Long-acting injectable antiretrovirals can be an effective treatment or prevention option for homeless and unstably housed people living with or at risk for HIV, according to results from a San Francisco pilot study published in the Journal of Acquired Immune Deficiency Syndromes.

“The implementation of long-acting antiretrovirals is feasible in low-barrier, highly supportive clinical settings serving vulnerable people experiencing homelessness,” the study authors concluded. “If effective scale-up is possible, HIV disparities may be markedly reduced, which will be critical in progressing toward national goals to end the HIV epidemic.”

All modern antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) regimens are safe and effective, so success often comes down to consistent use. But some people have trouble maintaining good adherence because they forget to take pills every day, are concerned about having pill bottles that could reveal their HIV status or are living in situations where their meds could be lost or stolen. About a third of people diagnosed with HIV in the United States have not achieved viral suppression, which means they are at risk for disease progression and could transmit the virus to others.

For some individuals, long-acting injectable treatment or PrEP may be a better option. Approved in 2021, Cabenuva (long-acting cabotegravir and rilpivirine) is the first complete antiretroviral regimen that does not require daily pills. It involves two injections administered by a health care provider once monthly or every other month. Injectable cabotegravir alone, sold as Apretude, is the longest-acting approved PrEP option. An even longer-acting drug, lenacapavir (Sunlenca), which is approved for people with multidrug-resistant HIV and shows great promise for PrEP, is administered once every six months.

Studies have shown that Cabenuva works as well as oral antiretrovirals for treatment-experienced people and those starting ART for the first time. Apretude was found to be even more effective than daily PrEP pills, largely because it encourages better adherence. Cabenuva is currently approved only for people who have achieved an undetectable viral load on an oral regimen, but studies have shown that it can also be a good option for people without viral suppression if they receive adequate support.

Nicky Mehtani, MD MPH, of the University of California San Francisco, and colleagues evaluated the feasibility and effectiveness of long-acting antiretrovirals for people who use drugs and people experiencing homelessness who face disproportionate structural and psychosocial barriers in adhering to daily oral ART or PrEP.

This pilot study included 33 homeless or unstably housed people who started long-acting ART or PrEP at the Maria X. Martinez Health Resource Center between November 2021 and November 2023. Part of the San Francisco Department of Public Health’s Whole Person Integrated Care program, the clinic provides low-barrier primary and urgent care for people experiencing homelessness. Services are provided on a drop-in basis six days a week at an accessible location near the Tenderloin district. In addition, the clinic works with satellite sites and street medicine teams to deliver injections at other locations, such as syringe access programs, homeless shelters, tent encampments and a local jail.

Just over half of the participants were cisgender men, 27% were transgender women or nonbinary individuals and 18% were cisgender women. The median age was 37 years. Nearly half (45%) were Black, followed by multiracial/other (30%), white (27%) and Latino (21%) people. Seventeen (52%) were staying at shelters or other nonpermanent residences, nine (27%) were living on the street and seven (27%) lacked stable housing. Most used drugs—primarily methamphetamine—and about 60% had a history of injection drug use. Nearly two thirds reported depression or posttraumatic stress disorder, and 18% each reported schizophrenia or bipolar disorder. Most were insured by California’s Medicaid program, which fully covers the cost of injectable antiretrovirals.

“[T]he motivation for implementing this long-acting injectable program at [Maria X. Martinez] has always been pretty simple: to improve clinical outcomes for some of our most vulnerable patients [living] with and at risk for HIV,” Mehtani told POZ. “The majority of our patients struggle with taking daily oral medications—whether for HIV treatment or PrEP, mental health treatment or other medical conditions. In the case of HIV, it’s particularly difficult to witness patients’ health physically deteriorate over time as a result of their not being able to take oral ART ​for reasons related to lack of safe medication storage, food insecurity and competing demands in the face of poverty.”

The program’s treatment and PrEP protocols were adapted from guidelines developed by Ward 86 at San Francisco General Hospital, which has demonstrated the feasibility of long-acting therapy for a marginalized population. Most of the 18 people living with HIV received Cabenuva, but four used injectable cabotegravir plus lenacapavir due to rilpivirine resistance. Fourteen had a detectable viral load, including eight who had never previously achieved viral suppression. A third had advanced immune deficiency with a CD4 count below 200. All 15 HIV-negative people started Apretude for PrEP.

The long-acting antiretrovirals proved highly effective. All but one of the HIV-positive people achieved or maintained viral suppression over an average follow-up period of about 10 months, and all of the participants on PrEP remained HIV negative over an average five months of follow-up. Adherence was good in both groups: Of the 224 injections administered, just 8% were delayed more than a week.

“While I’d be the first to admit that there are risks associated with offering long-acting injectable ART within low-barrier settings like ours, when the alternative is that patients physically cannot take oral ART and are likely to die without treatment, the benefits of offering these novel treatments do outweigh the potential risks,” Mehtani said. “Several patients have had dramatic improvements in CD4 counts, adding years to their lives, which would have not been possible without their receiving long-acting injectable ART.”

“However, running this program has required robust multidisciplinary support and a clear understanding of protocols—not only by prescribing providers, but by the entire clinic staff as well as by any patients considering initiating these medications,” she added. “It has been a team effort and collaborative mindset that has made this work.”

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