ABSTRACT
Kentucky’s HIV epidemic displays an especially profound and disproportionate impact among people who
inject drugs (PWID): 14.8% of males and 54.2% of females newly diagnosed with HIV in 2021 have an
injection drug use-related transmission factor, far exceeding the national average for this exposure category.
A central pillar of Ending the HIV Epidemic (EHE) is the prevention of new HIV infections through scale up of
Pre-Exposure Prophylaxis (PrEP) in key populations, including PWID. For PWID, PrEP uptake remains
severely limited, and no evidence-based PrEP interventions specifically targeted for PWID are available. In our
R34 in KY’s Appalachian region, we successfully implemented two brief, low-intensity interventions to
promote linkage to co-located PrEP care in rural syringe service programs (SSPs), including a newly adapted
strengths-based case management (SBCM-PrEP) intervention designed to address multi-level barriers to
PrEP initiation. Our pilot trial has demonstrated proof of concept for integrated PrEP care within
rurally-located SSPs and high acceptability among PWID: 96% of PWID participants entered the PrEP
care cascade by attending at least one PrEP intervention session, and 86% completed an initial PrEP clinical
visit and point of care testing for PrEP eligibility. Nevertheless, just 51% returned for test results, and 28%
progressed to PrEP prescription, indicating that augmented intervention support is required to optimize PrEP
uptake. Building on this strong foundation, the proposed study will deploy stepped-care adaptive interventions
in three rural SSPs in a Sequential Multiple Assignment Randomized Trial (SMART) design to test the optimal
intervention pathways for PrEP uptake, defined as PrEP initiation (measured by dispensed prescription for oral
PrEP) and persistence in PrEP care (measured by refill verification and biomarker confirmation). The Specific
Aims are to: 1: Compare the relative effectiveness of adaptive interventions (AIs) that begin with Peer-led
SBCM-PrEP versus those that begin with CDC PrEP education plus text messaging (TM) on patient-level PrEP
care outcomes (initiation and persistence) at 1-, 3- and 6-months; 2: Estimate and rank the effectiveness of the
four embedded AIs on PrEP care outcomes at 3- and 6-months: (1) CDC PrEP education, continue TM for
responders, add mobile outreach for non-responders (NR); (2) CDC PrEP education, continue TM for
responders, add peer transitional SBCM for NR; (3) Peer-led SBCM, continue TM for responders, add mobile
outreach for NR; (4) Peer-led SBCM, continue TM for responders, add peer transitional SBCM for NR; and, 3:
Across interventions, examine the effects of age, baseline injection frequency, perceived HIV risk, PrEP
interest, SSP utilization patterns, and other factors, in predicting PrEP care outcomes at 1-, 3- and 6-months to
inform optimally-tailored intervention strategy recommendations for PWID subgroups. Directly informed by our
pilot trial, our SMART design is poised to identify the optimal combination and sequencing of intervention
components required to achieve the greatest likelihood of PrEP initiation.