By IDSE News Staff
The FDA approved cabotegravir (CAB) extended-release injectable suspension (Apretude, ViiV Healthcare) for use in at-risk adults and adolescents weighing at least 35 kg for preexposure prophylaxis (PrEP) to reduce the risk for sexually acquired HIV.
Injectable CAB is given initially as two injections administered one month apart, and then every two months thereafter. Patients can either start their treatment with injectable CAB or take oral CAB (Vocabria, ViiV) for four weeks to assess how well they tolerate the drug.
The safety and efficacy of the injectable CAB to reduce the risk for acquiring HIV were evaluated in two in-ternational phase 2b/3, randomized, double-blind, active-control trials, HPTN 083 and HPTN 084, which compared injectable CAB with emtricitabine-tenofovir disoproxil fumarate (FTC/TDF; Truvada, Gilead) a once-daily oral medication for HIV PrEP.
Trial 1 included HIV-uninfected men and transgender women who have sex with men and have high-risk behavior for HIV infection. Trial 2 included uninfected cisgender women at risk for acquiring HIV.
Participants who took injectable CAB started the trial with oral CAB (30-mg tablet) and placebo daily for up to five weeks, followed by a CAB 600-mg injection at months 1 and 2, then every two months thereafter and a daily placebo tablet.
Participants who took FTC/TDF started the trial taking oral FTC/TDF and placebo daily for up to five weeks, followed by oral FTC/TDF daily and placebo intramuscular injection at months 1 and 2, and every two months thereafter.
In Trial 1, 4,566 cisgender men and transgender women who have sex with men received either injectable CAB or FTC/TDF. The trial measured the rate of HIV infections among trial participants taking daily CAB fol-lowed by CAB injections every two months compared with daily oral FTC/TDF. The trial showed participants who took CAB had 69% less risk for getting infected with HIV when compared with participants who took FTC/TDF.
In Trial 2, 3,224 cisgender women received either injectable CAB or FTC/TDF. The trial measured the rate of HIV infections in participants who took oral and injections of CAB compared with those who took FTC/TDF orally. The trial showed participants who took injectable CAB had 90% less risk for getting infected with HIV when compared with participants who took FTC/TDF.
“People who are vulnerable to acquiring HIV, especially those in Black and Latinx communities who are disproportionately impacted in the US, may want options beyond daily oral pills. That’s why ViiV Healthcare is proud that Apretude was studied in one of the most diverse and comprehensive HIV prevention trial programs to date, which also included some of the largest numbers of transgender women and Black men who have sex with men ever enrolled in an HIV prevention trial. With Apretude, people can reduce the risk of acquiring HIV with as few as six injections a year,” said Deborah Waterhouse, CEO of ViiV Healthcare.
According to the CDC, notable gains have been made in increasing PrEP use for HIV prevention in the United States, and preliminary data show that in 2020, about 25% of the 1.2 million people for whom PrEP is recommended were prescribed it, compared with only about 3% in 2015. However, there remains signifi-cant room for improvement.
“We have the tools to end the HIV epidemic through the implementation of effective antiretroviral treat-ment and HIV prevention. PrEP has played a vital role in protecting people from acquiring HIV. With the availability of cabotegravir long-acting for PrEP as an injection every two months to prevent HIV, people now have an important new option besides daily medication. This long-acting medication offers more options for prevention, and now providers and patients will be empowered by choices and the ability to choose the ap-proach that is optimal for each individual,” said Richard Elion, MD, the director of research at the Washington Health Institute.
PrEP requires high levels of adherence to be effective, and certain high-risk individuals and groups, such as young men who have sex with men, are less likely to adhere to daily medication. Other interpersonal fac-tors, such as substance use disorders, depression, poverty and efforts to conceal medication, also can affect adherence. It is hoped that the availability of a long-acting injectable PrEP option will increase PrEP uptake and adherence in these groups.
Side effects occurring more frequently in participants who received injectable CAB compared with those who received FTC/TDF in either trial include injection site reactions, headache, pyrexia (fever), fatigue, back pain, myalgia and rash. For full prescribing information, click here.
Injectable CAB includes a boxed warning to 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 for developing drug resistance. Drug-resistant HIV variants have been identified in people with undiagnosed HIV when they use injectable CAB for HIV PrEP.
Individuals who become infected with HIV while receiving injectable CAB for PrEP must transition to a complete HIV treatment regimen. The drug labeling also includes warnings and precautions regarding hy-persensitivity reactions, hepatotoxicity and depressive disorders.
Injectable CAB was granted a priority review and breakthrough therapy designation.
