INTEGRA: A Vanguard Study of Health Service Delivery in a Mobile Health Delivery Unit (INTEGRA)

INTEGRA: A Vanguard Study of Health Service Delivery in a Mobile Health Delivery Unit to Link Persons Who Inject Drugs to Integrated Care and Prevention for Addiction, HIV, HCV and Primary Care

National Institute of Allergy and Infectious Diseases (NIAID), National Institute on Drug Abuse (NIDA)

The purpose of this study is to determine the efficacy of using a mobile health delivery unit ("mobile unit") to deliver "one stop" integrated health services - particularly medication for opioid use disorder (MOUD) and medication for HIV treatment and prevention - to people who inject drugs (PWID) with opioid use disorder (OUD) to improve uptake and use of MOUD, and uptake and use of antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP).

The purpose of this study is to determine the efficacy of using a mobile health delivery unit ("mobile unit") to deliver "one stop" integrated health services - particularly medication for opioid use disorder (MOUD) and medication for HIV treatment and prevention - to people who inject drugs (PWID) with opioid use disorder (OUD) to improve uptake and use of MOUD, and uptake and use of antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP). The intervention arm receiving health services in the mobile unit will be supported by peer navigation. An active control arm will receive peer navigation to health services available at community-based agencies. Impact (cost-effectiveness, mathematical modeling) and implementation factors (mixed methods to identify barriers and facilitators of the interventions) will contextualize findings from the efficacy analysis. The impact of the COVID-19 epidemic in the study population will also be assessed.

Randomized, 1:1 study of 450 participants. Participants in the intervention arm will be provided integrated health services delivered in the mobile unit and peer navigation for 26 weeks. Participants in the active control arm will be provided 26 weeks of peer navigation to connect them to health services available at community-based agencies.

Participants in the intervention arm will be provided integrated health services delivered in the mobile unit and peer navigation for 26 weeks.

Participants in the active control arm will be provided 26 weeks of peer navigation to connect them to health services available at community-based agencies.

Testing and referral for vaccination or treatment for hepatitis A virus (HAV) and hepatitis B virus (HBV)

Evaluate whether the intervention improves use of MOUD, as measured at 26 weeks, by assessing the following endpoint: • Documented current use of MOUD. At the Week 26 visit: Alive Retained Biological evidence of MOUD (any detectable medications) A MOUD prescription current at the Week 26 visit or proof of current receipt of MOUD from a clinic that does not provide individual MOUD prescriptions (e.g., methadone clinics)

Evaluate whether the intervention increases use of PrEP among people without HIV, as measured at 26 weeks, by assessing the following endpoint: • Among participants who were without HIV at enrollment: alive, retained, without HIV, with detectable PrEP drugs in dried blood spot (DBS) samples at the Week 26 visit

Evaluate whether the intervention improves use of MOUD, compared to the active control condition, by assessing the following endpoints: Documented current use of MOUD: alive, retained, with biological evidence of MOUD (any detectable medications) at the week 52 visit and a MOUD prescription current at 52 weeks after enrollment or proof of current receipt of MOUD from a clinic that does not provide individual MOUD prescriptions (e.g., methadone clinics) at the week 52 visit Documented use of MOUD during the study: a MOUD prescription documented during the 52 weeks of study follow-up or proof of current receipt of MOUD from a clinic that does not provide individual MOUD prescriptions (e.g., methadone clinics) during the 52 weeks of study follow-up

Evaluate whether the intervention increases rates of viral suppression among people living with HIV, compared to the active control condition, by assessing the following endpoint: • Among participants living with HIV at enrollment: alive, retained, and virally suppressed (VL <200 copies/mL) at the week 52 visit

Evaluate whether the intervention increases use of PrEP among participants without HIV at enrollment, compared to the active control condition, by assessing the following endpoint(s): Among participants without HIV at enrollment: alive, retained, HIV negative, with detectable PrEP drugs in DBS at the week 52 visit Among participants without HIV at enrollment: alive, retained, HIV negative, with protective levels of PrEP drugs in DBS samples at the week 26 and 52 visits

Evaluate whether the intervention reduces opioid and polysubstance use at 26 and 52 weeks, compared to the active control condition, by assessing the following endpoint: • Alive, retained, and no opioids (natural or synthetic), stimulants (methamphetamine, cocaine) or benzodiazepines detected in urine samples at the week 26 and 52 visits

Evaluate whether the intervention reduces prevalence of bacterial STIs, compared to the active control condition, by assessing the following endpoint: • Alive, retained and no evidence of gonorrhea, chlamydia, or new or recurrent syphilis infection detected at the week 26 and 52 visits

Evaluate whether the intervention reduces the rate of fatal overdose events by 26 and 52 weeks, compared to the active control condition, by assessing the following endpoint: • Death, with overdose as cause

Evaluate whether the intervention reduces the rate of non-fatal overdose events by 26 and 52 weeks, compared to the active control condition, by assessing the following endpoint: • Self-report of non-fatal overdose, collected at week 26 and 52 visits

Assess whether the intervention increases the proportion of participants with undetectable HCV RNA among those with chronic HCV infection at enrollment

Assess whether the intervention increases the proportion of participants with undetectable HCV RNA among those with chronic HCV infection at enrollment, compared to the active control condition, the following endpoint(s) will be assessed: • Undetectable HCV RNA at the week 26 and 52 visits among participants with chronic HCV at enrollment

Evaluate whether the intervention reduces HCV incidence, compared to the active control condition, the following endpoint(s) will be assessed: • HCV antibody positive at the week 52 visit among participants who are HCV antibody negative at enrollment

Evaluate whether the intervention increases rates of viral suppression among participants living with HIV at enrollment

Evaluate whether the intervention increases rates of viral suppression among participants living with HIV at enrollment, as measured at 26 weeks, by assessing the following endpoint: • Among participants living with HIV at enrollment: alive, retained, and virally suppressed (VL<200 copies/mL) at the week 26 visit

Evaluate whether 26 weeks of "one stop" integrated health services delivered in a mobile health delivery unit, supported by peer navigation, increases MOUD use

Evaluate whether 26 weeks of "one stop" integrated health services delivered in a mobile health delivery unit, supported by peer navigation, increases MOUD use, by assessing the following endpoint: • In the intervention arm, change over time in the use of MOUD during the study, comparing documented use of MOUD (biological evidence of MOUD - any detectable medications - and a current MOUD prescription) or proof of current receipt of MOUD from a clinic that does not provide individual MOUD prescriptions (e.g., methadone clinics)) at 26 and 52 weeks to documented use of MOUD at enrollment. MOUD use is assumed to be zero at enrollment due to study exclusion criteria. Follow-up endpoints will be defined as alive, retained, and having documented MOUD use.

Evaluate whether 26 weeks of "one stop" integrated health services delivered in a mobile health delivery unit, supported by peer navigation, increases viral suppression at 26 and 52 weeks

Evaluate whether 26 weeks of "one stop" integrated health services delivered in a mobile health delivery unit, supported by peer navigation, increases viral suppression at 26 and 52 weeks compared to enrollment, by assessing the following endpoint: • Among participants living with HIV at enrollment: change over time in the proportion of people with viral suppression (VL<200 copies/mL), comparing 26 and 52 weeks to enrollment. Follow-up endpoints will be defined as alive, retained, and virally suppressed.

Evaluate whether 26 weeks of "one stop" integrated health services delivered in a mobile health delivery unit, supported by peer navigation, increases PrEP use at 26 and 52 weeks

Evaluate whether 26 weeks of "one stop" integrated health services delivered in a mobile health delivery unit, supported by peer navigation, increases PrEP use at 26 and 52 weeks compared to enrollment, by assessing the following endpoint: • Among participants who were without HIV at enrollment: change over time in the proportion of people with detectable PrEP drugs in DBS at 26 and 52 weeks compared to enrollment. Follow-up endpoints will be defined as alive, retained, and having detectable PrEP.

Evaluate whether 26 weeks of peer navigation to similar health services available at community-based agencies increases MOUD use at 26 and 52 weeks

Evaluate whether 26 weeks of peer navigation to similar health services available at community-based agencies increases MOUD use at 26 and 52 weeks compared to enrollment, by assessing the following endpoint: • In the active control arm, change over time in the use of MOUD during the study, comparing documented use of MOUD (biological evidence of MOUD - any detectable medications - and a current MOUD prescription) or proof of current receipt of MOUD from a clinic that does not provide individual MOUD prescriptions (e.g., methadone clinics)) at 26 and 52 weeks to documented MOUD use at enrollment. MOUD use is assumed to be zero at enrollment due to study exclusion criteria. Follow-up endpoints will be defined as alive, retained, and having documented MOUD use.

Evaluate whether 26 weeks of peer navigation to similar health services available at community-based agencies increases viral suppression at 26 and 52 weeks

Evaluate whether 26 weeks of peer navigation to similar health services available at community-based agencies increases viral suppression at 26 and 52 weeks compared to enrollment, by assessing the following endpoint: • Among participants living with HIV at enrollment: change over time in the proportion of people with viral suppression (VL<200 copies/mL), comparing 26 and 52 weeks to enrollment. Follow-up endpoints will be defined as alive, retained, and virally suppressed.

Evaluate whether 26 weeks of peer navigation to similar health services available at community-based agencies increases PrEP use at 26 and 52 weeks

Evaluate whether 26 weeks of peer navigation to similar health services available at community-based agencies increases PrEP use at 26 and 52 weeks compared to enrollment, by assessing the following endpoint: • Among participants who were without HIV at enrollment: change over time in the proportion of people with detectable PrEP drugs in DBS at 26 and 52 weeks compared to enrollment. Follow-up endpoints will be defined as alive, retained, and having detectable PrEP.

Assess the prevalence of SARS-CoV-2 seropositivity at baseline, 26 and 52 weeks, the following endpoint will be assessed: • Laboratory evidence of antibodies to SARS-CoV-2

Document the impact of the COVID-19 epidemic on participants' experiences of seeking, obtaining and/or maintaining health services, housing, food security and drugs

Document the impact of the COVID-19 epidemic on participants' experiences of seeking, obtaining and/or maintaining health services, housing, food security and drugs, the team will: • Document self-reported subjective experiences linked to COVID-19 when seeking MOUD, HIV care (ART, PrEP), STI testing and treatment, hepatitis screening and treatment, primary care, and harm reduction counseling.

Inclusion Criteria: At least 18 years of age Urine test positive for recent opioid use and with evidence of recent injection drug use ("track marks") Diagnosed with OUD per Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 Able and willing to give informed consent Willing to start MOUD treatment Able to successfully complete an Assessment of Understanding Self-reported sharing injection equipment and/or condomless sex in the last three months with partners of HIV-positive or unknown status Able to provide adequate locator information Confirmed HIV status, as defined in the HPTN 094 Study Specific Procedures Manual Exclusion Criteria: Urine testing that is not negative for methadone within 30 days prior to Enrollment is exclusionary, unless verified hospital records show methadone received as a medication for hospitalization only during the screening period. A volunteer may provide a sample for urine testing more than once during the screening period in order to achieve a negative result. If this criterion cannot be met within 30 days from the start of screening, the individual will be considered a screen failure and the volunteer has up to two more screening chances to successfully complete the screening process again. Received MOUD in the 30 days prior to enrollment by self-report Co-enrollment in any other interventional study unless approved by the Clinical Management Committee (CMC)

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