PxWire Volume 14, Issue No. 4

PxWire is AVAC’s quarterly update covering the latest in the field of biomedical HIV prevention research and development, implementation and advocacy. Each issue includes updates, emerging issues and upcoming events. A PDF version of this report is also available.

Progress in PrEP Uptake

The HIVR4P 2024 conference, hosted this year in Lima, Peru, put a spotlight on PrEP delivery in Latin America. Since 2019, rates of HIV acquisition in the region have been trending upward, from 110,000 annually in 2019 to approximately 120,000 in 2023. At the same time, Latin America has taken strides to combat this trend, from increasing PrEP initiation rates to preparing for longer acting PrEP products, such as injectable cabotegravir (CAB) and lenacapavir (LEN).

  • At least 15 Latin American countries have approved oral PrEP. Brazil and Peru also approved CAB for PrEP, and it is under review in Chile, Mexico, and Colombia.
  • Four countries and one territory in the region, Argentina, Brazil, Mexico, Peru, and Puerto Rico, have trial sites participating in the PURPOSE 2 trial, which showed LEN reduced HIV incidence by 96% compared to a background incidence, with 2 incident cases among 2,180 participants receiving LEN.
  • Latin American countries account for 306,000 cumulative PrEP initiations in the Global PrEP Tracker as of Q2 2024, which represent 4% of the global total.
  • Since 2019, PrEP initiations across the region continue to increase at a steady rate, with Brazil reaching about 194,000 cumulative PrEP initiations (63% of regional total) since the inception of its National PrEP Program.

Latest Trends in PrEP Uptake?

Find the latest trends on 2024 data in AVAC’s Global PrEP Tracker. Watch for the next update on November 22.

PrEParing for New Products

  • On October 2, Gilead Sciences announced six licenses to generic manufacturers in Egypt, India, and Pakistan to produce and market lenacapavir (LEN) for PrEP in 120 countries.
  • What’s new about this announcement? This marks an increase in speed, as compared to generic licenses for injectable CAB for PrEP. Gilead awarded these licenses even before submitting LEN for PrEP for regulatory approval in any country. Gilead’s license applies to 120 countries, which is more than the 90 countries covered by the generic license for CAB for PrEP. However, CAB for PrEP’s license also allows for generic supply in countries without patent barriers—by the time generic CAB for PrEP is available, this will be an additional 51 countries. Many countries with high HIV incidence have been left out of Gilead’s licensing deal; notably Argentina, Brazil, Mexico, and Peru, countries in which the PURPOSE 2 Phase III trials took place. In addition, Gilead’s licenses are more restrictive than ViiV’s, in terms of where generics can be marketed.
  • The timeline for generic LEN for PrEP to come to market is expected to be significantly shorter than for CAB for PrEP. Bioequivalence (BE) testing for LEN, which demonstrates a generic product works in the body in the same way as the originator product, is likely to be six months, versus the 18 months for CAB for PrEP, because of differences in the drug formulation. The rapid granting of voluntary licensing by Gilead also contributes to this shorter timeline.
  • Generic regulatory approval submission for LEN for PrEP may begin as early as the second half off 2026, two years after Gilead announced positive trial results. Generic CAB for PrEP is on track to submit for regulatory approval around the same time, approximately six years after the announcement of trial results.

Product Updates

  • CAB for PrEP has been approved in Cote d’Ivoire, Kenya, Myanmar, Namibia, and Ukraine. See AVAC’s Planning Matrix for more!

The Latest R&D in the Prevention Pipeline

Launched at HIVR4P in Lima, Peru in October 2024, the People’s Research Agenda (PRA) is a collaboratively developed framework for aligning the needs and priorities of affected communities with the agenda for HIV prevention research. 130 advocates from more than 20 countries contributed to the framework, which offers guidance on both research conduct and what products to develop.

PRA priorities include:

  • Support a choice-based prevention agenda with clear and realistic target product profiles that reflect the current and future landscape of HIV prevention. Begin with the end in mind by identifying and anticipating trial design issues (feasibility, cost, size, regulatory pathways) and implementation science questions so that the timeline from evidence to impact and to widespread access is as short as possible. Initiate access planning during efficacy trials to ensure expeditious rollout.
  • Center and invest in social and behavioral science that explores end users’ needs and preferences, informs target product profiles, and identifies and addresses social and structural barriers in HIV prevention.
  • Maintain advocacy across product categories to fill important gaps in a comprehensive HIV prevention toolbox. We must make newly efficacious products accessible, and vaccines, bnAbs, implants, and other products in early-phase development will also play an important role for a sustainable end to the epidemic.

Key considerations:

  • Invest in continuous learning so that advocates and communities where research is planned are equipped to weigh in on complex and evolving trial designs and approaches.
  • Novel trial designs using external controls are important in developing new prevention products. However, they must meet the rigorous standards of randomized controlled trials (RCTs) to ensure they provide reliable answers to key research questions without compromising quality.
  • Trial designs must address the needs and concerns of highly impacted communities.
  • Products moved into trials should be ones that fill community-informed gaps, such as improving upon existing prevention methods with innovations in cost, mode of delivery, duration or level of protection and other parameters.
  • Participants should be supported to clearly understand how novel design elements, such as run-in or opt-out phases, may impact their involvement.
  • Ensure that regulators are prepared to review and react to the data generated by future trials, especially if it is a novel design.

The PRA is a living document—emerging priorities, challenges and opportunities will be reflected in ongoing updates. Please share your thoughts, reflections, and comments by emailing Grace Kumwenda at [email protected]. For more information on the People’s Research Agenda visit avac.org/peoples-research-agenda.

Prevention Playlist

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

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PxPulse: The Advocacy Chronicles with Danielle Campbell from PrEP in Black America

In this episode of the Advocacy Chronicles, we’re putting the spotlight on the US, on the dismal statistics on access to PrEP in Black communities, on the state of HIV prevention among Black Americans overall, and the work of one advocacy group— PrEP in Black America (PIBA). Danielle Campbell is one of the founders of PIBA and a long-time advocate for HIV prevention and health equity. She joins the Advocacy Chronicles to talk about PIBA’s call to action for an HIV research agenda that prioritizes the needs of Black communities. And we also explore the tactics that have led this group to quickly rise as a powerhouse, bringing together communities and government to find solutions that improve the US HIV response.

Danielle is a member of the research faculty at the Charles R. Drew University of Medicine and Science and a member of the community scientific subcommittee for a global HIV research network. She is an experienced clinical research manager who integrates principles of health equity and implementation science into biobehavioral research into HIV treatment, prevention and cure research and she is a past Chair of the HIV/AIDS Section of American Public Health Association (APHA) and has served as Chair of the Science Board and Co-Chair of the Joint Policy Committee.

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From Clinical Trial Efficacy to Public Health Impact: A Plan for Accelerating Access to Injectable Lenacapavir for PrEP

This plan provides a broad view of all the moving parts and identifies actions and actors responsible for ensuring time is not wasted and opportunity not squandered.

Advocates’ Guide to Multipurpose Prevention Technologies (MPTs)

Multipurpose prevention technologies (MPTs) are products designed to simultaneously address more than one sexual and reproductive health concern. This advocates’ guide shows the pipeline of products in development, discusses why MPTs are needed, investment, and what advocates can do to push for MPT development and introduction.

The Lens on LEN

The Basics on Injectable Lenacapavir as PrEP

In 2024, Gilead Sciences released findings from the PURPOSE 1 and PURPOSE 2 trials testing lenacapavir (LEN) as HIV prevention. The PURPOSE 1 trial found 100% efficacy in preventing HIV in 5,300 cisgender women in Uganda and South Africa, and the PURPOSE 2 trial showed a 96% reduction in HIV incidence among cisgender men, trans, and non-binary individuals across multiple countries. Both trials demonstrated LEN’s safety and effectiveness in reducing HIV transmission. This advocates’ primer provides background on the product and trials; a summary of the early findings of PURPOSE 1 & 2; key questions and next steps.

Download the report.

Sexual and Reproductive Health Integration Advocacy Roadmap

This roadmap addresses the critical need for integrated sexual and reproductive health (SRH) and HIV services. This integration is essential for enhancing public health outcomes, socio-economic benefits, and individual health and rights. The Roadmap aims to revitalize and sustain advocacy efforts for SRH and HIV integration, empower communities to hold stakeholders accountable for implementation, increase political and program support to enable the shift from policy to practice, and foster dynamic partnerships across research, advocacy, implementation, and policy sectors.

It was developed by Copper Rose Zambia (CRZ) as part of the Coalition to Accelerate and Support Prevention Research (CASPR). It draws on extensive input, including desk reviews, interviews, focus group discussions, and a specialized workshop held at the 2023 International Conference on AIDS and STIs in Africa (ICASA).

Lenacapavir: The case for investing in delivering HIV prevention

The promise of long-acting PrEP has been super-charged this year by studies showing the powerful efficacy of an antiretroviral known as lenacapavir (LEN).

This episode of PxPulse goes deep on LEN for PrEP. Recorded just days before Gilead’s announcement that PURPOSE 2 also found very high efficacy, Dr. Flavia Kiweewa, a principal investigator of PURPOSE 1, the first trial to announce efficacy, lays out the research findings and what they mean. And Chilufya Kasanda Hampongo of Zambia’s Treatment Advocacy and Literacy Campaign and Mitchell Warren of AVAC talk about how to change a long history of squandered opportunities to get rollout right.

The PURPOSE1 trials announced findings in June that a twice-yearly injection of LEN was 100% effective among cisgender women, with zero new cases of HIV. And the PURPOSE 2 trial among cisgender men, and trans and non-binary people, was shown to reduce the risk of HIV by 96%.

LEN now enters a select category, one of five ARV-based options for PrEP that all protect against HIV if you take them. But many of the people applauding the results from PURPOSE 1 and 2 will tell you that breakthrough science like this is, as hard as it is, is still the easy part. To break the back of the HIV epidemic demands overcoming an altogether different challenge—coordinating and accelerating every step in rolling out new products so that everyone who needs HIV prevention can get it.

Listen to this podcast to learn what must be done to finally deliver on the promise of highly effective HIV prevention, from pills to rings to injectable PrEP and beyond.

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Second Pivotal Trial of Twice-Yearly HIV Prevention Injection Safe and Highly Effective

AVAC welcomes the groundbreaking results of the PURPOSE 2 HIV prevention study of twice-yearly injectable lenacapavir for PrEP among 3,200 cisgender men, transgender men, transgender women, and nonbinary individuals who have sex with partners assigned male at birth. Among more than 2,000 people in the trial who received lenacapavir, there were only two HIV infections.

PxPulse: An Advocacy Chronicle on U=U in South Africa with Mandisa Dukashe

On this episode of PxPulse: The Advocacy Chronicles, Mandisa Tyadi Dukashe, Treatment Technical Lead at the South African National AIDS Council (SANAC) describes her work in helping to inspire and launch a National U=U Campaign in South Africa in 2024.

What is U=U? Undetectable equals Untransmittable refers to a major breakthrough in the science and understanding of HIV treatment. From data published in 2019, researchers confirmed that people living with HIV who have an undetectable viral load and take medication as prescribed have zero risk of transmitting HIV to their sexual partners.

This evidence galvanized a worldwide campaign, with the hope that spreading the word, Undetectable equals Untransmittable, would reduce stigma around HIV and inspire people to maintain their treatment. 

The WHO released guidance in 2023 on how to monitor viral load, which provided supportive global policy for ministries of health. But WHO action is not enough to set public health policy or fulfill the promise of U=U.

Mandisa has long list of credentials behind her: She’s the co-founder of the U=U Africa Forum, part of the U=U Global Community Advisory Board, an alumnus of the AVAC Cure Research program and the AVAC Advocacy Fellows Program. Among many accolades, she has also been recognized as a 2021 Amazing People Living with HIV by HIV Plus Magazine.

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Resources

Harnessing private sector strategies for family planning to deliver the Dual Prevention Pill, the first multipurpose prevention technology with pre-exposure prophylaxis, in an expanding HIV prevention landscape

Working with colleagues, AVACers Cat Verde Hashim and Kate Segal published this research article in the Journal of the International AIDS Society. The researchers undertook qualitative research in Kenya, South Africa and Zimbabwe to prioritize private sector service delivery approaches for the introduction of the DPP.