HIV: Breakthrough study raises hopes of effective prevention if drug’s cost can be lowered
BMJ 2024; 386 doi: https://doi.org/10.1136/bmj.q1776 (Published 09 August 2024) Cite this as: BMJ 2024;386:q1776
Landmark results in an African trial of HIV prevention through twice yearly injection could finally break the cycle of mass infection in sub-Saharan Africa, leaders of the United Nations’ HIV/AIDS programme (UNAIDS) have said. But they warned that this could occur only if the prices currently foreseen for such treatments in the west are lowered by hundreds of times.
“The cost of the new long-acting injectable pre-exposure prophylaxis (PrEP) options, and the speed with which they are made available to the people who would benefit the most, will be decisive,” said this year’s report from UNAIDS.1
The potential of one such injectable antiretroviral, lenacapavir, has been highlighted by the results of its first trial as a preventive treatment, among adolescent girls and young women in South Africa and Uganda.2 Participants were randomly assigned to receive either lenacapavir by injection every six months or one of two common oral antiretroviral preventive treatments: F/TAF or F/TDF, commercially known as Descovy and its predecessor, Truvada. All three drugs are made by Gilead Sciences.
The results, published in the New England Journal of Medicine,2 showed that among 5338 participants 55 new HIV infections were observed, all occurring in the two oral treatment groups. A standout finding was zero new infections in the injected participants (0 per 100 person years (95% confidence interval 0.00 to 0.19)), which compared with 39 infections among 2136 participants in the F/TAF group (2.02 per 100 person years (1.44 to 2.76)) and 16 infections among 1068 participants in the F/TDF group (1.69 per 100 person years (0.96 to 2.74)). Background HIV incidence in 8094 screened participants was 2.41 per 100 person years (1.82 to 3.19).
“Even now, when I look at that graph, I get shivers,” said the lead researcher, Linda-Gail Bekker, from Zimbabwe, at last month’s AIDS 2024 conference in Munich as she described the results to a standing ovation. The relative underperformance of the oral PrEP regimens was less a sign of inefficacy—both have proved effective in the west—than of poor compliance, she said, exacerbated by a lack of access to pharmacies and the stigma that such medicines carry in some African countries.
“If you take a six monthly injection you only have to make this decision twice a year,” Bekker told the Munich conference. “You could quietly slip in [to the doctor or pharmacy], under the guise of getting your contraceptive; nobody even needs to know.”
But the optimism was tempered by concerns about price and access. In the United States, where lenacapavir has been approved for treatment but not prevention under the brand name Sunlenca, its official price for the first two injections is $42 000 (£32 900; €38 500).
Progress in Africa
Sub-Saharan Africa is increasingly seen as a success story and model in the fight against AIDS. Worldwide, 1.3 million new infections were seen last year, down 39% since 2010. But in Sub-Saharan Africa new infections last year were down 56% from 2010.
The global number of new infections is still three times the interim target, agreed at the UN, of no more than 370 000 new infections by 2025. UNAIDS has acknowledged that this target will be missed. Only four countries—Kenya, Malawi, Nepal, and Zimbabwe—are deemed “well on track” to reach the ultimate target of reducing new HIV infections by 90% by 2030.
The gains of recent years have been driven by a steady decline in sub-Saharan infection rates. The main factor behind this, says UNAIDS, has not been education or social programmes, nor preventive treatment in uninfected people, but widespread access to PrEP among those who are already infected, which reduces their risk of passing the virus on.
Many of the countries where AIDS is spreading unchecked are in the middle income category: too wealthy to obtain steep discounts but not rich enough for people to afford their own drugs. Last year was the first in which most new infections occurred outside sub-Saharan Africa. The fastest growth is in eastern Europe, where the AIDS 2024 conference heard that Russian propaganda was undermining opioid addiction programmes and other preventive measures.
But while the picture is improving in sub-Saharan Africa, the region remains the largest reservoir of the disease. It is also the only part of the world where infections in men are falling more quickly than in women. Women and girls now make up 62% of the people recently infected there.
Gilead to the rescue?
A spokesman for the manufacturer, Gilead, told The BMJ that “it is currently too early to state the price of lenacapavir for PrEP, as we await additional phase 3 clinical trial data”—namely, a second trial in men, due later this year or in early 2025. Gilead has promised “to deliver lenacapavir swiftly, sustainably and in sufficient volumes, if approved, to high-incidence, resource-limited countries, which are primarily low- and lower-middle-income countries.”3
The reduction would need to be almost 1000-fold from the current US price for Sunlenca. Another injectable preventive drug, cabotegravir—made by Viiv, a company largely owned by GSK—is already available in Africa for about $180 a year, but even this price has severely limited its use. South Africa, officially an upper middle income country, has a budget for PrEP of about $40 per person per year.
Despite its relatively high income South Africa is unlikely to be left out of Gilead’s plan, since the lenacapavir study was conducted there, and the Declaration of Helsinki, the main ethics statement of the World Medical Association, forbids conducting research among people who will not benefit from any resulting treatment. The fact that Gilead chose to prove lenacapavir’s benefits in an African setting has been widely seen as evidence of the company’s good intentions.
Research presented at Munich found that a $40 yearly price for lenacapavir was attainable, but only at much higher manufacturing volumes than Gilead is likely to rapidly achieve: more than 10 million person years each year. This would require rapid sharing of rights with generic manufacturers supplying developing countries, as Gilead has already agreed to do.
However, Gilead still resists sharing its rights with the WHO supported Medicines Patent Pool, which would itself distribute rights to generic makers. In May this year an open letter from 300 politicians, activists, scientists, and celebrities urged the company to reverse that policy, calling such a decision a “game changer.”4
Winnie Byanyima, head of UNAIDS, has added her voice to that chorus. Lenacapavir is “so highly effective, it’s in a different category of preventive medicines,” she told Agence France-Presse. “We could come close to ending this disease.”
She said, “Gilead has an opportunity to save the world. To save the world, literally [from the HIV pandemic]. They can be the company that wins a Nobel prize, for example. Reward doesn’t come just through money; there is also recognition . . . imagine how great it would be.”