First Long-Acting Injectable Approved for HIV PrEP

The U.S. Food and Drug Administration has approved the first long-acting injectable treatment for HIV preexposure prophylaxis, which is given every two months and offers an alternative to daily oral medication, the agency announced Monday.

Apretude (cabotegravir extended-release injectable suspension) is approved for use in at-risk adults and adolescents who weigh at least 35 kg (77 lb). Patients initiating Apretude begin with two initiation injections administered one month apart and then receive injections every two months after. The FDA notes that patients can start their treatment with Apretude or take oral cabotegravir (Vocabria) for four weeks to assess how well they tolerate Apretude.

The approval was based on safety and efficacy data from two randomized, double-blind trials comparing Apretude to the once-daily oral medication Truvada. The first trial included 4,566 HIV-uninfected men and transgender women who have sex with men and have high-risk behavior for HIV, while the second trial enrolled 3,224 uninfected cisgender women at risk for HIV. Participants randomly assigned to Apretude started with cabotegravir (30-mg tablet) and a placebo daily for up to five weeks, and then at months 1 and 2 and every two months after, they received 600-mg injections of Apretude in addition to a daily placebo tablet. In trials 1 and 2, respectively, researchers found that participants randomly assigned to Apretude had a 69 and 90 percent reduced risk for becoming infected with HIV compared with participants randomly assigned to Truvada.

Side effects occurred more frequently with Apretude than with Truvada and included injection-site reactions, headache, fever, fatigue, back pain, myalgia, and rash. A boxed warning on the Apretude label states that the drug should not be used unless a negative HIV test is confirmed immediately prior to starting the drug and before each injection.

"This injection, given every two months, will be critical to addressing the HIV epidemic in the U.S., including helping high-risk individuals and certain groups where adherence to daily medication has been a major challenge or not a realistic option," Debra Birnkrant, M.D., director of the Division of Antivirals in the FDA Center for Drug Evaluation and Research, said in an agency news release.