Dr. Hojilla's long-term career goal is to become an independently funded investigator with expertise in
HIV prevention and precision behavioral interventions to optimize biomedical prevention strategies, like pre-
exposure prophylaxis (PrEP), in populations with substance use (SU). PrEP is a key pillar of the Ending the
Epidemic Initiative and although uptake is increasing, the high rates of PrEP discontinuation threaten its public
health impact. SU, including drug and unhealthy alcohol use, are well-established predictors of HIV risk and
presents an overlapping vulnerability for poor adherence and poor retention in care. Early PrEP discontinuation
is a key predictor of subsequent HIV infection, but few persistence interventions exist, particularly for
individuals with SU. Differentiated interventions, where efforts are adapted based on individual needs, have
shown promising findings in the HIV treatment literature, but have not been evaluated in the context of PrEP.
Using the ADAPT-ITT framework, the overall objective of this K23 application is to adapt existing evidence-
based adherence strategies to develop differentiated PrEP persistence interventions in populations with SU.
The study will leverage a large, clinic-based cohort of PrEP patients in Kaiser Permanente Northern California
(KPNC), an integrated healthcare delivery system. Aim 1 will estimate individual growth trajectories to identify
latent patterns (classes) of PrEP persistence. We will evaluate predictors of each class and compare
differences in patterns of PrEP use between patients with and without SU. Understanding the patterns by
which patients use PrEP over time and the characteristics that predict problematic patterns of PrEP use will
allow us to distinguish individuals who require intervention and evaluate what interventions will work best for a
given subgroup. In Aim 2, patients with SU from the two persistence classes with the highest rates of PrEP
discontinuation will be selected for qualitative interviews to examine intervention preferences and barriers and
facilitators of sustained PrEP use within each subgroup. Clinician stakeholders will also be interviewed to
assess capacity to provide differentiated interventions. In Aim 3, evidence-based adherence strategies will be
identified and adapted based on qualitative insights from Aim 2. An intervention protocol will be developed,
iteratively revised with input from topical experts, and piloted to assess feasibility and acceptability. Findings
will inform the development of a future efficacy trial. The proposed research and training plan will provide Dr.
Hojilla with the necessary skillset to achieve his long-term career goal. He will gain training in 1) advanced
quantitative analytical approaches to estimate longitudinal growth trajectories; 2) qualitative research methods
to understand stakeholder needs; and 3) intervention adaptation to develop tailored strategies. He will be
supported by a multidisciplinary team of mentors at the University of California, San Francisco (UCSF) and the
KPNC Division of Research. Dr. Hojilla's training will prepare him to lead high-impact research evaluating
precision behavioral interventions to optimize HIV prevention strategies, such as PrEP, in populations with SU.