KAMPALA, UGANDA—Melb Simiyu, an HIV prevention officer at a support organization for sex workers here, says most of her clients have asked when a drug called CAB-LA will become available. Approved by the U.S. Food and Drug Administration (FDA) in December 2021, the HIV prevention drug could drastically reduce infections among marginalized groups like the one she works with.
But even though a trial in Uganda and six other sub-Saharan African countries provided data key for FDA’s approval, Africa, still the part of the world hardest hit by HIV, may face a long wait to get the drug at an affordable price.
On 27 May, CAB-LA’s developer, Viiv Healthcare, made a formal commitment to issue a voluntary license for the drug, an injectable form of pre-exposure prophylaxis (PrEP), to the Geneva-based Medicines Patent Pool (MPP). If the two reach an agreement, MPP could broker deals with generic manufacturers to produce cheap versions of CAB-LA for low- and middle-income countries. But it may take years before those generics become available, and activists accuse Viiv of dragging its feet, which the company denies. Zambian HIV activist Kenly Sikwese, who coordinates the African Community Advisory Board, says equitable access in sub-Saharan Africa should have been guaranteed before people from the region were recruited for clinical trials. “Viiv’s got to be serious about making the product accessible to everyone who needs it,” Sikwese says.
Two oral versions of PrEP are already available, both as a daily pill. They have been shown to reduce HIV infection in groups at high risk, including sex workers and men who have sex with men (MSM), by up to 99%—but only when taken consistently, which many users find hard. CAB-LA promises to be more effective because adherence is much easier. The key ingredient, an antiviral compound named cabotegravir that prevents the viral genome from integrating into the DNA of host cells, is injected into the buttock and slowly released into the body. The bimonthly injections mean less hassle and more discretion for the user than a daily pill.
The trial in sub-Saharan Africa, which enrolled 3200 women, showed CAB-LA to be 89% more effective at preventing new HIV infections than oral PrEP. It also proved superior in another study, in nearly 4600 MSM and transgender women across four continents. Matthew Kavanagh, deputy executive director of the Joint United Nations Programme on HIV/AIDS (UNAIDS), calls CAB-LA “potentially the most effective biomedical prevention tool to come along in a decade.”
The World Health Organization is expected to issue safety guidelines for CAB-LA in July, which should spur countries to follow FDA’s lead and approve it. UNAIDS has had initial conversations about financing its distribution with donors, Kavanagh says, including the U.S. President’s Emergency Plan for AIDS Relief, the major funder of oral PrEP in Africa. There’s also “a handful of governments that say they would like to invest in this,” he says.
But all are waiting to find out how many vials will be available and at what cost. Viiv has priced injectable PrEP at $22,000 for a year’s supply in the United States. For the world’s poorest countries, that figure needs to come down to the current price of generic oral PrEP, less than $100 annually, Kavanagh says. “If it’s a lot more than that, we’re sunk,” he says; that would make CAB-LA an “inequality booster.”
Viiv has pledged to provide CAB-LA at nonprofit prices to the poorest countries, including all of sub-Saharan Africa. But the company will not say what that price is, and in March, it issued a vaguely worded statement suggesting a voluntary license would not help achieve the goal of affordable access. The move perplexed and enraged activists, and the statement has since been taken down. Harmony Garges, Viiv’s chief medical officer, says there was a “misunderstanding about our commitment” and that the company was only “signposting that this was going to be different, more complex” than manufacturing generic oral treatment, for which Viiv has provided a voluntary license in the past.
The new commitment to work with MPP is “a step in the right direction,” says Yvette Raphael, executive director of Advocacy for Prevention of HIV and AIDS in South Africa. But, she adds, “It should have been done the minute the studies were stopped” in 2020, given that setting up generic CAB-LA production could take up to 3 years. Activists also note that it’s unclear how many low- and middle-income countries will be allowed access to generics under a license and whether Viiv will share technology to help manufacturers ramp up production.
“I appreciate from the activist side that there’s always a level of impatience,” Garges says, but negotiations with MPP started just 6 months after CAB-LA received its first regulatory approval. “I don’t view this as any kind of delayed approach.”
Lowering the price isn’t the only hurdle to providing the drug. HIV can develop resistance to cabotegravir if it is given to a person who is already infected, and the resistance can hamper other integrase inhibitors, including dolutegravir, the backbone of current HIV treatments. That’s why FDA requires injectable PrEP recipients in the United States to first undergo a sensitive HIV test. But those cost money and can be time-consuming to conduct, says Linda-Gail Bekker, director of the Desmond Tutu HIV Centre in Cape Town, South Africa. If regulators determine such tests are needed, officials will have to consider how to make them available, Bekker says.
Advocates are keen to avoid what happened with the global rollout of oral PrEP, which began in 2015 but was quickly ensnared in “demonstration projects that were too small and too slow,” says Mitchell Warren, executive director of AVAC, an HIV prevention advocacy group. By 2020, fewer than 1 million people in developing countries were on PrEP, far short of the UNAIDS goal of 3 million.
AVAC identified several other missteps to avoid this time. Campaigns that framed oral PrEP as a prevention tool specifically for those at high risk of HIV infection made some people hesitant to ask for it for fear of stigma. Requiring people to visit busy clinics to start PrEP or pick up refills heightened those fears.
Taking that lesson to heart, Andrew Mujugira, a senior research scientist at Uganda’s Infectious Diseases Institute, hopes to recruit and train health workers from within communities of sex workers, MSM, and trans people in Uganda to deliver CAB-LA. Whenever the drug arrives, he wants to be prepared, he says: “If it can be procured, if somebody can pay for it and it can be accessible, it’s game changing.”