New long-acting HIV treatment offers hope for drug-resistant infections

A new long-acting HIV treatment could expand options for people who have trouble taking daily pills and whose virus is resistant to some commonly used HIV drugs, according to a new UC San Francisco study.

Unlike daily HIV pills, long-acting treatments can be given weeks or months apart, which can make it easier for people who struggle to take medication every day. The only approved long-acting combination pairs cabotegravir with rilpivirine. But HIV can develop resistance to rilpivirine and related drugs, limiting its use for some people. Moreover, rilpivirine is not available in low- and middle-income countries.

The new approach replaces rilpivirine with lenacapavir, a long-acting drug that attacks HIV in a different way. In the new study, all the participants achieved and maintained control of the virus. 

The findings, published Oct. 8 in JAMA Network Open and funded through the National Institutes of Health, could help address an important gap in long-acting HIV treatment. 

"Clinicians are already starting to use these two drugs together, and until now we've had very little evidence to guide us," said Monica Gandhi, MD, MPH, senior author of the paper and a UCSF professor of Medicine. "This is the largest group studied on this combination, and we think these findings could help providers have more confidence using it."

Researchers at UCSF's Ward 86 HIV Clinic studied 46 people who received long-acting lenacapavir and cabotegravir. Nearly three-quarters had the type of drug resistance that can limit use of the approved combination, and more than half had detectable HIV when they started treatment.

All participants who started with detectable HIV brought the virus under control within 13 weeks, while those who already had it under control stayed that way. After a median follow-up of nearly two years, all participants continued to have undetectable HIV viral loads, the goal of HIV therapy.

The combination is not yet approved as an HIV treatment, and the study did not compare it directly with other treatments. Two clinical trials are planned to study the approach more closely.

But the findings could influence care before those trials are completed. Lenacapavir and cabotegravir are becoming more widely available around the world, including through agreements that allow generic versions in many lower-income countries.