Long-Acting Lenacapavir and Cabotegravir Sustain HIV Suppression in Case Series

Treatment-experienced people with HIV who initiated long-acting lenacapavir and cabotegravir achieved and sustained viral suppression, according to a retrospective case series published in JAMA Network Open. The investigators described the 46-patient cohort as, to their knowledge, the largest case series of the combination to date.

Long-acting cabotegravir plus rilpivirine is the only approved long-acting combination regimen, but rilpivirine has a low genetic barrier to resistance, the authors noted. Lenacapavir, a first-in-class HIV capsid inhibitor, was approved for multidrug-resistant HIV in 2022, and clinicians are increasingly pairing it with other long-acting agents despite limited effectiveness data, they wrote.

Investigators at the University of California, San Francisco, reviewed records from the Ward 86 HIV Clinic, a Ryan White Program–funded site, for patients who initiated long-acting lenacapavir from March 2023 through May 2025. Baseline nonnucleoside reverse transcriptase inhibitor resistance was present in 71.7% of patients, and 37.0% received rilpivirine as part of the regimen. At initiation, 22 patients (47.8%) had viral suppression (HIV RNA <200 copies/mL), and 24 (52.2%) were viremic. Patients with baseline suppression maintained it, and all patients viremic at baseline achieved suppression by 13 weeks.

Over a median follow-up of 100 weeks (IQR, 63-131 weeks) from the first lenacapavir injection, no patient had consecutive viral loads above 200 copies/mL. Of the 24 viremic patients, 58.3% had CD4+ counts of 200 cells/mm³ or fewer; across the cohort, 41.3% had unstable housing. Injection site reactions were documented in 58.7% of patients.

The authors cited the retrospective design, sample size, and single-center setting as limitations, noting that Ryan White–funded clinics have higher viral suppression rates than the US national average (91.4% vs 67.2%) and infrastructure that may limit generalizability. They concluded that the findings add to growing evidence supporting long-acting lenacapavir and cabotegravir for patients with adherence challenges and resistance. Two trials are planned in the Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections clinical trials network, according to the authors.

Source: Gistand NL, Mishra IC, Hunter K, et al. Long-acting lenacapavir and cabotegravir and viral suppression among people with HIV. JAMA Netw Open. 2026;9(10):e2638182. doi:10.1001/jamanetworkopen.2026.38182