People’s Research Agenda 

HIV prevention research and development (R&D) must remain a top priority in the HIV response, even as the global context for HIV funding, policies, and programs changes. Since the People’s Research Agenda (PRA) was launched in 2024, significant events have occurred, both advancements and setbacks:

Advancements

• Lenacapavir (LEN) has undergone an expedited regulatory approval process, with FDA approval in June 2025, followed by WHO guidelines in July and approvals by the EMA and multiple African countries between August and December. Plus, agreements with generic manufacturers are now in place to accelerate the introduction of LEN at lower prices beginning in 2027.
•  An investigational, once-monthly oral pill for HIV pre-exposure prophylaxis (PrEP)has entered efficacy testing under the EXPrESSIVE-10 and -11 trials in 17 countries, marking a major step forward in next-generation oral HIV prevention.
• The HIV Vaccine Trials Network (HVTN) launched six small-scale “discovery medicine” trials testing early, experimental vaccine candidates, in the face of ongoing funding threats at the US NIH.
• IAVI initiated C114, a Phase I trial in Zimbabwe and South Africa, testing a gorilla-adenovirus vector–based vaccine designed to elicit strong CD8 T-cell responses.

Setbacks

• Several promising trials and research programs were terminated, most notably USAID-funded HIV projects ADVANCE, BRILLIANT, MATRIX, and MOSAIC, researching early phase vaccines and novel ARV-based and multi-purpose products, as well as real-world  implementation of multiple PrEP options. These terminations end any PEPFAR support for HIV R&D after decades of advancement.
• The US NIH has cancelled a range of mRNA vaccine programs and posed threats to the Center for HIV/AIDS Vaccine Development (CHAVD) consortia.
• The funding landscape in which HIV prevention R&D occurs has significantly shifted due to cuts in foreign aid, US government shutdowns, and other political influences.
• Political actions have further destabilized the field; on February 7, 2025, the US Administration issued Executive Order #140204, halting US funding to South Africa and extinguishing prospects for future HIV prevention research support.

The People’s Research Agenda (PRA) was developed throughout 2024 in partnership with global advocates and communities. It proposes a people-centered framework for how HIV prevention products should be developed, tested, and introduced so that products meet the needs, preferences, and realities of the people most affected by HIV.

Now, AVAC is issuing the PRA’s first annual update, the 2025 PRA. To further ensure the PRA is a living document, the new interactive format provides an actionable tracker, an advocacy toolkit, and clear call to action for funders, researchers, advocates, communities, and policymakers to meet this critical moment.

Tracking What Matters

Accountability begins with accurate and accessible information. The PRA focuses on what products are moving forward, which are stalled, and which are at risk of disappearing altogether. By mapping progress across the prevention landscape, the PRA shows where investments align—or fail to align—with community priorities. By tracking the science, the PRA can reveal critical gaps in the ultimate “basket” of prevention products available to meet the needs of diverse populations.

More than a report and data tool, the PRA serves as a sentry for equity, a living accountability mechanism that seeks to transform information into influence and ensure that no community, or promising idea, is left behind.

PRA Pipeline Tracker

This tracker provides details on key HIV prevention trials to watch. It is updated on a quarterly and ad-hoc basis as developments occur. If you would like to share additional information or corrections, please email Breanne at [email protected].

People’s Research Agenda 2025 Update Summary Table

December 2025

Modality	Status (2025)	Gaps	2026 Priorities
ARV-Based Prevention	Ongoing rollout of daily oral, CAB, and DVR Ongoing momentum of LEN approvals, accelerated rollout and market shaping with potential introduction in 12 priority countries starting by Q1 2026 Launch of MK-8527 Phase III trials of monthly oral PrEP across 17 countries Research progress towards 12-month dosing cycles for LEN, as well as 4-monthly CAB and 90-day ring	Slow scale-up of proven options (oral PrEP, injectable CAB, DVR) Funding cuts are disrupting pipeline diversification Missing on-demand and short-acting products	Accelerate implementation and optimization of existing PrEP options Innovate using community-led delivery platforms and differentiated service delivery models Define market segmentation for multiple long-acting regimens Maintain community engagement and regulatory readiness for rapid rollout of new products Rebalance product pipeline GPP and ongoing engagement for the MK-8527 program
MPTs	Pipeline mostly in pre-clinical/early phase DPP is the most advanced MPT; Phase IIb study on acceptability ongoing Other MPT products stalled by USAID cuts including the MATRIX product pipeline	Funding uncertainty for key products, including vaginal film and fasting dissolving inserts Limited products for gender-diverse populations Complexities around manufacturing and regulatory pathways Limited integration of STI prevention	Develop an investment case to funders for paused MPT products Expand pipeline beyond ARV-based products, and cis-women population Engage regulators, WHO, and advocates early to define combination-product pathways Build on lessons learned from DPP market shaping considerations for future MPT products
Vaccines	Most studies in early phase, focus on germline-targeting, T-cell response, and mRNA approaches Six small HVTN trials have started despite threats of funding cuts Uncertainty about NIH support for HIV vaccine R&D, most notably evidenced by CHAVD threats ADVANCE and BRILLIANT programs terminated due to USAID cuts Growing vaccine hesitancy and mis- and dis-information	Lacking consensus on TPP Lack of clarity on interim milestones for success Risks to R&D infrastructure in high-burden regions Weakening political and public support	Align and socialize an updated HIV vaccine TPP Create a coordinated R&D roadmap with clear milestones Rebuild advocacy to sustain funding and to counter misinformation Invest in regulatory, trial, and manufacturing capacity in high-burden regions, especially in Africa, Asia, and Latin America
bNAbs	Ongoing progress toward combination bNAbs (“Combo AMP”) Early trials testing potency, breadth, and duration of different combos Ongoing focus on infant prophylaxis and combo formulations Attempts to define market pathways	Unclear role and use case in the market as an actual product Complex manufacturing and delivery No defined path for access or commercialization	Reach consensus on bNAb use cases and update TPPs Clarify development and regulatory pathways Define commercial-partner strategy Sustain civil-society dialogue on the potential role of bNAbs
Cross-cutting Issues	Funding contractions are reshaping priorities without community input Shifting focus to implementation science at the expense of discovery science and product development Complexity of conducting traditional randomized controlled trials in the current prevention landscape Widespread uncertainty and instability threaten future efforts	Invest across basic research, clinical trials, and implementation science, avoiding duplication and prioritizing unmet needs Embed meaningful community engagement and Good Participatory Practices at all stages of research, including trials and implementation Use adaptive and inclusive trial designs informed by community perspectives, with clear access plans for successful products Sustain an infrastructure for early-phase trials to enable future progress

Previous Edition of the People's Research Agenda