A new long-acting drug combo can restore control over HIV for patients whose virus has developed resistance to commonly used medications, researchers report.
HIV patients who have trouble taking daily pills can opt for injections of cabotegravir and rilpivirine (Cabenuva), a long-acting treatment that can be given weeks or months apart.
However, HIV can develop resistance to rilpivirine, limiting its use in some patients, researchers noted.
This can be countered by subbing out another drug for rilpivirine, allowing patients to continue with long-term HIV treatment, researchers reported Oct. 8 in JAMA Network Open.
Swapping lenacapavir in place of rilpivirine maintained long-term control over HIV among a small group of patients being treated at the University of California, San Francisco (UCSF), researchers said.
“Clinicians are already starting to use these two drugs together, and until now we’ve had very little evidence to guide us,” senior researcher Dr. Monica Gandhi, a professor of medicine at UCSF, said in a news release.
Lenacapavir is a long-acting drug that attacks HIV in a different way than rilpivirine, researchers said. It disrupts the virus’ protective protein shell, blocking multiple steps in its life cycle, according to Drugs.com.
By comparison, rilpivirine belongs to a class of drugs called nucleoside or nucleotide reverse transcriptase inhibitors (NTRIs), which prevent HIV from copying its RNA into DNA to easily replicate itself.
For the new study, researchers recruited 46 patients being treated at UCSF’s Ward 86 HIV Clinic. Of those patients, nearly three-quarters had developed the type of drug resistance that can limit use of the Cabenuva combo, and more than half had detectable HIV.
The new lenacapavir/cabotegravir combo brought HIV under control within 13 weeks among patients with detectable levels, according to the study.
And after nearly two years, all of the patients continued to have undetectable HIV viral loads, researchers said.
“This is the largest group studied on this combination, and we think these findings could help providers have more confidence using it,” Gandhi said.
The study was funded by a federal grant and was not supported by any pharmaceutical companies, researchers said.
Black Americans remain disproportionately affected by HIV. They make up roughly 12 percent of the U.S. population, yet account for about 39 to 40 percent of new HIV diagnoses and people living with HIV. Higher rates of HIV-related morbidity are often driven by structural barriers rather than biological differences.
Several factors can contribute to virologic failure in Black patients with HIV, including:
Recent findings are promising, as it may offer another option for patients who lose viral suppression because of some of these barriers.
HIV treatment failure can occur for several reasons, including:
For clinicians, individualized regimen selection is critical for preventing HIV treatment failure because it matches the specific biological, clinical, and lifestyle needs of a patient, which directly drives adherence and blocks drug resistance.
Individualized selection can mitigate drug resistance and high genetic barriers, support long-term adherence, avoid adverse effects and toxicity, manage comorbidities and drug interactions, and address social and economic barriers. This is particularly relevant for Black patients with HIV, as they can face barriers to care and achieving viral suppression.
There’s a growing interest in long-acting HIV therapies that can help reduce pill fatigue and improve adherence among patients who struggle with daily treatment regimens. As HIV care continues to evolve, clinicians are increasingly recognizing that treatment isn’t a one-size-fits-all approach, but it requires individualized strategies that account for a patient’s treatment history, resistance profile, lifestyle, and overall health needs.
While these recent findings offer hope for patients who have experienced treatment failure, important questions remain about real-world effectiveness, affordability, and equitable access. These considerations are particularly relevant for Black patients with HIV, who continue to experience disproportionate rates of HIV infection and face persistent barriers to achieving optimal health outcomes.
More information
The Mayo Clinic has more on treating HIV.
SOURCE: University of California, San Francisco, news release, Oct. 8, 2026
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