New Long-Acting HIV Pairing Shows Promise for People With Drug Resistance

People living with HIV who have trouble taking a pill every day, and whose virus has become resistant to some common HIV drugs, may have a new long-acting treatment option, according to a study published in JAMA Network Open from the University of California, San Francisco (UCSF).

All 46 people who received a combination of two long-acting drugs, lenacapavir and cabotegravir, brought the virus under control or kept it controlled, and they stayed that way for nearly two years.

A gap in long-acting HIV treatment

Daily HIV pills work well when people take them consistently. But for some, taking medication every day is hard to keep up. Long-acting treatments are injections given weeks or months apart, which can make it easier to stay on therapy.

Only one long-acting combination is currently approved: cabotegravir with rilpivirine, which first won approval in 2021. HIV can develop resistance to rilpivirine and related drugs, which limits who can use it. Rilpivirine is also not available in many low- and middle-income countries.

Swapping in a drug that works differently

The new approach replaces rilpivirine with lenacapavir. Lenacapavir was approved in 2022 for HIV that is resistant to multiple drugs. It is the first of a class called capsid inhibitors, which attack the virus in a different way from older medications.

“Clinicians are already starting to use these two drugs together, and until now we’ve had very little evidence to guide us,” said senior investigator Monica Gandhi, M.D., M.P.H., a professor of medicine at UCSF. “This is the largest group studied on this combination, and we think these findings could help providers have more confidence using it.”

Who was treated at Ward 86

Researchers reviewed medical records for patients who started the combination at UCSF’s Ward 86 HIV Clinic between March 2023 and May 2025, and followed them through November 2025. Participants averaged 47 years old. About 70% were men, 24% were women and 7% were gender diverse. Roughly 35% were Black, 35% were Hispanic or Latino, and 24% were White.

Many faced serious treatment challenges. Nearly three-quarters (72%) had the type of drug resistance that can limit use of the approved long-acting combination. More than half (52%) had detectable HIV when they started. Of those, more than half had CD4 counts of 200 cells or fewer, a sign of a significantly weakened immune system. About 37% of patients also received rilpivirine as part of their regimen.

Viral control across nearly 2 years

Every patient who started with detectable HIV reached viral suppression within 13 weeks. Patients who were already suppressed stayed that way.

After a median follow-up of 100 weeks, all participants remained suppressed. No patient had two viral load tests in a row above 200 copies per milliliter, the threshold the study used to define viral suppression.

Important limits on the findings

The combination is not approved as an HIV treatment. The study looked back at records from a single clinic and did not compare the regimen directly with other treatments. Ward 86 also has a dedicated team and support system for its long-acting program, so results may differ in other settings. Two clinical trials are planned to study the approach more closely.