PREP step: a stepped care approach for improving PREP adherence among emerging and young adult men in the US - emerging (18-24 years old) and young (25-29 years old) adult men in the U.S. Are at…

The National Institute of Mental Health awarded San Diego State University Research Foundation $736,346 on July 6, 2026, under the Mental Health Research Grants program (CFDA 93.242) to conduct a randomized controlled trial testing a stepped-care intervention to improve pre-exposure prophylaxis (PrEP) adherence among young men ages 18–29 at high risk for HIV infection in the United States.

The PREPSTEP trial will enroll 300 participants on PrEP who face adherence barriers. In the first phase, participants will be randomized 2:1 to receive either an updated PREP IT! mobile application or an information-only control. Those who do not achieve improved PrEP adherence by month 3 will be re-randomized 2:1 to also receive remote ecoaching based on motivational interviewing and cognitive behavioral therapy principles or to continue with the app alone for an additional 6 months, extending total follow-up to 9 months. The intervention builds on a prior pilot study (NIMH R34MH116878) of the PREP IT! mobile app with 80 participants, which demonstrated high retention (>90%) and strong acceptability. The pilot found that participants achieving protective PrEP blood drug levels showed greater engagement than those without protective levels, suggesting differential benefit that the stepped-care approach aims to address.

Work is performed in San Diego, California. The award runs through March 31, 2031.

PREP step: a stepped care approach for improving PREP adherence among emerging and young adult men in the US - emerging (18-24 years old) and young (25-29 years old) adult men in the U.S. Are at high risk for HIV infection. Pre-exposure prophylaxis (PREP) is a highly effective biomedical prevention strategy to reduce HIV transmission and a priority for ending the HIV epidemic in the U.S. However, the effectiveness of PREP depends on achieving protective PREP blood drug levels through optimal adherence behaviors. Mhealth interventions hold promise for delivering timely and tailored PREP adherence support for higher risk communities. Our team was funded (nimh R34MH116878) to develop and pilot test the PREP IT! Mhealth intervention to improve PREP adherence among a national sample (N=80) of 18-29 year old men in the U.S. (mage=25 years; 54% racial/ethnic minority), and we demonstrated high feasibility (>90% retention) and strong acceptability of the intervention. Among participants in the PREP IT! Intervention, those with protective PREP blood drug levels (from dried blood spots) at months 3 and 6 were significantly more engaged in the intervention than those with non-protective PREP drug levels, suggesting benefit for some, but not all, participants. Based on lessons learned of this pilot study, we propose here an RCT to test a stepped-care intervention - called prepstep - to improve protective PREP blood drug levels among 300 18-29 year old men. Participants on PREP and experiencing adherence barriers will be randomized (2:1) to either the updated PREP IT! Mobile APP or an information-only control condition. Those who do not show improvement in PREP adherence at 3-months will be RE-randomized (2:1) to also receive remote ecoaching based on motivational interviewing (MI) and cognitive behavioral therapy (CBT) principles or remain in the PREP IT! APP alone for an additional 6 months, for total follow-up of 9 months. Additionally, we will use this opportunity to include information and tools to encourage uptake and proper use of doxycycline post-exposure prophylaxis (DOXYPEP) to reduce sexually transmitted infections. The proposed study aims are: aim 1: achieve a higher proportion of protective PREP drug blood levels at 6- (primary outcome) and 9-months (secondary outcome) among participants randomized to a novel stepped-care mhealth and ecoaching intervention, called prepstep, compared to an information-only control condition; aim 2: evaluate the components of the prepstep intervention package at months 6 and 9 to characterize: 2A. The effect of receiving the updated PREP IT! Mobile APP alone compared to the control condition; 2B. The additive benefit of receiving ecoaching compared to only receiving the PREP IT! Mobile APP; aim 3: assess acceptability, uptake, and protective coverage of DOXYPEP among participants randomized to prepstep compared to those in the information-only control condition using in-depth interviews and survey results. The proposal has high public health impact by providing a scalable mhealth and ecoaching approach to address gaps in effective PREP adherence interventions to reduce HIV among 18-29 year-old men in the US, as well as the initiation and protective coverage of DOXYPEP. Results of this work will inform a future hybrid type III implementation trial of prepstep more broadly in the US.