Can health systems keep pace with HIV prevention’s breakthrough?

The promise of lenacapavir crackled through the halls in Kigali: two injections a year, near-total protection, and overwhelming demand from those too often left out of prevention trials. For a moment, it felt like history bending toward possibility. But outside the euphoria lies the harder question — whether health systems, governments, and Big Pharma can move fast enough to turn a scientific breakthrough into protection in the real world. At IAS 2025, the 13th IAS Conference on HIV Science, in Kigali, PURPOSE researchers showcased lenacapavir, the twice-yearly injectable HIV prevention already approved by the U.S. Food and Drug Administration. It delivered near-total protection across groups such as adolescents, pregnant women, and gender-diverse populations. Trial participants overwhelmingly favoured the injections over daily pills. But experts warned the next test lies not in the data but in the ability of health systems to turn science into access. Unlike oral pre-exposure prophylaxis, or PrEP, options, which could be picked up in pharmacies or community spaces, injectables demand nurses, testing, reliable supply chains, and repeated clinic visits — conditions many health systems, and the people most at risk, struggle to meet. The PURPOSE trials showed that with resources and support, the regimen can work. But outside those environments, experts fear that stigma, cost, and weak infrastructure could limit access. “With injectables, you re-medicalize prevention,” said professor Glenda Gray, director of the Infectious Disease and Oncology Research Institute at the University of the Witwatersrand. “You need a nurse, HIV testing, diagnostics at the point of delivery, and a supply chain that never fails. That is not simple.” The re-medicalization of HIV prevention When oral PrEP first became available, it offered an escape from the clinic. Pills could be picked up in community settings, at pharmacies, or even through peer networks. As a result, HIV prevention is edging toward becoming as routine as buying paracetamol. But some experts are concerned that long-acting injectables risk reversing this trend. Gray said that, unlike oral PrEP, which was designed for community settings, injectables bring prevention back into the clinic. They require trained staff, resources, and functioning supply chains in addition to clinics where people, especially young women, sex workers, transgender people, and migrants, feel safe from stigma. The question of sustainability also looms. Gray highlights the financial and logistical demands of an injection that must be repeated every six months, possibly for decades. “From the time someone turns 14 until the time they’re 50, they’re going to need lenacapavir. Is it sustainable?” she asked. For clinicians such as Loice Ombajo in Nairobi, the concern is not only technical but systemic. Trial sites in Uganda and South Africa delivered injections smoothly, but they were highly resourced environments, staffed with motivated workers and backed by international funding. The risks are felt most keenly by key populations who already struggle in mainstream health systems. In Nigeria, Onyekachi Onumara, technical officer at the APIN Public Health Initiatives, noted that stigma drives many away from clinics. He said, when donor-funded safe spaces were closed, “many just stayed away.” Young people also weigh convenience against stigma. In Lagos, researcher Amauche Ngige found enthusiasm for the simplicity of two shots a year, but many feared being seen at an HIV clinic. “People are open to using it, but out-of-pocket payment is impossible, and the fear of judgment is real,” she said. Economists add another warning. “Efficiency fixes can only go so far,” said Brooke Nichols, associate professor of global health at Boston University. “If a product demands more from the health system instead of less, the price per patient rises beyond reach,” she told Devex, noting that the need for trained nurses, HIV tests, syringes, diagnostics, and reliable supply chains all add layers of cost. Researchers involved in the PURPOSE trial acknowledged that delivery will not be straightforward. The consensus was that the regimen is medically effective but operationally complex, and its success will depend on training, clear guidance, and health system readiness. Though results from the PURPOSE trials showed what delivery can look like under ideal conditions — the supportive environment of a trial is very different from everyday clinics. In Uganda and South Africa, young women and key populations received injections on schedule, side effects were minimal, and retention was high. Clinics ran smoothly, with dedicated staff, clear supply chains, and community support. But researchers and clinicians cautioned that trial sites are not everyday clinics. They are highly resourced spaces, with motivated teams and international support, designed to remove barriers rather than reflect them. “You are working with progressive health care workers, with counsellors from the same populations, in environments designed to be welcoming,” Gray said. “Taking that to scale requires investment — in training, in building warm and receptive spaces, and in supply chains that do not fail.” For professor Francois Venter, executive director of Ezintsha at the University of the Witwatersrand, Johannesburg, the trial lessons are both encouraging and limiting. They prove the drug can be delivered safely and effectively, but they also underline how far real-world systems have to go. But he argued that the lesson should not be paralysis but urgency. “It is not so difficult that you cannot train someone in an hour or two,” he said. “When COVID vaccines came, we figured out who could give injections and got on with it. We cannot spend years waiting for perfect systems while people get infected.” The price of prevention Beyond logistics, experts also warned that more needs to be done to ensure lenacapavir is accessible. In a New England Journal of Medicine editorial, Gray and Venter pointed to the slow rollout of cabotegravir, a bimonthly PreP injectable, as a warning. Licensing hurdles, pricing disputes, and patents have slowed access to a crawl. They warned lenacapavir could face the same fate, with restricted licences, opaque pricing and “anti-diversion” clauses — which stop medicines from being resold into wealthier markets — delaying access for millions. The economics are stark. In the United States, lenacapavir carries a list price of up to $44,000 per person per year, yet research led by Andrew Hill, from the Department of Pharmacology and Therapeutics at Liverpool University, suggests the drug could be manufactured for under $100 with sufficient generic competition. At larger scales, the cost could fall to as low as $41 per person per year. Gilead says it is taking steps to address that gap. The company has signed royalty-free licences with six generic manufacturers covering more than 120 low- and middle-income countries, and completed technology transfers to enable generic production. It has also pledged to supply these countries with lenacapavir for PrEP at no profit until generics can fully meet demand, including through a partnership with the Global Fund to Fight AIDS, Tuberculosis and Malaria and the U.S. President's Emergency Plan for AIDS Relief, or PEPFAR, to reach up to 2 million people over three years. Gray and Venter have lived through the arc of South Africa’s epidemic, from denial and devastation to lifesaving treatment and prevention tools. Both see lenacapavir as potentially transformative. Gray described it as a drug that, if made widely available, could “virtually eliminate HIV transmission.” But she pointed out that at U.S. prices, a single woman’s protection would amount to roughly a million rand a year, an impossible figure for any public health budget. What it would take IAS attendees who spoke to Devex agreed that success would depend not only on the medicine but on the systems around it. For Gray, affordability comes first. “We can only do the last mile if prices drop dramatically,” she said. That will require generic licensing and technology transfer. Infrastructure is the next hurdle. Nurses will need training, diagnostics must be available, and supply chains must hold. Ombajo warned against assuming that what works in a trial will work in a district clinic. “We must build the infrastructure, train staff, and guarantee access; otherwise, we will create excitement without equity,” she told Devex. Service design will also matter. Onyeka fears that if injectables are only available in mainstream clinics, key populations will stay away. Gray agreed that stigma-free services in districts where discrimination is strongest will be critical. Others believe Africa cannot afford to wait. Venter said governments should not wait for donors to chart the way forward; instead, they should treat lenacapavir like the COVID vaccines: train providers quickly, set ambitious targets, and get millions on PrEP. “This is where governments should grab it by the scruff of its neck and say, here is how we will do it,” he told Devex.