Screen 2 Prevent (S2P): Using Digital Health to Improve HIV Screening and Prevention for Adolescents in the Emergency Department

• Using EMRs in EDs – part of standard of care screen/decision making tool to test for HIV: Goal = Get HIV- onto PrEP; get HIV+ onto ART
• Sample size – tens of thousands?
• 5 sites

*Companion study

Linking Youth to PrEP Services (LYPS): An innovative mobile delivery and mHealth intervention to optimize PrEP adherence and persistence among young gay, bisexual, and other men who have sex with men

• Deliver injectable (post-approval for age 18+; study in < 18) PrEP to homes; supported by MHEALTH App
• On drug 9 mos.
• Sample size – a couple of 100
• Will look at getting drug donated (Pharma co.?)

SLC bringing in lab capacity for PK and adherence measures

Legal, Economic, and Affirming Peer Support (LEAP): A status-neutral multicomponent intervention to improve HIV prevention and care continua outcomes among transgender and gender diverse youth

• TG & non-binary youth – 3 components: Economic (micro-grants/financial literacy); legal advice; empowerment intervention: Goal is reduction in risk and uptake of PrEP or ART, as applicable.

May possibly do substudy with TG women because currently PrEP is not recommended due to interaction with hormones (would include specimens)

MPT Study (under an IND): Developing a novel, multipurpose injectable product containing cabotegravir (CAB) and levonorgestrel (LNG) for healthy, HIV negative youth assigned female at birth (AFAB) in the United States (US), including transgender and gender diverse (TGD) youth

• Cisgender women and TG men
• Sample size ~ 100
• Combo injectable contraception (Levonorgestrel) + injectable ARV
• Intensive PK (JHU Lab)
• Repository
• 2^nd phase if PK predicts that this might be co-formulated

CONRAD would hold IND)

LEN BRIDGE (under an IND): Safety, Tolerability, Acceptability and Pharmacokinetics of Novel, Long-Acting Injectable

Lenacapavir for the Prevention of HIV among Adolescents under age 18

• Lenacapavir (subcue injectable for PrEP)
• Currently in Ph. III for adults. Proposing age < 18.
• All genders
• Sample size ~ 100

3 injections over 18

Impact: Hybrid Type 2 Effectiveness-Implementation Trial of Status Neutral, Integrated Behavioral Activation and Risk Reduction Intervention for Stimulant Use Among Sexually Active Young GBMSM

• Gay/Bi MSM
• Substance use (stimulant use)
• Outcomes are sex. Risk reduction & PrEP or care/engagement/ART

Linking Youth to PrEP Services (LYPS): SLC bringing in lab capacity for PK and adherence measures

Keith Horvath, PhD’s Lab @San Diego State Univ.

PROJECT SUMMARY

Youth ages 13-24 comprised 21% of all new cases in 2019, most of which were among Black and Latinx young gay, bisexual, and other men who have sex with men (YGBMSM). While PrEP is highly effective in preventing new HIV infections, studies of YGBMSM show sub-optimal PrEP care continuum outcomes. Alternative models of service delivery that extend outside of the clinic are needed to reach adolescents and highest-risk young people with PrEP. Numerous barriers to meeting the demands of remaining engaged in clinic-based PrEP care exist for adolescents, including distance to clinics that offer PrEP, times and locations that are not accessible, lack of adolescent friendly services, stigma, and costs associated with accessing care, to name a few. Offering out-of-clinic PrEP delivery options provide substantial opportunities to reach and engage stigmatized communities to improve PrEP continuum of care outcomes. Furthermore, complementing out-of-clinic PrEP care with a flexible mobile Health (mHealth) tool may provide critical support for overcoming real-world challenges. To address these crucial barriers, we propose to assess the efficacy and cost-effectiveness of the LYPS (Linking Youth to PrEP Services) intervention to optimize PrEP adherence and persistence among diverse YGBMSM. LYPS combines novel mobile PrEP and PrEP care services delivery features with a smartphone app that facilitates the tailoring of PrEP agent (e.g., CAB-LA, oral daily) and dosing strategies (e.g., daily, on-demand) to the needs of YGBMSM to address both structural and individual-level barriers to PrEP. In Aim 1, we will refine and finalize LYPS components through iterative input from youth and scientific advisors, followed by usability testing with up to 10 YGBMSM to finalize intervention components and study procedures. In Aim 2, we will determine the efficacy of the LYPS intervention to increase the proportion of YGBMSM who achieve protective levels of PrEP and remain in PrEP care compared to an enhanced standard of care. 272 YGBMSM (13-24 years of age) who are on PrEP (but sub-optimally adherent), starting PrEP, or restarting PrEP will be recruited and randomized (1:1) to receive the LYPS intervention or enhanced standard of care (SOC). YGBMSM will have access to the LYPS intervention for 9 months, with 3-, 6- and 9-month visits to collect survey, clinical, and biological data to assess PrEP adherence and persistence outcomes. Primary outcomes at month 9 are: a) protective levels of PrEP assessed either by dried blood spot samples or medical chart review; and b) the proportion of YGBMSM on PrEP. Finally, Aim 3 will evaluate the resource use costs and costeffectiveness of LYPS to inform interpretation and implementation of study results. The proposed multilevel LYPS intervention is, to our knowledge, the first in the US to combine Mobile Delivery of PrEP services with an mHealth intervention that has the potential to revolutionize PrEP care for both existing PrEP formulations, as well as new options such as CAB-LA. The findings may be replicated across both urban and rural areas of the US to reach the End of the HIV Epidemic goals for YGBMSM.

PrEP Choice

Drs. Buchbinder, Liu and Scott from Bridge HIV, an Francisco Dep’t of Public Health (SFDPH)

Collaborators: UCSF (Dr. Seidman) and 2) CHOP (Dr. Miller).

PROJECT SUMMARY

Young persons, aged 13-24 years, accounted for 21% of new infections in the United States in 2018, and 81% of these occurred in young gay, bisexual, and other men who have sex with men (YGBMSM). Currently, there are 4 different regimens of pre-exposure prophylaxis (PrEP) available for YGBMSM: 1) daily tenofovir disoproxil fumarate co-formulated with emtricitabine (TDF/FTC), 2) daily tenofovir alafenamide co-formulated with emtricitabine (TAF/FTC), 3) peri-coital TDF/FTC (“2-1-1 PrEP”), and 4) injectable long-acting cabotegravir. PrEP Choice is a package of three mobile health tools designed to increase the uptake and adherence to PrEP for YGBMSM, aged 13-24 years, to be tested in multiple sites in the United States. PrEP Choice consists of 1) MyPrEP, a website to help YGBMSM choose the type of PrEP that works best for them; 2) PrEPmate, a twoway SMS texting tool to check in with YGBMSM on a weekly basis and troubleshoot any problems with PrEP that arise; and 3) PrEPsmart, an app that reminds PrEP users taking PrEP pills when their next pill should be taken. These tools have been developed and tested individually; this is the first study to test the package of these tools to see if they increase the proportion of YGBMSM who take PrEP, and their adherence to PrEP once they start. The study begins by ensuring that PrEP Choice is relevant for both Spanish- and Englishspeaking YGBMSM across the country, through the use of focus groups, followed by a technical pilot in 20 YGBMSM, to work out any bugs in the system and to help determine how best to apply PrEP Choice in this population. Then, 200 YGBMSM not currently on PrEP will be recruited into a trial in which 100 are randomly chosen to get PrEP Choice, and the other 100 are randomly chosen to get a brochure describing the different types of PrEP available. After 9 months of follow-up, PrEP starts and use over time will be compared between the two groups. Then, the 100 participants initially given the brochure only will get access to the PrEP Choice package, and both groups will be followed for another 9 months to study their use of PrEP over time. PrEP use will be measured by testing for tenofovir diphosphate (TFV-DP) levels in dried blood spots (for the 3 types of PrEP that use pills) or the number of PrEP injections they get (for injectable long acting cabotegravir.) The primary outcome is PrEP use at 9 months into the study, and this study will enroll enough participants to be able to tell whether there is at least a 20% increase in the proportion of YGBMSM who use any PrEP in the PrEP Choice group compared with the brochure group, and a 22.5% increase in PrEP adherence (as measured by TFV-DP levels or administration of long-acting cabotegravir) in the PrEP Choice group compared with the brochure group. The cost and cost-effectiveness of the PrEP Choice package will also be assessed for YGBMSM. The trial will be conducted through the Adolescent Trials Network for HIV/AIDS Interventions (ATN), making use of their biostatistical and modeling resources, geographic and site diversity, and multidisciplinary expertise, including young advisors from the target population.

Legal, Economic, and Affirming Peer Support (LEAP)

Dr. Gamarel, University of Michigan

PROJECT SUMMARY

In the United States (US), transgender and gender diverse (TGD) youth have high rates of new HIV diagnoses, with Black, Latinx, and other TGD youth of color representing the majority of these cases. The HIV prevention and care continua emphasize the need to reduce HIV transmission risk via regular HIV testing, consistent condom use, and linkages to HIV prevention and care, such as pre-exposure prophylaxis (PrEP) among HIV negative individuals and antiretroviral therapy (ART) and viral suppression among people living with HIV. However, there are inequities at each step of these continua among TGD youth of color. TGD youth of color experience intersectional oppression that results in unmet gender affirmation, legal, and economic needs, which have been linked to inequities in HIV prevention and continua outcomes. Building on formative work, this project seeks to test the effectiveness of the LEAP intervention, a HIV status-neutral intervention designed to address social determinants of health to reduce sexual risk behaviors, increase HIV prevention uptake (PrEP use), and treatment outcomes (viral suppression). LEAP will harness the resources, geographic diversity, and multidisciplinary expertise of the Adolescent Trials Network for HIV/AIDS Interventions (ATN) to provide gender-affirming individualized HIV prevention and treatment peer support, address health-harming legal needs, and improve educational and employment outcomes for translation into real-world practice. We propose a hybrid type 1 effectiveness-implementation study focused on testing the effectiveness of LEAP and secondarily conducting a prospective implementation process evaluation. HIV risk will be assessed using a composite indicator of risk, which is a binary HIV risk indicator of validated measures of sexual risk behavior, as well as self-reported and biomarkers of HIV status, PrEP use, and viral suppression. We will recruit and randomize 250 TGD youth of color from five different ATN Site Consortiums (stratified by site, HIV status, and gender), following participants for 12 months and collecting biological (i.e., HIV status, PrEP use, or viral load) and behavioral data. Findings will provide critical insights into the effectiveness of an urgently needed multicomponent intervention designed to address unmet gender affirmation, legal, and economic needs to reduce HIV inequities among TGD youth of color.

MPT Study (under an IND):

Wits Reproductive Health & HIV Institute (Wits RHI), Johannesburg, South Africa.

Collaborators: JHU, including their Clinical Pharmacology Analytical Laboratory (CPAL) (Director, Marzinke)

PROJECT SUMMARY

Adolescents assigned female at birth (AFAB) in the United States (US) have unmet needs for pregnancy

and HIV prevention; 75% of pregnancies in adolescents are unplanned and 12% of new HIV diagnoses occur in youth aged 13-24 years AFAB. Sexual and gender minority (SGM) youth may have particular vulnerabilities and yet their sexual and reproductive health needs are often overlooked or misunderstood. Multi-purpose prevention technology (MPT) products that can simultaneously prevent pregnancy, suppress menses, and prevent HIV are desirable, may bring efficiencies to both users and healthcare systems, and may serve to improve uptake of HIV prevention products among youth. Early studies suggest that adolescents AFAB would prefer an MPT that is discreet and long-lasting, with injections being a preferred delivery modality. The success of cabotegravir (CAB) as the first generally safe and highly effective long-acting systemic agent for HIV prevention opens up opportunities for the development of an injectable MPT that combines CAB with an effective contraceptive, like levonorgestrel (LNG); LNG has been widely used and has an established safety track record. CONRAD has developed a first-in-class long acting systemic MPT that consists of a bioresorbable injectable depot and that employs a novel drug delivery technology to deliver both CAB and LNG together for at least three months, and possibly longer. Pre-clinical studies in rats and non-human primates show promise. To advance the development of this injectable CAB/LNG MPT our team with complementary expertise will conduct studies to 1) assess the values and preferences for a novel MPT for pregnancy and HIV prevention in adolescent cisgender women (CW) and transgender men (TM) AFAB aged 16-24 years in the USA, using a combination of qualitative interviews and participatory attitudinal ranking approaches to inform the selection of attributes and levels for a Discrete Choice Experiment to be conducted in a sample of 200 CW and 200 TM AFAB; and 2) conduct a multi-site, phase I, single arm PK trial of the CAB/LNG injectable biodegradable depot in a sample of 16 healthy, HIV-negative adolescents and young adults AFAB, ages 18-24, to assess the safety and pharmacokinetic profile of the products in CW and TM AFAB who are receiving gender-affirming hormone therapy. Incorporation of end-user preferences for MPTs early on in product development can enhance acceptability, optimize uptake and use, and ultimately ensure public health benefit. The evaluation of the safety, acceptability and pharmacology of a first in-human CAB/LNG biodegradable depot injection in CW and TM youth will ensure that data on adolescents across genders is available for regulators should co-formulated CAB/LNG move forward for licensure. The availability of a highly effective, long-acting MPT that places a premium on safety and acceptability in adolescents AFAB across genders, has the potential to accelerate access to effective sexual and reproductive health, to potentially address disparities in health access for SGM populations, and to have a substantial impact on the HIV epidemic.

LEN BRIDGE (under an IND)

Lead: Fenway Health, Collaborators: Drs. Hosek, Landowitz and Agwu

PROJECT SUMMARY

Despite the demonstration more than a decade ago that antiretroviral pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV acquisition, its uptake has been suboptimal among American adolescents and young adults (AYA), who have the highest rates of new HIV infections in the US, particularly those from racial and ethnic minority communities. Lenacapavir (LEN) is a first-in-class HIV capsid inhibitor that has demonstrated efficacy in suppressing viremia in individuals with HIV, both naïve and treatment experienced, and is now being tested for use as a PrEP agent. Major advantages of LEN include its ability to be administered as a subcutaneous injection every 6 months, as well as an excellent safety profile in studies to date. We propose to conduct this study within the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN), the only adolescent-focused research network, which is uniquely poised with expertise to oversee and implement this study as well as analyze and disseminate the data to inform regulators and practitioners. This proposal will address a timely and clinically important set of issues, including ensuring adolescent-specific data is available as part of the registrational package for LEN as well as the early identification of adolescent-focused clinical and implementation strategies on how to best deliver LEN to adolescents at-risk for HIV, by addressing the following specific aims: 1) Gather safety, tolerability, acceptability, and pharmacokinetic data on the use of lenacapavir (LEN) long-acting subcutaneous injections for HIV prevention among 60 US cisgender and transgender adolescents under age 18, 2) Examine adherence to, and timeliness of, follow-up injections among adolescent participants who are administered LEN in conjunction with information regarding its safety and efficacy, and 3) Explore the acceptability of, preference for, and choice of available HIV prevention options among cisgender and transgender adolescents.