Delivering Long-Acting Injectable Cabotegravir PrEP to People Experiencing Homelessness and People Who Use Drugs

Long-acting injectable cabotegravir (CAB-LA) may be particularly advantageous for preventing HIV among people experiencing homelessness (PEH) and people who use drugs (PWUD), populations at high HIV risk with poor oral pre-exposure prophylaxis (PrEP) outcomes. In a retrospective study using the RE-AIM framework to organize programmatic outcomes, we evaluated real-world implementation of CAB-LA at the Maria X. Martinez Health Resource Center, a status-neutral, fully drop-in municipal clinic in San Francisco, CA, serving >4000 patients annually for diverse health needs. We included all patients prescribed CAB-LA between October 2022 and December 2025. Outcomes included reach, adoption, implementation (injection timeliness, delivery setting, guideline-concordant HIV monitoring), maintenance (retention), and exploratory effectiveness (HIV acquisitions relative to active coverage). Nineteen providers prescribed CAB-LA to 68 patients (63% experiencing homelessness; 56% with stimulant use disorder, 34% opioid use disorder, 51% psychotic-spectrum illness); 52 (76%) received ≥1 injection. Of 304 injections, 42% occurred outside the clinic, including in shelters, on the street, and in jail or inpatient settings; 76% of follow-up injections were on time. HIV testing concordant with the Centers for Disease Control and Prevention guidelines (antigen/antibody plus RNA) accompanied 37% of injections. Twelve-month retention was 49%. Two patients acquired HIV, both during gaps in CAB-LA coverage. Sustaining coverage required intensive outreach, population tracking, insurance reenrollment, and financial incentives. Findings suggest that CAB-LA can be delivered in a fully drop-in clinic serving PEH and PWUD, while highlighting the resource-intensive support required to maintain coverage. Adapting delivery models, laboratory monitoring protocols, and financing to the realities of structurally vulnerable populations is essential to extend the benefits of long-acting PrEP.