PrEp – pre-exposure prophylaxis – is the most promising HIV prevention yet in the history of the Aids epidemic, writes Stephanie Nolan of The New York Times. Yet in Africa, while many young women start PrEP, few stay on it.
Nolan writes:
Young South African women are among the most vulnerable in the world to HIV, but they say the daily pills, known as PrEP, bring their own challenges. The women may spend an unexpected night away from home and miss a dose, or forget for a day or two. Or their families snoop through their drawers, find the pills and know their business. Or their boyfriends see them taking the drug and get suspicious: Is that for prevention, or do you have HIV?
The persistent stigma surrounding HIV and the visibility of the drugs are big deterrents, said Dr Linda-Gail Bekker, director of the Desmond Tutu HIV Centre at the University of Cape Town.
So when a volunteer with the Treatment Action Campaign heard some years ago that a clinical trial in South Africa was testing PrEP as a shot delivered once every couple of months, she thought: This is the solution we need: private and invisible, and a woman needs to remember it only six times a year.
The trial found the injectable PrEP hugely successful, nearly eliminating women’s risk of contracting HIV and 88% more effective than the daily pill. But there’s still no sign of those injections in Soweto.
The drug is called long-acting cabotegravir, or Cab-LA, made by British pharmaceutical company ViiV Healthcare. ViiV is majority owned by the pharmaceutical giant GSK, with Pfizer and Japanese drug company Shionogi as shareholders.
The only country where regulators have approved Cab-LA is the United States; the Food and Drug Administration authorised the injectable drug’s use in December. Cab-LA is priced at $22 200 per patient per year there.
After the clinical trial results were announced in 2020, Viiv said it would apply immediately to have the drug approved by regulators in all African countries where it was tested.
Dr Kimberly Smith, ViiV’s head of research and development, said ViiV would aim for a “not-for-profit, not-for-loss price”.
The usual path to broaden access would be for the company to license generics makers to produce a cheaper version for markets like South Africa. But in March, Viiv announced that for the foreseeable future, it would not grant licenses for generic makers, and could find no partner capable of making the drug.
ViiV would not tell The New York Times the price it was proposing in developing countries, but apparently the company told those working on the rollout that it expected it to cost $250 per person annually. Although that is far lower than in the US, it is not low enough for a country like South Africa, which needs to administer hundreds of thousands of doses, where oral PrEP costs about $50 per person per year.
Drug access activists responded angrily to $250 a year being “accessible pricing” and demanded ViiV commit to voluntary licensing of the drug.
Then ViiV announced an agreement with the Medicines Patent Pool, a United Nations-backed nonprofit that works to make medical treatment and technologies accessible. The deal permits up to three generics companies to make the drug for sale in 90 low- and middle-income countries. It will take at least three years for a generic to be available for regulatory approval. ViiV has also submitted an application to the World Health Organization for prequalification of the drug, to expedite those approvals.
Drug access activists called the limited voluntary license progress unsatisfactory. Leena Menghaney, who leads the South Asia access campaign of Doctors Without Borders, said it was “limited and disappointing”.
The deal leaves out all countries where ViiV holds a patent on Cab-LA — including Brazil, where gay men and trans women volunteered for the trials in which the drug was tested.
“ViiV has not learned the lessons of the past 40 years because their pricing obstructs rather than conveys access,” said Asia Russell, executive director of the group Health GAP, which campaigns for drug access. “This is a pandemic-altering intervention, and any day lost is measured in preventable infections.”
Researchers and activists believe the company is worried about how much it may earn on Cab-LA because other HIV prevention drugs are in trials as injectable PrEP, too. Some have longer dosing cycles — that is, they could be injected only two or three times a year, which would probably appeal to more women, and could be synced with contraception shots. Researchers also believe ViiV might be concerned about what it would earn in the US, a company’s most lucrative market. Cab-LA costs roughly the same as the brand-name oral PrEP drug Truvada in the US, but a far cheaper generic oral PrEP is available.
A cost-of-goods study by the Clinton Health Access Initiative compared Cab-LA with similar products and concluded that Cab-LA could profitably be produced for $16 per patient per year — one-third the cost of oral PrEP in SA — assuming a volume of 800 000 patients. That price is estimated for production by a generic maker, probably in India, not at ViiV’s plant in Britain. The analysis noted that the amount of active pharmaceutical ingredient, a key cost in drug production, for six injections per year would be cheaper than that in 365 pills.
Smith of Viiv said that the study seriously underestimated the cost. “The complexity of cabotegravir manufacturing is significant,” she said.
At a recent Aids conference, major global health agencies announced a new collaboration with charitable agencies and advocacy groups to try to broaden access to the injectable drug. They will work first on getting ViiV’s product into low-income markets, possibly by negotiating with the company over guarantees for purchase volumes that may entice it to agree to lower prices.
In the longer term, the partners will provide funding to help makers of generic versions escalate manufacturing. The partners include the Children’s Investment Fund Foundation, which pledged $33m to the effort this month, and the Bill & Melinda Gates Foundation.
But generics makers would be watching the other drugs in the pipeline and act accordingly. Another obstacle is that injectable PrEP programmes will need funding for more than just the drug’s cost. The shots would need to be administered by healthcare workers, requiring syringes and other medical supplies. African governments considering rolling out injectable PrEP would need financial support from multilateral agencies like the Global Fund to Fight Aids, Tuberculosis and Malaria, so as not to take funds from other HIV education and prevention initiatives.
While there is excitement across sub-Saharan Africa about the idea of injectable PrEP, there is also a need to prove that women will want and use it.
“We hear from many young people this would be ideal, but the proof is in the pudding,” Bekker said. “It’s not certain healthy women will attend a clinic every two months for the shot, and the key would be making it available in community clinics, framing it as part of a healthy sex life rather than as a medication associated with risk.”
Smith said ViiV hoped to learn from the history of long-acting injectable contraception like Depo-Provera, which is delivered in a shot four times annually and which many women in the developing world choose as their preferred method of birth control. But there is no guarantee bimonthly PrEP shots will gain favour because HIV has a unique stigma.
ViiV has committed to supplying the drugs for only an initial implementation study in South Africa, and no donor has yet committed to funding others. “The most important thing is to get this out there, into clinics and into people’s hands,” Bekker said.
See more from MedicalBrief archives:
Long-acting ARV given as two monthly injectable PrEP protects against HIV
Services must be strengthened to encourage PrEP users
Preventive drug regimen in at-risk group increases PrEP uptake — Eswatini
US study finds PrEP regimen works