Apretude, the New Tool in the HIV Prevention Toolkit

There is significant unmet need in HIV prevention, with less than 1 in 4 of the 1.2 million people who could benefit from re-exposure prophylaxis (PrEP) in the U.S. currently taking it despite its wide availability.

The approval of Apretude (cabotegravir) might change that projection because it is the first long-acting injectable option to reduce the risk of sexually acquired HIV, notes an executive at ViiV Healthcare, which developed the medication.

“In addition to demonstrating superior efficacy to a daily oral PrEP option (FTC/TDF tablets) in clinical trials, Apretude is also given as few as six times per year, as opposed to oral daily PrEP options, which require 365 days of dosing,” says Alex Rinehart, Ph.D., medicines development leader, prevention for ViiV Healthcare. “There is a need for new tools to end the HIV epidemic, and long-acting medicines like Apretude, which significantly reduces frequency of dosing without the need to take a daily pill, can play a crucial role in helping to reduce new cases of HIV.”

“Many people who are vulnerable to HIV live complex lives that can make taking a daily pill to prevent HIV a burden,” adds Rinehart. “These individuals might encounter stigma, fears about accidental disclosure of their medicine, as well as general complications from daily living.”

Apretude is an integrase strand inhibitor (INSTI), explains Rinehart. INSTIs inhibit HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic disease.

The long-acting injectable formulation of cabotegravir has a long half-life, which allows the medicine to stay in the body for longer, so it can be taken less frequently.

The FDA approval of Apretude in December 2021 was based on the results from two, international phase IIb/III multicenter, randomized, double-blind, active-controlled trials, which evaluated the safety and efficacy of Apretude in HIV-negative men and transgender women who have sex with men (HPTN 083) and cisgender women (HPTN 084), who were at increased risk of sexually acquiring HIV.

These trials, which included more than 7,700 participants across 13 countries combined, were stopped early by an independent data safety monitoring board after Apretude was shown to be superior to daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) tablets in preventing the acquisition of HIV in study participants.

“Clinical trial participants who received Apretude experienced a 69% lower incidence of HIV compared to FTC/TDF tablets in HPTN 083 and a 90% lower incidence of HIV compared to FTC/TDF tablets in HPTN 084,” Rinehart says. “Apretude was studied in one of the most diverse and comprehensive HIV prevention trials to date, which included some of the largest numbers of transgender women and Black men who have sex with men ever enrolled in an HIV prevention trial.”