FDA approves long-acting injectable PrEP

  • by Liz Highleyman, BAR Contributor
  • Tuesday December 21, 2021
Share this Post:
The federal Food and Drug Administration has approved Apretude, the first long-acting injectable option for HIV prevention. Photo: Courtesy ViiV Healthcare
The federal Food and Drug Administration has approved Apretude, the first long-acting injectable option for HIV prevention. Photo: Courtesy ViiV Healthcare

The federal Food and Drug Administration has approved Apretude (extended-release cabotegravir), the first long-acting injectable option for HIV prevention. The shots, which are administered by a health care provider every two months, were more effective than daily PrEP pills in two large studies of gay men, trans women, and cisgender women.

"The FDA approval of long-acting injectable cabotegravir is a major breakthrough for the prevention field," Dr. Susan Buchbinder, director of Bridge HIV at the San Francisco Department of Public Health, said in a statement from the International AIDS Society. "Some people aren't able to, or don't want to, take PrEP pills. This will give people a new, discreet option for getting PrEP without needing to worry about daily adherence."

Apretude, from ViiV Healthcare, was approved December 20 for adults and adolescents weighing at least 77 pounds. It involves a single injection in the buttocks every other month, after a lead-in of two once-monthly shots or a month of cabotegravir pills. The every-other-month injections can be given within a seven-day window before or after the scheduled dose. If a person misses an injection by more than a week, they can substitute daily cabotegravir pills for up to two months.

This works out to six clinic visits per year, which some people may find more convenient than taking Truvada (tenofovir disoproxil fumarate/emtricitabine) or Descovy (tenofovir alafenamide/emtricitabine) pills every day or taking Truvada "on demand" before and after sex. The shots may lead to better adherence for people who find it difficult to take pills consistently, do not want to have pill bottles that could reveal they're at risk for HIV, or are worried about their pills being lost or stolen.

"Today's approval adds an important tool in the effort to end the HIV epidemic by providing the first option to prevent HIV that does not involve taking a daily pill," Dr. Debra Birnkrant of the FDA's Center for Drug Evaluation and Research said in a statement. "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."

More effective than Truvada

Apretude is approved for cisgender and transgender men and women with no limitations based on the type of sex they have. Truvada PrEP is also approved across the board, but Descovy PrEP is not approved for cisgender women or other people exposed to HIV via vaginal sex because clinical trials did not include this population.

One of the large Apretude trials enrolled more than 4,000 gay and bisexual men and transgender women who have sex with men in the United States, Latin America, Asia, and Africa. The other enrolled more than 3,000 cisgender women in Africa. Although the studies did not include trans men, they are still eligible to use the PrEP injections.

Participants in both studies were randomly assigned to receive cabotegravir injections every two months or once-daily Truvada. The study of gay men and trans women was halted ahead of schedule in May 2020 after an early analysis showed that Apretude worked at least as well as daily pills. Further results showed that the injections were 69% more effective at preventing HIV acquisition — a remarkable finding, given that daily Truvada itself reduces the risk by about 99% for gay and bi men who use it consistently.

The African women's study was also stopped early after an interim analysis found that the injections were more effective than Truvada. Final results showed that women who used Apretude had about a 90% lower risk of acquiring HIV than those who used daily pills. The greater effectiveness of Apretude appears to be attributable to better adherence.

In both studies, Apretude was safe and well tolerated. The most common side effect is injection site reactions such as pain, redness, or swelling. These are usually mild or moderate and last only a few days. While most trial participants reported such reactions, few stopped the injections for this reason.

Apretude must not be used by people who already have HIV, as this can lead to the emergence of drug-resistant virus. The prescribing information includes a warning not to use it without a confirmed negative HIV test immediately prior to starting the drug and before each subsequent injection. People who acquire HIV despite using Apretude should transition to a complete combination treatment regimen. Injectable cabotegravir is also a component of Cabenuva, the only complete long-acting regimen for HIV treatment.

Cost and access

An estimated 34,800 new cases of HIV were reported in the United States in 2019 and there were 168 new cases in San Francisco in 2020, according to the latest HIV epidemiology report from the city's Department of Public Health. The federal Centers for Disease Control and Prevention estimates that only about a quarter of the 1.2 million people who could benefit from PrEP have received a prescription for it.

In anticipation of its approval, Apretude was included in the CDC's updated PrEP guidelines, released earlier this month, which state that clinicians should offer PrEP to anyone who requests it.

Different people have different needs and preferences, and experts hope having more prevention options available will increase PrEP uptake.

"Psychologically, PrEP offers an HIV-negative person a sense of agency over their HIV status, and a way to enjoy sex without fear," Damon Jacobs, founder of the PrEP Facts Facebook group, told the Bay Area Reporter. "Injectable PrEP offers a new option for people to feel proactive, responsible, and empowered about their sexual pleasure and protection."

But limited access to the new prevention option could prove to be a barrier. Offering the shots may impose an additional burden on HIV providers, especially in the context of reduced services due to COVID-19.

At a wholesale cost of $3,700 per dose, Apretude will cost about the same as two months worth of brand-name Truvada or Descovy, but substantially more than generic tenofovir disoproxil fumarate/emtricitabine. It is not yet clear whether the federal rule that requires most insurers to cover PrEP pills will also apply to PrEP injections. ViiV's approval announcement did not state whether the company would offer a co-pay card to reduce out-of-pocket expenses or a patient assistance program for those without insurance.

Advocates also stress the need for global access to Apretude.

"The approval of [injectable cabotegravir] is a vital shot in the arm for HIV prevention," said Mitchell Warren, executive director of AVAC. "With as few as six shots per year, this highly effective form of injectable PrEP can help bend the curve of the HIV epidemic — but only if its approval is accompanied by strategic, effective, and equitable rollout that transforms the growing list of HIV prevention options into real and accessible choices for the people who need prevention most."

Help keep the Bay Area Reporter going in these tough times. To support local, independent, LGBTQ journalism, consider becoming a BAR member.