Introduction

Lenacapavir has been hailed as a breakthrough in HIV prevention, and for good reason. A twice-yearly injectable form of PrEP could be transformative in settings where stigma, health-system friction and the burden of taking a daily pill continue to undermine prevention uptake. South Africa, which carries the world’s largest HIV epidemic, has moved quickly to introduce it and is now seeking a voluntary licence to manufacture it locally. That effort has support from Unitaid and other partners, and it comes at a moment when global enthusiasm around Lenacapavir is high.

But the real question is no longer whether Lenacapavir is scientifically important. It is whether enough of it can be made available, quickly enough and on terms that make sense for a country like South Africa. That is not only a political question. It is an intensely practical one. South Africa has around 7.7 to 8 million people living with HIV, adult prevalence remains extraordinarily high, and domestic resources already finance roughly 74% of the national HIV response. In other words, this is not a country waiting passively for charity. It is a country with a massive, generalized epidemic, significant domestic commitment, and an obvious need for far greater supply than the initial rollout can offer.

A prevention breakthrough collides with the arithmetic of a generalized epidemic

The central problem is scale. Lenacapavir may be revolutionary, but South Africa’s epidemic is too large for symbolic access to make a decisive difference. The first phase of rollout is expected to support about 456,000 initiations over two years, funded by a Global Fund grant of $29.2 million plus an additional $5 million from NACOSA. That is meaningful as a launch strategy. It is not enough as an epidemic strategy in a country of more than 60 million people, with a very large population still HIV-negative but at substantial risk of infection.

That is why the debate should not be framed only as one of sovereignty or symbolism. It is also about basic feasibility. For a country hoping to bend the curve of a generalized epidemic, a few hundred thousand doses are a beginning, not a solution. The practical concern raised by South African officials and advocates is therefore well founded: if the country is serious about ending AIDS as a public health threat, it needs a far larger, more reliable and more affordable supply base than the current arrangements provide.

This also explains why the licensing question has become so contentious. In 2024, Gilead granted six voluntary licences to manufacturers in India, Egypt and Pakistan to supply 120 low- and middle-income countries. No South African manufacturer was included, despite South Africa’s major role in the epidemic, its research contribution, and its existing pharmaceutical base. Reuters reported that Gilead later indicated it was open to an additional licence for a South African producer, subject to assessment of manufacturing standards. That matters, because the issue is not only fairness. It is whether supply can be expanded in a way proportionate to need.

This is political - but it is also about capability, memory and leverage

There is of course a political dimension, and it resonates strongly in South Africa. The argument over Lenacapavir recalls the country’s earlier battle over access to antiretroviral medicines, when 39 pharmaceutical companies challenged the South African government over the 1997 Medicines Act in a case that became a defining moment in the global access-to-medicines movement. That history matters because it reminds us that South Africa has long had to fight not only the virus, but also the rules governing who may produce and distribute life-saving tools.

But the present dispute is not a simple replay of that earlier struggle. South Africa today is not merely demanding lower prices for imported products. It already manufactures antiretrovirals and pays for most of its HIV response from domestic resources. The stronger argument, then, is not just that Africa should not remain dependent on others in principle. It is that South Africa has both the epidemic burden and the institutional basis to justify a more central role in production. Putting such a country at the mercy of limited external allocations makes little strategic sense for South Africa or for the wider African response.

The controversy over Egypt illustrates the point. Civil society criticism has focused not simply on the fact that Egypt received a voluntary licence while South Africa did not, but on the mismatch between licensing geography and epidemiological need. A licensing regime that does not reflect where the burden lies will struggle to command legitimacy, especially when the country left out is both heavily affected and industrially more relevant to regional scale-up. That said, one nuance is important: South African manufacturers still need to demonstrate that they meet the technical and quality requirements necessary for production. The political case for local manufacture is strong, but it still must be matched by proven manufacturing readiness.

The Global Fund can shape the market, but it cannot substitute for industrial strategy

The margin comment on the Global Fund is exactly right to push this point further. It would be too simple to say that the Global Fund is merely a buffer. The Fund has a substantial history of market shaping, and it is explicitly presenting Lenacapavir as part of that agenda. It has said it “actively shapes markets” and has signed a landmark access agreement with Gilead to introduce Lenacapavir in low- and middle-income countries alongside high-income markets. Its 2025 Results Report likewise presents the agreement as a major access breakthrough.

So the fairer argument is this: the Global Fund can help accelerate market entry, pool demand, lower prices, de-risk procurement and expand initial supply. It can also help send an important signal to manufacturers that there will be a viable market at scale. The agreement with Gilead is meant to supply enough Lenacapavir for up to 2 million people over three years, which is a significant intervention in global market terms.

But market shaping has limits. It is most effective when there are multiple producers, expanding manufacturing capacity and a pathway from donor-supported introduction to durable, large-volume supply. In the case of Lenacapavir, the problem is that supply still originates from a tightly controlled licensing architecture, with too few producers and volumes that remain small relative to need in high-burden settings. The Global Fund can shape that market; it cannot by itself create full manufacturing pluralism or override the strategic choices of the patent holder. That is why South Africa’s push for local production matters so much. It is not an alternative to market shaping. It is what market shaping needs to become structurally meaningful.

Conclusion

The Lenacapavir story in South Africa should therefore be read less as a purely political drama and more as a test of whether the global HIV response can align innovation with epidemiological reality. South Africa’s frustration is not abstract. It stems from the mismatch between the size of its epidemic, the scale of its domestic investment, its existing manufacturing base, and the relatively limited supply currently on offer.

That is the real access test. If Lenacapavir remains scarce, centrally controlled and dependent on narrow licensing decisions, it will remain a breakthrough for some rather than a turning point for the epidemic. If, however, South Africa can secure reliable supply, build or prove manufacturing readiness, and integrate the product into a response it already largely finances itself, then Lenacapavir could become something more important: not just a scientific advance, but a practical tool deployed at the scale a generalized epidemic demand.

Christian Djoko Kamgain, PhD, Editor-in-Chief of GFO/OFM