Cruel Ironies

Scientific advances collide with major infrastructure upheaval

November 12, 2025

We’re seeing one of the most challenging moments in HIV prevention history – and the cruelest ironies. On one side, science and advocacy are delivering unprecedented progress. South Africa and Zambia have approved injectable lenacapavir (LEN) for PrEP just months after US and EU regulatory approvals, with rapid WHO guidelines and prequalification paving the way for rapid rollouts in 2026 and beyond.

On the other, the global systems meant to deliver LEN and other potential innovations, like monthly oral MK-8527 are being dismantled. The US’s new ’America First’ Global Health Strategy replaces multilateralism and broad stakeholder engagement with bilateral government-to-government deals, redirecting and conditioning funds, and sidelining communities, which threatens to unravel decades of progress in HIV prevention, science and equity made possible through meaningful community engagement and leadership. And a new framework is in development to advance this strategy.

LEN Regulatory Milestones and What’s Next

In Africa, the South African Health Products Regulatory Authority (SAHPRA) led the way with a precedent-setting fast-track approval of LEN in October, followed by Zambia last week, with regulatory reviews underway in Botswana, Kenya, Malawi, Namibia, Rwanda, Uganda, and Zimbabwe. (For a full regulatory update, see here) These early wins reflect lessons learned from previous PrEP rollouts and signal growing capacity and urgency to act – the comparative graphic below shows that our global community does learn lessons, can move with speed, scale and equity, and might actually seize a PrEP opportunity instead of squandering it.

Yet as AVAC’s Moving a Product to the Real World graphic shows, approval is only one piece in the complex process. Turning regulatory milestones into public health impact depends on aligned global funders, transparent pricing and volume commitments, and community-engaged introduction strategies. Without this, innovation risks stagnation.

Global Health Infrastructure Undermined

At the same time, the US government is pushing through a new global health framework under its “America First” strategy. This week, US embassies around the world began sharing draft Memoranda of Understanding (MoUs)with partner countries, aimed at reshaping how US health aid, including PEPFAR, is negotiated and delivered. These bilateral MoUs:

  • Omit HIV prevention metrics, including PrEP and products like LEN.
  • Sideline civil society and key populations by removing requirements for community engagement.
  • Bypass multilateral coordination, ignoring WHO and regional public health institutions.
  • Favor US commercial interests, raising concerns about procurement policies and equity.

A new Think Global Health article by KFF’s Jen Kates and colleagues explores this strategy’s assumptions including a pivot from multilateralism to bilateralism, a narrow focus on commodities and frontline workers, pooled procurement, and time-limited support with the aim to “graduate” countries from assistance. Meanwhile, Devex offers perspectives from several leaders in the field who weigh opportunities, contradictions, and raise red flags about sidelined NGOs and the communities they serve, reduced ambition in US global health programming, and weakened multilateral partnerships.

These agreements could endanger the rollout of LEN and other innovations, threaten the entire prevention pipeline and violate core principles of transparency, inclusion, and global solidarity. As Jirair Ratevosian wrote this week:

“What matters now are the decisions made in budget rooms, procurement units, regulatory authorities, and community forums…. The next phase of global health will not be defined by what Washington announces, but by what countries build.”

It will be up to countries to put forth strong plans and policies on scaling up LEN and other biomedical prevention during ongoing MOU negotiations with the US government.

Resources to Navigate the Cruel Irony