The Scientific Journey of Lenacapavir — and the Urgency to Defend HIV Prevention Science 

On June 11, AVAC hosted a conversation, The Scientific Journey of Lenacapavir: From basic science to clinical development to impact, to explore how US support from NIH for basic science and South Africa’s clinical research infrastructure made possible the development of lenacapavir for PrEP (LEN), a discovery in HIV prevention that went on to be named Science magazine’s 2024 Breakthrough of the Year.

As the field anticipates initial regulatory approval from the US FDA by June 19 and a WHO recommendation in July, Linda-Gail Bekker of the Desmond Tutu Health Foundation, Wes Sundquist of the University of Utah and Mitchell Warren of AVAC underscored how this moment of promise is threatened by sweeping attacks on science, research and the very systems that made the development of LEN possible.

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Getting PrEP Rollout Right This Time

Lessons from the Field

Thirteen years after oral PrEP’s introduction, global uptake remains slow, with just over 9 million initiations—falling short of UNAIDS’ 2025 targets. While HIV infections are declining in some regions, others are experiencing increasing epidemics. Despite challenges, lessons from oral PrEP and CAB rollout have strengthened health systems for scaling up longer-acting PrEP.

AVAC undertook a qualitative landscaping analysis to identify actionable lessons and recommendations across seven countries—Brazil, Kenya, Nigeria, South Africa, Vietnam, Zambia, and Zimbabwe—exploring themes of:

  • Successes and challenges with daily oral PrEP introduction and scale-up and what can be done differently for new PrEP products.
  • Public health system readiness for the introduction and scale-up of new PrEP products.
  • Considerations for improving and accelerating PrEP regulatory approval, normative guidance, demand generation, stakeholder engagement, and health systems strengthening.

This analysis, conducted across seven countries before the January 2025 US foreign aid freeze, identifies urgent actions to sustain momentum. US foreign aid cuts are severely impairing PrEP delivery, jeopardizing remarkable progress made in the last 20 years. In the wake of this disruption, it is vital that efforts to mobilize and sustain an effective HIV response learn from the past and reach UNAIDS’ targets for 2030 by incorporating these insights into future planning.

Visit PrEPWatch for the full report and individual country profiles.

Avac Event

1st International Workshop on Long Acting Anti-Infectives (LAAI) 2025

The International Workshop On Long Acting Anti-Infectives (LAAI) is a crucial platform for advancing the development, implementation, and scale-up of long-acting and extended-release (LA/ER) anti-infective therapies. 

AVAC’s Stacey Hannah will present on, Getting It Right This Time: The Impact of PEPFAR Stop Work Orders on Injectable PrEP and Implications for LEN Rollout.

Why HIV Prevention Must Not Be Left Behind

In this presentation at the INTEREST 2025 conference, Rhoda Msiska of Copper Rose Zambia emphasizes the urgency of protecting the progress made in scaling up PrEP and the need to act now to expand access to new HIV prevention tools like injectable lenacapavir (LEN) and the Dual Prevention Pill (DPP).

Modelling Shows the Potential of LA-PrEP

Modelling data from South Africa demonstrate the potential of injectable PrEP to dramatically reduce HIV incidence by up to 90% by 2044, and potentially even sooner with more aggressive uptake. This potential goes beyond South Africa, lighting the way toward epidemic control the world over. Excerpted from PxWire.

PrEP Delivery Imperiled

Programs for delivering PrEP have been shuttered all over the world by the withdrawal of the US government from global health. This graphic illustrates some of the severe measurable impacts of these cuts. Excerpted from PxWire.

PxWire Volume 15, Issue 2

The field of HIV prevention is confronted with two opposing forces; programs for delivering PrEP have been shuttered all over the world by the withdrawal of the US government from global health. At this same moment in history, next-generation long-acting products hold great promise to accelerate HIV prevention and help the world achieve epidemic control. Navigating these seismic developments requires unprecedented coordination, solidarity, and courage.

Global health champions can defy the hatred, fear, and greed that are dominating politics in so many places around the world. Together we can innovate, create, and protect the advance of HIV prevention and global health. This issue provides a snapshot on threats to delivering PrEP, the potential of injectable lenacapavir (LEN) for PrEP, and on the implications of upstream research and development of other long-acting PrEP.

Read below or download the PDF version.

Progress in PrEP Uptake: Threatened

  • PEPFAR documented 2.5 million new PrEP users in 2024, who could now lose access to PEPFAR- supported PrEP services. US Department of State issued a limited and inconsistently implemented waiver in February, allowing for continued provision of HIV treatment but restricting PrEP access to pregnant and lactating people only.
  • These actions will result in 3.5 million who identify as key populations (KPs) losing access to all HIV prevention programming under PEPFAR, according to 2024 PEPFAR data tracking KP use of PrEP. These groups have higher rates of HIV incidence and face additional barriers to accessing services now that targeted programs are suspended.
  • PEPFAR had a goal of 100,000 people initiating cabotegravir (CAB) for PrEP in 2025. But only 5,000 individuals had initiated by October 2024. The suspension of PEPFAR funding imperils scale-up of this long-acting product.
  • These figures represent just some of the disruptions that are decimating PrEP delivery. Learn more here: Impact of PEPFAR Stop Work Orders on PrEP
  • Overcoming this challenge, restoring, sustaining, and accelerating PrEP access is imperative and possible if the field works together.

For the last eight years, AVAC has proudly worked with PEPFAR to document PrEP uptake and its impact around the world. That stopped in January with a stop work order from the US government. But protecting access to PrEP is vital. Are you leading a PrEP program? Whether supported by PEPFAR or not, we invite you to work with us to ensure global data on PrEP is not lost. Find us at [email protected].

PrEParing for New Products

  • Approval by the US Food and Drug Administration (FDA) for injectable 6-month LEN for PrEP is expected in June, with WHO guidelines expected in July. See the full timeline.
  • Modelling data from South Africa demonstrate the potential of injectable PrEP to dramatically reduce HIV incidence by up to 90% by 2044, and potentially even sooner with more aggressive uptake. This potential goes beyond South Africa, lighting the way toward epidemic control the world over.
  • The field must be prepared for swift action once LEN is approved and recommended, to ensure this opportunity is not squandered. As AVAC’s interactive timeline, Tracking LEN Rollout, outlines, donors, ministries of health, manufacturers, regulators, and civil society all have a role to play to pave the way for swift, equitable and effective introduction of LEN for PrEP.

The Latest R&D in the Prevention Pipeline

  • The HIV prevention market is headed toward a period of significant opportunity—and possible congestion—as a slate of new products are on track for continued development and potential introduction to the market in 2027 and 2028.
  • Generics for 2-month CAB and 6-month LEN, along with ViiV’s 4-month CAB, Gilead’s 12-month LEN, and Merck’s monthly oral MK-8527 PrEP pill (if further development and approvals are successful) could all enter the market by 2028.
  • The possibility of so many products on the market, including four different formulations of injectable PrEP, means that it is imperative the field prepares for this future now.
  • Markets and policies must be built to support the products in the market already, so that new options can be rapidly deployed and deliver impact. Otherwise, the field will squander time and money, with epidemic control slipping further out of reach.
  • With US funding cuts to both HIV prevention R&D and delivery, communities must be engaged, supported, and informed about all prevention options, and the choices that all stakeholders will need to make. This means gathering and sharing data and information about cost-effectiveness, user acceptability, program feasibility, and impact. Communities empowered with the facts can advocate for the choices they need, and push ministries of health to make strategic investments and procure the prevention method mix that fits their context and delivers impact.

Prevention Playlist

AVAC develops a wide range of resources to inform decision making and action. Check out the latest:

Join

  • Subscribe to Global Health Watch: AVAC’s weekly newsletter dedicated to breaking down critical developments in US policies and their impact on global health, at avac.org/global-health-watch
  • CHANGE: In response to the unfolding crisis, more than 1,500 people from civil society organizations around the world have launched CHANGE—Community Health & HIV Advocate Navigating Global Emergencies—a coalition formed to support urgent action: [email protected]

Use

Watch/Listen

Read

An “Innovation Pile-Up” in Next-Generation LA-PrEP is Possible

The HIV prevention market is headed toward a period of significant opportunity—and possible congestion—as a slate of new products are on track for continued development and potential introduction to the market in 2027 and 2028. Markets and policies must be built to support the products in the market already, so that new options can be rapidly deployed and deliver impact. Otherwise, the field will squander time and money, with epidemic control slipping further out of reach. Excerpted from PxWire.

Years Ahead in HIV Prevention Research: Time to Market

This timeline shows the potential time points when the next-generation of HIV prevention options might find their way into new programs.

Lenacapavir Regulatory Approval

Regulatory approvals, pending decisions, and appeals as of March 2025. For product approvals, volumes, implementation, and price comparisons of long-acting PrEP, visit our dashboard on PrEPWatch.org.