentary assessments completion rates (78%) among youth. Prior studies [60] have found similar high adherence rates (82%-87%) with homeless and vulnerable populations.

This study describes the design and implementation of a nurse case management intervention (Come As You Are) efficacy trial with youth experiencing homelessness aged 16 to 25 years who received the active intervention or usual care. The intervention aims to increase uptake of HIV prevention strategies (eg, pre- and postexposure prophylaxis uptake, HIV testing, STI screening and treatment, sober sex, and condom use) when compared with usual care youth experiencing homelessness immediately postintervention and 3, 6, and 9 months postintervention. The study also aims to determine whether the intervention improves mental health symptoms, substance use, and housing status. Additionally, we will assess whether health seeking, coping, HIV risk perception, pre- and postexposure prophylaxis barriers and facilitators, and condom self-efficacy mediate the effect of the intervention on uptake prophylaxis, condom use, and HIV/STI testing. This protocol paper describes the study design, intervention, recruitment, and retention strategies.

This study uses a 2-armed randomized controlled trial design with a wait-list control group to determine the efficacy of the intervention compared to usual care. The primary outcomes are the uptake of HIV prevention strategies (preexposure prophylaxis and nonoccupational postexposure prophylaxis, HIV and STI testing, and condom use). Secondary outcomes of the intervention include the impact on mental health, substance use, and housing status. Follow-up surveys are conducted immediately after the 3-month intervention period and 3, 6, and 9 months postintervention (Figure 1).

Participants are randomly assigned to the intervention or wait-list control arm using a computer-generated blocked 2:1 allocation. By the end of the recruitment period, we anticipate that 300 participants will be randomized to the intervention arm and 150 randomized to the wait-list control arm. Participants are informed in which group they are allocated after completing the baseline survey.

Utilizing numerous recruitment sites in Houston—drop-in centers, shelters, local youth experiencing homelessness service locations, clinics, federally qualified health care centers in locations with a high concentration of homelessness, magnet (eg, hot meal) events, mobile clinics, and street outreach—will increase generalizability of the findings by including a sample of both connected and disconnected youth experiencing homelessness. These recruitment sites serve young men, women, families, and LGBTQ youth. We make use of group-based study introduction sessions, flyers, and recruitment letters at the agencies, clinics, street outreach, and the website and Facebook pages of the agencies and Homeless Youth Network of Houston. We have used these methods successfully in previous studies [61]. The research staff will maintain a consistent, weekly presence at the recruitment sites throughout the study to facilitate both recruitment and follow-up efforts. In response to COVID-19 physical distancing requirements and shelter closures, we are also using snowballing participant referral techniques and online advertisements.

Our sample is limited to youth, 16 to 25 years old, to align with youth homelessness services providers and adolescent risk behavior studies [7], current guidelines for preexposure prophylaxis and nonoccupational postexposure prophylaxis use [62,63], and evidence that experiencing homelessness as a young adult under 26 years of age is associated with heightened sexual risk behaviors and substance use [33]. Individuals are eligible to be included if they (1) are 16 to 25 years old, (2) speak English, (3) are experiencing homelessness, and (4) are not planning to move out of the Houston metropolitan area during the study.

Experiencing homelessness is defined as having slept on the streets, in a place not meant for habitation, in a shelter, hotel or motel, or with someone where they cannot stay for more than 30 days (eg, couch surfing). Youth experiencing homelessness may stay in emergency shelters or on the streets (eg, parks and tent cities); in abandoned or vacant buildings or apartments; temporarily with friends, family, or acquaintances; or in rented hotel or motel rooms [35], and they can go to great lengths to stay hidden from the dangers of victimization [50]. This broad definition of homelessness aligns with the McKinney-Vento Homeless Assistance Act of 1987 [64], which allows us to account for the transiency and instability of housing experienced by youth experiencing homelessness and increases the generalizability of the study findings.

Youth with very low literacy (Rapid Estimate of Adult Literacy in Medicine-Short Form [65] health literacy assessment score <4)[1] are excluded from the study due to the need to independently read the daily smartphone-based assessments. Additionally, youth who are noticeably intoxicated or experiencing acute mental distress are encouraged to be screened for enrollment at a later time to assure safety and acute needs are met prior to enrollment. Youth are connected to services at the recruitment sites for acute needs.

Due to the transient nature of the study population, study participants are being enrolled in a stepwise process that takes place over the course of 3 weeks. The first step entails a thorough review of the consent form and collection of contact information including a photo, and the second step consists of baseline data collection. During the third step, participants receive the study phone and are notified of study group assignment. Intervention participants receive the first intervention session on the same day that they receive the study phone. During the COVID-19 pandemic, consenting and the baseline survey are being completed remotely as needed to reduce the face-to-face study visits to only 1 enrollment visit.

The Come As You Are intervention is based on the Comprehensive Health Seeking and Coping Framework (CHSCF; Figure 2), which describes how the nurse and client work together to mutually develop goals and strategies to improve health in a context of nonjudgmental acceptance. Accomplishment of goals occur by addressing cognitive appraisals (clarifying misconceptions), promoting health seeking, and addressing knowledge and coping behaviors that incorporate the situational, personal, social, and resource needs affecting health. The intervention involves coordinated, individualized, comprehensive care delivered by a nurse that includes a comprehensive health assessment, mutual care plan development, prevention education, and health and social service navigation [36-38,41]. An individualized, rather than group based, intervention was chosen for this study due to the heterogeneity of youth experiencing homelessness and their risk behaviors and the challenges associated with group session designs, including low attendance [66]. The intervention has 2 main components: 6 face-to-face sessions with a study nurse and a behavioral assessment and feedback app. Additionally, booster calls are made monthly for 3 months following the last face-to-face session. This intervention is guided by the CHSCF [67] and uses motivational interviewing [45,68] strategies to promote behavior change and uptake of HIV prevention strategies by facilitating goal setting and evoking change talk.

Youth in the control condition receive usual care from the recruitment sites including assistance with housing, food and clothing needs; basic health assessments and health care; limited anticipatory guidance; access to mental health counseling; substance use treatment referrals; and preexposure prophylaxis or nonoccupational postexposure prophylaxis referrals. Youth receiving usual care also receive a study phone and complete the baseline, 3-, 6-, and 9-month follow-up surveys. After the 12-month study period is completed, youth in the control group are invited to access the full Come As You Are intervention.

A Community Advisory Group and Youth Working Group provided input on study procedures, protocol implementation and will be active in the interpretation and dissemination of the findings to the community. These groups assisted in the development of study procedures, survey items, and recruitment materials. Additionally, they oversaw the creation of a local homeless resource guide to be given to all participants at the time of enrollment and preprogrammed into the study-issued phones. This guide contains location and contact information for local shelters, meals, social, legal, and education services, and clinics. These resources are available in paper version and preloaded to the phones (ie, suicide hotline, shelter contacts) for all participants. The Community Advisory Group are current service providers for youth experiencing homelessness. The Youth Working Group members are youth with lived homelessness experiences between the ages of 18 to 25 years.

Data collected include baseline and follow-up survey data, HIV and STI test data, and data from smartphone-based daily ecological momentary assessments. Assessments are collected at baseline, at the end of treatment (3 months postbaseline), and 3, 6, and 9 months postintervention using REDCap (Vanderbilt University). The surveys are done in person or through a link to the survey sent to the participant via text message or email. The baseline survey assesses demographics (eg, age when first experiencing homelessness, duration experiencing homelessness, race and ethnicity, sexual orientation, gender identity), psychosocial factors, sexual behaviors, substance use, and mental health. The end of treatment assessment for the intervention group contains intervention process outcome items including what participants found to be the most and the least helpful, what made it easy or difficult to attend sessions. HIV and STI test data are collected at baseline, at the end of treatment, and 3, 6, and 9 months postintervention. Table 2 outlines measures used for primary outcomes. Youth with a positive STI test receives treatment and care coordination from the Healthcare for the Homeless Houston program, shelter clinics, or their medical home when preferred. Youth who test positive for HIV during the study will be linked to HIV care at a local clinic by the nurse.

For HIV testing, we use the INSTI HIV-1/HIV-2 Rapid Antibody Test (99.5% sensitivity, 100% specificity; Biolytical Laboratories Inc)[82]. Urine specimens are collected and transported on the same day to a local clinic to test for Chlamydia trachomatis and gonorrhea (Neisseria gonorrhoeae), and results are shared with participants via phone call or in person. Blood samples are tested for syphilis (Treponema pallidum) using an antibody rapid immunochromatographic test (Syphilis Health Check, Trinity Biotech plc)[83]. Due to restrictions on in-person study visits during the COVID-19 pandemic, additional options for STI testing, including going to conveniently located partner clinics or receiving an at-home STI testing kits, are being provided to study participants as attrition mitigation strategies.