Long-acting injectable antiretrovirals can be a feasible treatment or prevention option for homeless and unstably housed people who have trouble using daily pills. A pilot study looked at 33 people who started HIV treatment or pre-exposure prophylaxis (PrEP) at the Maria X. Martinez Health Resource Center in San Francisco, which provides low-barrier care augmented by satellite sites and street medicine teams that deliver injections at syringe access programs, shelters and tent encampments. Most used drugs, primarily methamphetamine, and mental health problems were common. Of the 18 people with HIV—including 14 with a detectable viral load—most received Cabenuva (long-acting cabotegravir and rilpivirine) monthly or every other month, but four used injectable cabotegravir plus lenacapavir. All but one achieved or maintained viral suppression. In addition, 15 people started Apretude (injectable cabotegravir alone) for PrEP. All remained HIV negative. Adherence was good, with just 8% of scheduled injections delayed more than a week.