Long-lasting, injectable HIV prevention drug set for “aggressive” roll-out in Africa

Tools to fight HIV tend to come late to sub-Saharan Africa, the region hardest hit by the epidemic. After powerful, lifesaving cocktails of HIV drugs came to market in 1996, it took 7 years before they began to reach large numbers of people living with the virus there. When pills to prevent, rather than treat, HIV infection were introduced in 2012—a strategy known as pre-exposure prophylaxis (PrEP)—Africa was again slow to benefit.

One of many clinics in the long-running SEARCH study in Kenya, which recruited people to test a long-acting, injectable HIV-prevention drug

But with the next revolution in HIV prevention—an injectable, long-lasting version of PrEP—Africans may actually soon lead the pack. Not many people in rich countries have started to take this formulation, mainly because of insurance hassles for the expensive drug. But injectable PrEP is now on the cusp of being widely introduced in Africa, thanks to the President’s Emergency Plan for AIDS Relief (PEPFAR), a U.S. government program, which has purchased it at a steep discount.

“Over the next 2 years, we will see more injectable PrEP use in East and Southern Africa than we’ll see in the U.S.,” predicts Mitchell Warren, who heads AVAC, an advocacy group for HIV prevention. “That’s turning history on its head.”

PEPFAR had provided 24,000 doses of injectable PrEP in Zambia, Zimbabwe, and Malawi by 6 March and has plans for an “aggressive scale-up,” says PEPFAR head John Nkengasong. The drug has “the potential to bend the curve on the annual 1.3 million new HIV infections globally,” Nkengasong says, but the availability and cost of injectable PrEP “are still a big concern” and could limit its impact. (PEPFAR’s own future funding has been in limbo, but congressional negotiators last week agreed to extend it through March 2025.)

PrEP first proved its worth as daily pills made by Gilead, but they only work if people take them consistently—which many find difficult to do. The long-acting, injectable version of PrEP, made by the pharmaceutical company ViiV Healthcare, contains the antiviral cabotegravir (CAB-LA); a shot once every 2 months suffices. Big international trials that included participants in Africa showed the drug to be more effective than oral PrEP in men who have sex with men and transgender women and, separately, in women. The U.S. Food and Drug Administration approved CAB-LA in December 2021, and the European Commission authorized it in September 2023. Other long-acting injectables that last 4 or even 6 months are now being tested.

But in the United States, CAB-LA costs more than $23,000 annually for the 2-month shots. Patients and health care providers have had trouble getting their health insurers to pay for injections, in part because PrEP pills, now available from generic companies, cost as little as $300 per year. As a result, only 11,000 people in the U.S. had started to use CAB-LA by the end of 2023, ViiV says.

ViiV was assailed by activists in 2022 for not making inexpensive versions of CAB-LA available in Africa, but the company has stressed it is committed to selling CAB-LA at “a nonprofit price” in low-income countries until a generic version is available. “We seek to make our medicines widely available to those who need it—regardless of income or where they live, driven by public health needs,” ViiV said in a statement to Science. PEPFAR pays $30 per 2-month dose, or $180 per year. There is also PrEP in a vaginal ring version that works for 1 month and costs PEPFAR $13 each.

A study in Uganda and Kenya, presented at a U.S. HIV/AIDS conference this month, suggested that given the choice, people at risk of HIV chose CAB-LA over oral PrEP—but simply having options increased PrEP use overall. “There is much interest in injectable PrEP,” says Moses Kamya, an epidemiologist at Makerere University who presented the findings. It’s “not just replacing oral PrEP,” he adds. “It expands the pie.”

ViiV will have at least 1.2 million doses of CAB-LA available for low- and middle-income countries through 2025, and about 30% of those will go to PEPFAR. But so far, not a single country in sub-Saharan Africa has put in an order to purchase the drug with its own money, says Linda-Gail Bekker, who runs the Desmond Tutu HIV Centre at the University of Cape Town. In South Africa—which has the world’s highest number of people living with HIV and purchases more oral PrEP than any country—an investment analysis published in December 2023 concluded CAB-LA would not be cost effective, even at its discounted price. “The modelers have figured that the bang is not worth the buck,” Bekker says. She’s heartened that at least PEPFAR will soon start to offer CAB-LA in South Africa.

For mass introduction, she and others say, the price will need to come down further. ViiV has signed a voluntary licensing agreement with the Medicines Patent Pool that makes it possible to cut deals with companies that can produce the drug more cheaply. Three generics manufacturers have licensed the drug, but Warren estimates it will take at least 2 years before they can deliver. The generics must first be shown to work as well as ViiV’s drug, and they are unlikely to be as cheap as pills, because injectable PrEP is more complicated to manufacture.

Warren is optimistic that if injectable PrEP is accessible in Africa, it will eventually become popular, but he stresses that PrEP pills and vaginal rings still have their place as well. “There’s no such thing as ‘better’ PrEP,” Warren says. “Each one is different. Now you can say: ‘Let’s talk about these different options.’”

Source: science