After a lifetime on the frontiers of the fight against HIV, Linda-Gail Bekker could finally see the end of the epidemic in sight. For decades, HIV experts had dreamed of an elusive vaccine to block the ongoing chain of infections, which still sees more than 1 million people worldwide contract the virus annually. Bekker, a 62-year-old medical professor from the University of Cape Town, had helped identify a drug that could do just that.
But now, thanks to the Trump administration’s executive orders, it’s unclear when—or possibly even ever—this breakthrough medicine will see the light of day.
At the AIDS 2024 conference held in Munich last July, Bekker had triumphantly unveiled the results of a momentous clinical trial she had led, called PURPOSE 1. It showed that lenacapavir, an antiretroviral developed by the pharmaceutical company Gilead Sciences, could prevent sexual transmission of HIV with 100 percent efficacy by disrupting the function of the virus’s capsid protein, which allows it to replicate.
Even more remarkably, compared with existing daily pre-exposure prophylaxis (PrEP) pills, which do a similar job, injections are only required every six months. While not strictly a vaccine, lenacapavir promises to be the next best thing. It was named as 2024’s “Breakthrough of the Year” by the prestigious journal Science, and Gilead promptly committed to manufacturing 10 million doses by 2026, enough to treat 2.5 million people, ahead of anticipated regulatory approval later this year.
A collaborative effort between the medicines-financing initiative The Global Fund and PEPFAR, the US government’s global HIV/AIDS program, had pledged to procure 2 million of those doses over the course of three years, which would be directed toward countries with the highest incidence of HIV, most notably in sub-Saharan Africa. But with President Donald Trump’s decision to freeze all foreign aid funding, this plan has been left in tatters.
“There’s despondency and a sense of tragedy,” says Bekker. “Because just as we’ve had the breakthrough, we also see the taps turning off of resources. We had a laid-out map where the product would be supplied via PEPFAR and The Global Fund while we wait for generics [cheaper off-label versions of lenacapavir] to come online, which will take 18 months to two years. And at this moment, that plan is falling through in front of our eyes.”
While a temporary 90-day waiver has been issued for PEPFAR funding, this has only reinstated funding for life-saving antiretroviral treatments for HIV-positive individuals. Existing forms of PrEP are covered, but only for pregnant or breastfeeding women. There have been no indications that the planned purchase of lenacapavir will be fulfilled.
According to Kenneth Ngure, an HIV-prevention expert in Kenya and president-elect of the International AIDS Society, the loss of PEPFAR funding for prevention represents a major setback in the world’s ability to control HIV. “Even if The Global Fund partners with others, they will probably not be able to reach the number of doses they had promised,” he says. “We have this potential game-changer, which could accelerate the end of HIV as a public health threat, and yet it looks like access will be highly compromised.”
For Ngure and others, there is a sense of history repeating itself. The major limitation of PrEP is that adherence is notoriously poor, with studies showing that target groups often struggle to access or forget to take daily pills and feel stigmatized doing so. “We know that particularly for young people, taking a daily oral PrEP pill is challenging,” says Bekker. “We’ve tried all sorts of things, like sending text messages. São Paulo is even giving PrEP in a dispensing machine. But it’s sometimes very difficult to take something daily when you’re not sick and you’re doing it for prevention.”
Longer-acting injectables have long been viewed as a better way forward, and in 2021, the HIV field was galvanized by promising trial results for cabotegravir, a form of injectable PrEP that only needed to be administered every two months, with a trial demonstrating that people receiving this drug had 90 percent less risk of contracting HIV compared with oral pills. Yet access has been the major hurdle.
Last month a new study revealed that while regulators in 53 countries have approved cabotegravir, rollout has been painfully slow. Generic versions of the jab are not expected to become available until 2027. In Africa and Asia, where cabotegravir is most needed, the only access so far has been through so-called Phase 4 or implementation science studies, which attempt to understand more about the real-world challenges of offering a new drug by dispensing it to a few thousand people.
And also as a consequence of orders coming out of the White House, a number of these Phase 4 studies have abruptly ceased. “They’re very concentrated in East and Southern Central Africa,” says Bekker. “Some of them were PEPFAR supported, and with the stop-work order, these studies have ground to a halt.”
The frustration for researchers like Bekker is that while long-acting injectables are extremely effective at blocking HIV transmission, to end the epidemic, their rollout needs to be as rapid and as wide-reaching as possible. She points out that to prevent over a million new infections each year, these jabs need to be targeted at HIV hotspots and administered on a scale of millions—exactly as the plan with lenacapavir was proposing.
“We’ve seen with both cabotegravir and oral PrEP that if you get a new tool, but roll it out gently, that will not impact the epidemic,” says Ngure. “The number of new infections still outpaces the impact of the tool. You need something which is potent and to roll it out fast.”
With lenacapavir, things were supposed to be different. Gilead has partnered with six generic drugmakers, which have been licensed to produce enough of an off-label supply of lenacapavir to cover 120 countries. Estimates have suggested that if the global demand exceeded more than 20 million doses, the manufacturing costs could fall to just $35-40 per person per year. However, Bekker says that PEPFAR was expected to be a significant buyer, and without its financial clout the commercial viability of manufacturing generic lenacapavir at vast scales is in doubt.
“It requires a nice healthy demand to ensure that for each of the generic companies, it’s going to be worth their while,” says Bekker. “We are all hoping that governments [across sub-Saharan Africa] are writing the generic product into their budgets for the future, but the reality is that in the interim, we were relying on donor funding. Even my country, South Africa, which has a good GDP and funds 80 percent of its HIV response, is already purchasing antiretrovirals for 6 million individuals annually. I would imagine it will take them some years to be able to mobilize the money for lenacapavir as well.”
With PEPFAR seemingly now focused primarily on the treatment of existing patients, at the expense of prevention, clinicians like Nomathemba Chandiwana, a physician-scientist at the Desmond Tutu Health Foundation in South Africa, are concerned that the infection rate will begin to rise rather than fall, something which will have a marked public health impact across the African continent and beyond.
Speaking at last week’s NCD Alliance Forum in Kigali, Chandiwana explained that the consequences of new infections are not solely related to HIV itself. Research is increasingly showing that people living with long-term HIV infections, even those controlled by antiretroviral treatment, are at a greater risk of developing metabolic conditions such as hypertension, obesity and type 2 diabetes, a disease burden which is already on the rise in sub-Saharan Africa. “HIV itself disrupts your metabolism, as do many of the antiretrovirals,” says Chandiwana. “We see the same chronic diseases in people living with HIV as we do in the general population, but at an earlier age and in an accelerated fashion.”
Because of this, there is also a need for a new generation of HIV treatments, and one concept being explored was to use lenacapavir as a foundation of future combination therapies for those already with the virus. As well as potentially alleviating some of the metabolic side effects, it was hoped that this could lead to treatment protocols that did not require HIV-infected individuals to take daily medication.
“Various ideas have been mooted,” says Bekker. “Could you combine bimonthly cabotegravir with a six-monthly lenacapavir injection [as a form of viral suppression], so you’d only come in six times a year for treatment, and it would all be injectable? There’s a weekly antiretroviral pill in the works, and could you combine that with a six-monthly injectable? This could be very liberating for people, as they tell us all the time how stigmatizing it is to need to take daily medication.”
Yet many of these studies are now in doubt, as Bekker says they were expected to be funded by US resources. “It’s not just PEPFAR; we’re also worried about restrictions being placed on other sorts of research funding, such as the National Institutes of Health,” she says. “It’s just going to get harder to innovate and move progress forward.”
According to Ngure, there is still hope that other donors may emerge who can support The Global Fund in procuring lenacapavir, while Bekker says she is exploring new options for funding HIV prevention and research through European agencies, and possibly donor funding from sources in Scandinavia, Japan, and Australia. At the same time, she believes that the events of the past month have illustrated that African countries need to become capable of funding more preventative efforts themselves.
“Somehow Africa needs to step up and contribute to the fight,” she says. “I think that’s the big question. How much we can also contribute on this continent through countries which haven’t necessarily been able to cover a big amount of research and development but in the future need to.”
At the same time, she is afraid that without the same resources coming from the US, the unique opportunity provided by lenacapavir could be lost.
“It’s incredible that this has happened just as we’ve had the breakthrough,” she says. “I think this is going to set us back many years and ultimately cost a lot more in public health spending. Because ultimately, if we can bring this epidemic under control more quickly, it’s going to save the planet more money in the long run, and save lives too.”
