Does six-monthly PrEP have a future following the collapse of global HIV funding?

“Lenacapavir is a product with real transformational potential that has the power to change the history of HIV,” Carolyn Amole of the Clinton Health Access Initiative (CHAI) told last week’s 13th International AIDS Society Conference on HIV Science (IAS 2025) in Kigali, Rwanda. But for that potential to be achieved, it must be delivered at scale, and for that it needs to brought rapidly to market at an affordable price, she said.

This extraordinarily efficacious form of PrEP – only requiring injections every six months – arrives at a precarious time. The Trump administration’s radical cuts to the global health programme PEPFAR remove the institution which funded over 90% of PrEP users worldwide and which was expected to make major investments in lenacapavir.

“Science is giving us powerful tools,” commented advocate Yvette Raphael. “But we don't have powerful money.”

Prospects for global access to lenacapavir were bolstered by the release of World Health Organization (WHO) guidelines supporting lenacapavir PrEP at the conference. The week before, the Global Fund announced a deal which may allow two million people in low- and middle-income countries to access lenacapavir in advance of availability from generic suppliers. It’s now possible that lenacapavir for PrEP will become available at the same time in the global south and the global north, probably in early 2026 – a “major achievement,” said Amole.

But it seems unlikely that that will be enough to achieve the level of uptake needed to shift the trajectory of the epidemic.

From approval to availability

Looking more closely at the timeline, lenacapavir’s first approval by a drug regulator came from the US Food and Drug Administration in June this year. A decision from the European Medicines Agency is expected in August or September, which should pave the way for rapid ‘pre-qualification’ by WHO. This assessment determines whether the drug meets international standards for quality and safety. While it is a separate process from the development of WHO guidelines, both are essential prerequisites before a new drug can be adopted in many low- and middle-income countries.

For the moment, Gilead Sciences is the only company producing lenacapavir. In its deal, the Global Fund will purchase supplies of the Gilead product on behalf of countries, with a few potentially getting access in 2026. But Gilead signed licensing agreements with six generic manufacturers in October last year, and these companies are now working on their own production processes and regulatory approvals. Carolyn Amole said that she expects two of these companies to be ready to supply lenacapavir by early 2027 – but more competition may be needed to bring prices down significantly.

And lenacapavir is not the only form of long-acting PrEP that is about to enter the market. According to Mitchell Warren of advocacy organisation AVAC, generic cabotegravir (injections every two months) might arrive in 2027, alongside generic lenacapavir (injections every six months). As well as these potentially more affordable options, even longer-acting versions may come to market the same year, but they will be under patent – a four-monthly version of cabotegravir and an annual version of lenacapavir. Completing this “innovation pile-up”, a monthly PrEP pill, currently known as MK-8527, could follow in 2028.

Of course, all of these timelines are tentative and depend on multiple processes moving forward without major challenges or delays.

Whatever happened to cabotegravir?

The anaemic roll-out of injectable cabotegravir weighs heavily on advocates’ and policy makers’ minds when considering the prospects for lenacapavir. Despite its high degree of efficacy first being demonstrated in 2020, of the eight million people who had ever started PrEP by the end of 2024, just under 28,000 people were estimated to have ever used cabotegravir, and over half of them were in the United States. Cost remains a barrier, and generic versions are still not available.

PEPFAR did have ambitious plans for cabotegravir scale-up in Africa, but numbers were already well below targets when the Trump administration put a halt to all PrEP provision – apart from to pregnant and breastfeeding women – in February this year. Dr Trena Mukherjee, a former USAID technical adviser, told the conference that up to the end of September 2024, PEPFAR had supported cabotegravir initiations for 3940 people in Zambia and 3020 people in Zimbabwe, but it seems that other countries had a few hundred users at most.

African government officials reported that the sudden stop to US support has closed services that were providing PrEP, left them without the staff required and disrupted the logistical and data systems that underpinned their programmes. Taiwo Olakunle of the Nigerian Ministry of Health said that the funding freeze raised ethical concerns concerning the risk of drug resistance for people who had taken part in pilot projects.

Several thousand have also accessed cabotegravir through research studies and demonstration projects, and some of these have been able to continue, including Project PrEP in South Africa. Funded by Unitaid, this is offering adolescent girls and young women a choice of PrEP options – cabotegravir injections, the dapivirine vaginal ring and oral PrEP – in a wide range of settings.

Professor Saquia Mullick said that Project PrEP has demonstrated strong demand for long-acting options (two-thirds choose cabotegravir), but one product doesn’t suit all people all the time. Work to raise awareness and understanding of PrEP options in the community has been essential.

“Product innovation has to be matched with delivery innovation,” she said. Pharmacies, vending machines and home delivery are favoured over clinics to collect PrEP refills; young women appreciate less frequent follow-up visits and HIV self-testing; and they want regular communication between appointments, for example through Facebook or WhatsApp groups.

Facing financial realities

At last year’s AIDS 2024 conference, multiple presentations focused on ‘PrEP choice’. But while Project PrEP has survived the funding cuts, other studies with this focus have not, and some are now asking whether providing too many options risks making things unaffordable for governments and the few donors who remain committed to HIV prevention.

“I get the concept of choice, but in the current funding landscape, don’t we need one simple message to politicians?” asked Professor Niklaus Labhardt of the University of Basel. “Shouldn’t we simply say: let’s give lenacapavir to everyone who could benefit?”

Professor Linda-Gail Bekker of the University of Cape Town acknowledged the dilemma but said she had been struck by data showing significant numbers continuing to prefer oral PrEP, sometimes due to a fear of needles. “I think we need to keep choice on the table, but we’re going to have to find ways to do that in this time of austerity,” she said.

 

With PEPFAR funding for PrEP gone – and unlikely to come back – many are asking African governments to step up their commitment to HIV prevention. Professor Lloyd Mulenga of the Ministry of Health in Zambia, the African country with the largest injectable PrEP programme, stressed the importance of his officials doing the detailed technical work to make a strong investment case for HIV prevention. They need to convince the Ministry of Finance that specific PrEP programmes will lower the economic burden of HIV and have a profound impact on health.

“When it comes to budgeting, you prioritise what you think are game changers to fight public health challenges,” he said. “If you don’t do that, the politicians are not even going to listen to you.”

Dr Yogan Pillay, a former South African government official now at the Gates Foundation, agreed, adding that health policy makers also need to consider which programmes to cut. “We are very good at putting more and more things on the agenda to be funded, but we never ever think of what we’re going to stop doing,” he said.

He noted the importance of WHO’s work to define an essential package of services to focus on going forward.

Next steps under scrutiny

The new WHO guidelines recommending lenacapavir as PrEP are broad, permitting access to most people at risk of HIV, including during adolescence, pregnancy and breastfeeding. They are clear that readily available rapid HIV tests can be used by people taking all forms of PrEP, and there is no need to use RNA (viral load) tests – despite hopes that they would detect breakthrough infections more rapidly, these expensive assays have turned out to be unreliable.

The WHO guidance has been broadly welcomed, but there has been some disquiet about the details of the deal between the Global Fund and Gilead. Under this arrangement — originally intended to also include PEPFAR — the Global Fund will purchase lenacapavir from Gilead for up to two million people in 120 low- and middle-income countries. Many say that two million people using lenacapavir is nowhere near ambitious enough.

 

Also, if countries want their populations to benefit, they must cover part of the cost using their existing Global Fund allocations. These grants are already under pressure – following reductions in US contributions, most countries have seen cuts of 10% or more. As a result, programmes were already being scaled back or restructured even before countries were asked to divert resources to support lenacapavir access.

At the conference’s opening ceremony, IAS president Professor Beatriz Grinsztejn of Brazil said the agreement was, overall, excellent news. But she criticised the decision to keep the price paid by the Global Fund to Gilead confidential.

“Not to disclose the price at which the drug will be procured diminishes the negotiating power of countries outside the Global Fund, which includes middle-income countries like mine with stubbornly high incidence,” she said.

The price may officially be confidential, but some figures were discussed in the corridors of the conference centre. Asia Russell of advocacy group Health GAP told aidsmap that the Global Fund is paying around US$100 per person, per year. Of this, countries must deduct $60 from their existing Global Fund grants, with the other $40 being provided by the Children’s Investment Fund Foundation.

The costs compare to a reported $160 per person for cabotegravir supplied by ViiV, and between $25 and $40 for oral PrEP from generic manufacturers.

In these conditions, “only a small set of countries – I think nine countries – can begin introduction, and only for a subset of their at-risk populations,” said Carolyn Amole of CHAI. “It may remain a relatively niche product, particularly given the intensely fiscally constrained environment that we are in right now.”

Her hopes focused on the stage that comes afterwards – the introduction of generic lenacapavir, ideally produced by multiple manufacturers. She emphasised the need for a carefully managed market-shaping strategy – one that influences both supply and demand.

“Working only in one area without the other will fail every time,” she said. “You cannot negotiate a pricing deal without knowing whether the volumes will be there, and it is risky to drive demand for a product without knowing if you will in fact have a product.”

If that process is followed through, she believes it could make possible the introduction of generic lenacapavir as early as the first quarter of 2027 — “at a price competitive with oral PrEP.”