The FDA approved an extended-release injectable version of cabotegravir (Apretude) as pre-exposure prophylaxis (PrEP) for adults and adolescents weighing at least 35 kg (77 lbs) who are at risk for sexually acquired human immunodeficiency virus (HIV).
The prophylactic drug—administered as two injections one month apart at treatment initiation, followed by a single injection every two months thereafter—will potentially be an important tool for individuals at risk for HIV infection who have difficulty sticking to a daily pill regimen, the FDA explained in a press release. With this indication, patients can either start on the injectable version right away or take oral cabotegravir for four weeks to assess tolerability.
“According to the U.S. Centers for Disease Control and Prevention, notable gains have been made in increasing PrEP use for HIV prevention in the U.S. and preliminary data show that in 2020, about 25% of the 1.2 million people for whom PrEP is recommended were prescribed it, compared to only about 3% in 2015,” the agency explained. “However, there remains significant room for improvement. PrEP requires high levels of adherence to be effective and certain high-risk individuals and groups… are less likely to adhere to daily medication. Other interpersonal factors, such as substance use disorders, depression, poverty, and efforts to conceal medication also can impact adherence. It is hoped that the availability of a long-acting injectable PrEP option will increase PrEP uptake and adherence in these groups,” wrote the FDA.
This approval was based on results from a pair of randomized, double-blind trials that pitted the injection against once-daily oral tenofovir in at-risk patients who had not developed HIV.
In the first trial, which was previously reported by BreakingMED, researchers randomized a cohort of 4,566 cisgender men and transgender women to either cabotegravir or tenofovir.
“The trial measured the rate of HIV infections among trial participants taking daily [oral] cabotegravir followed by [cabotegravir] injections every two months compared to daily oral [tenofovir],” the FDA explained. “The trial showed participants who took cabotegravir] had 69% less risk of getting infected with HIV when compared to participants who took [tenofovir].”
In the second trial, researchers tested the same treatments in a cohort of 3,224 cisgender women. In that trial, participants who took injectable cabotegravir “had 90% less risk of getting infected with HIV when compared to participants who took [tenofovir].”
The most frequently reported side effects with injectable cabotegravir in these trials included injection site reactions, headache, fever, fatigue, back pain, myalgia, and rash. The drug’s label also includes a boxed warning that patients should not use the drug unless a negative HIV test is confirmed.
“It must only be prescribed to individuals confirmed to be HIV-negative immediately prior to starting the drug and before each injection to reduce the risk of developing drug resistance,” the FDA warned. “Drug-resistant HIV variants have been identified in people with undiagnosed HIV when they use [injectable cabotegravir] for HIV PrEeP. Individuals who become infected with HIV while receiving [cabotegravir] for PrEP must transition to a complete HIV treatment regimen. The drug labeling also includes warnings and precautions regarding hypersensitivity reactions, hepatotoxicity, and depressive disorders.”
Injectable cabotegravir is manufactured by ViiV.
John McKenna, Associate Editor, BreakingMED™
Cat ID: 339
Topic ID: 338,339,339,730,27,192,151,725,925