Landmark Trial in South Africa and Uganda Finds Twice Yearly HIV Prevention Injection Safe and Highly Effective

AVAC Calls for Accelerated Regulatory Review and Ambitious Introduction Plans

AVAC welcomes the groundbreaking results of the PURPOSE 1 HIV prevention study among adolescent girls and young women in South Africa and Uganda. Preliminary safety and efficacy results were reported today by Gilead Sciences, the developer of the lenacapavir, one of the HIV prevention drugs that was being studied in the trial. An independent data and safety monitoring board (DSMB), at a scheduled review of the trial data, found the regimen to be safe and highly effective, with no infections seen among trial participants who received injectable lenacapavir. 

“This is one of the most important results we’ve seen to date in an HIV prevention study,” said Mitchell Warren, AVAC’s executive director. “Adding additional HIV prevention options means more people may find an option that is right for them. Beyond expanded choice, a twice-yearly injection has the potential to transform the way we deliver HIV prevention to people who need and want it most – from an easier to follow regimen for individuals to a decreased burden on healthcare systems that are stretched to the limit.” 

“We are incredibly excited about this result, especially about what it can mean for women in Africa,” says Nandisile Sikwana, Regional Stakeholder Engagement Manager for AVAC, and a member of the PURPOSE 1 Global Community Advisory Group. “We applaud Gilead’s commitment to Good Participatory Practice in this and the other PURPOSE studies. While we wait for full data from the study, including adherence data of oral F/TAF, it is imperative that planning for rollout of lenacapavir be accelerated. We know that even with the most ambitious timeline, it will take time for lenacapavir to be rolled out,” says Sikwana.

The PURPOSE 1 study enrolled over 5,300 cisgender adolescent girls and young women ages 16-26 in South Africa and Uganda. The study is evaluating injectable lenacapavir for PrEP and daily oral emtricitabine/tenofovir alafenamide (F/TAF) for PrEP. A companion trial, PURPOSE 2, is underway in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the US, testing twice-yearly lenacapavir for PrEP among cisgender men who have sex with men, transgender women, transgender men, and gender non-binary people. Results from PURPOSE 2 are expected by early 2025. Additional studies in critical populations, including PURPOSE 3 among cisgender women in the US and PURPOSE 4 among people who use injection drugs, are also underway, and it will be imperative to understand how today’s results influence these trials. A schematic of the suite of studies is here.

Gilead’s plans for submission to regulatory agencies and future access, including the US Food and Drug Administration (FDA), are not yet clear. But the results reported today make this urgent. “We expect to see a timeline that takes into account a full analysis of PURPOSE 1 data and the coming data from PURPOSE 2 from Gilead as soon as possible, and we urge regulatory agencies to prepare to fast track regulatory review,” Warren said. “We also call on WHO to be prepared to quickly include lenacapavir, if approved by regulatory agencies, in HIV prevention guidelines. There is no time to waste if we are to translate these exciting clinical trial results into actual public health impact and expand the toolbox of HIV prevention choices.”

“We now know that lenacapivir for PrEP is safe and highly effective among women,” Sikwana added. “Even as we await the results of the trial among other essential populations and for regulatory submission and review, there is urgent work to be done now by communities, policy makers, funders and program implementers to design and build HIV prevention programs and prepare health systems to deliver the growing array of biomedical PrEP options, including the addition of twice-yearly injectable lenacapavir. The full range of PrEP products – including oral PrEP – must be made feasible choices for all people who need and want HIV prevention options.”

Lessons learned from roll out of daily oral PrEP, and more recently the dapivirine vaginal ring and injectable cabotegravir, can help speed regulatory approval and guideline development in key countries, design of effective programs, and community understanding of and acceptance of lenacapavir for PrEP.

“AVAC and a cadre of international partners have been working together to plan for successful, accelerated introduction of lenacapavir. Since oral PrEP was first shown to be safe and effective 14 years ago, the global health community has failed in delivering PrEP at scale and with equity – and we have, therefore, not seen the impact that we need. The lessons from the past are clear, and we now must act on them and move with speed, scale and urgency. There can be no excuses and no delays,” said Warren. “We look forward to working with civil society partners, Gilead, international donors, normative agencies and national governments to ensure that this groundbreaking HIV prevention option is made available as quickly as possible and that we don’t squander this opportunity to drive down new HIV infections.”

Avac Event

You Get What You Measure: Why Monitoring for PrEP Choice Helps Tell Our Story

The data we collect on a program determines its path and priorities. This webinar will cover the current state of PrEP M&E and efforts to improve and simplify the data we collect, allowing our data to better reflect how people are using PrEP, support PrEP choice amongst the growing array of PrEP methods, and enhance the stories we can tell about PrEP program implementation.

Presenters:

  • Katharine Kripke, Avenir Health, MOSAIC
  • Jessica Williamson, Avenir Health, MOSAIC

Panelists:

  • Omolabake Ekundayo, Ministry of Health Nigeria
  • Dr. Herbert Kadama, Ministry of Health Uganda
  • Ramatsoai Soothoane, Jhpiego, MOSAIC Project Lesotho

Moderator:

  • Adaobi Olisa, FHI360, MOSAIC Project Nigeria

This webinar will offer live French and Portuguese translation, courtesy of the South-to-South Learning Network in Africa.

Co-sponsors:

  • BioPIC
  • South-toC-South Learning Network
  • The MOSAIC Project

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.

Tracking PrEP Rollout & Learning Lessons

Accelerating the rollout of the full range of proven HIV prevention options depends on learning from what’s been done in the past and investing in coordination and innovation to put improved solutions in place. The Biomedical Prevention Implementation Collaborative (BioPIC) is doing just that. Over the last two years, BioPIC—a project led by AVAC with support from the Gates Foundation—has been gathering and sharing evidence on these critical lessons to ensure the next generation of HIV prevention products reaches everyone who needs and wants them with much greater speed and equity.  

What We’re Learning—Highlights from 2024 Convenings

An ongoing series of think tanks, convened by BioPIC and WHO since 2021, are generating key insights for people-centered product delivery. Below, read the latest reports from these think tanks that are informing decision-making on priorities for accelerating access to PrEP. Go to the BioPIC’s page on PrEPWatch to find reports on all think tanks since 2021.  

  • Early Insights from EBONI and PILLAR, February 2024: Early insights from ViiV Healthcare, the manufacturer of CAB for PrEP, from two CAB for PrEP implementation studies, EBONI and PILLAR. Conducted by ViiV in the US, these are among the first studies gathering data in real-world settings. Learn more
  • Taking Stock of PrEP Evidence, March 2024: An analysis of current data and priority evidence gaps. This inquiry was not focused on any one PrEP product, and its findings are informing the focus of future think tanks. Learn more
  • Linking Modellers with the Latest Implementation Science Evidence, March 2024: A consideration of the latest modelling data and insights on injectable cabotegravir (CAB) for PrEP. Read about the biggest takeaways from CAB for PrEP modelling here, and learn more about the big questions that require further inquiry here
  • Discussing Early Results from the SEARCH Dynamic Choice Study, April 2024: Professor Moses Kamya of Makerere University shares early insights from the SEARCH Dynamic Choice Study in Kenya and Uganda, which gave participants a choice between oral PrEP, PEP, and CAB for PrEP, and analyzes the role of choice in PrEP coverage. Watch here
  • PrEP and the Role of HIV Self-Testing, May 23: Highlights from the WHO guidance on use of self-testing (HIVST) as an innovative way to increase PrEP access and coverage and further simplify PrEP delivery. Panelists also share experiences with procurement, costing, rollout and scale-up. Watch Here

As other new biomedical HIV prevention products roll out, BioPIC will continue to hold strategic convenings, identify and address evidence gaps, and work to accelerate equitable product introduction. To learn more efforts to coordinate the introduction of CAB for PrEP, check out the JIAS article Shaping and coordinating the implementation science agenda for injectable cabotegravir for PrEP: the role of the Biomedical Prevention Implementation Collaborative (BioPIC). To learn what’s needed to better coordinate rollout for not-yet-approved products in Phase III clinical trials, check out BioPIC’s Adaptable Product Introduction Framework

We hope you will book mark these resources, and stay up to date on findings from future think tanks and webinars in 2024 on the BioPIC page of PrEPWatch.

PxWire Volume 14, Issue No. 2

A Quarterly Update on HIV Prevention Research

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

New research provides reassuring evidence that oral PrEP can reliably prevent HIV infection in cisgender women even with non-perfect adherence. Prior to becoming the director of NIAID, Dr. Jeanne Marrazzo led a team in a study assessing the effectiveness of F/TDF for PrEP (brand name Truvada) among cisgender women across a wide range (11) of studies. This paper—HIV Preexposure Prophylaxis with Emtricitabine and Tenofovir Disoproxil Fumarate Among Cisgender Women, which she also presented on a recent Choice Agenda webinar—dramatically shifts the conversation away from the need for women to be “super-adherers” to oral PrEP. The data also reinforce the need to support an array of options for women.

These graphics show the very high effectiveness of oral F/TDF for women with daily adherence and also for those who had consistently high adherence. Data comes from 11 demonstration projects of 2,954 cisgender women across six countries (Botswana, India, Kenya, South Africa, Uganda, USA) over eight years (2012-2020).

The data also demonstrates comparable effectiveness of F/TDF found in cisgender men who have sex with men (MSM).

Global and Country Milestones

January-March 2024

  • Global cumulative PrEP initiations surpassed 6.7 million, which includes CAB initiations (12,075) and DVR initiations (1,797).
  • Mexico and the United Arab Emirates approved oral F/TAF (or Descovy) in April.

For more comprehensive PrEP initiation data, see our tracker, data.prepwatch.org.

PrEParing for New Products

It has taken over a decade from positive efficacy results for daily oral TDF/ FTC to reach scale globally—and six years post-efficacy just to become available, in limited quantities, in lower-and middle-income countries (LMIC). During this time, nearly 20 million people acquired HIV. How many of those infections would have been prevented with faster, more efficient rollout of PrEP?

The rollout of oral PrEP demonstrates that people don’t take PrEP simply because it’s available—there needs to be a demand for it, and it needs to be accessible, acceptable and used effectively by those who need and want it. These are the lessons the field is applying to the rollout of the dapivirine vaginal ring (DVR) and injectable cabotegravir for PrEP. To reach the UNAIDS target of 10 million PrEP users by 2025, initiations of oral PrEP alone will not be enough—and the graphic at right does show that the field is beginning to apply past lessons to accelerate introduction of injectable cabotegravir.

Having multiple options for users to choose from is critical to increasing PrEP coverage, as seen from the early results of the SEARCH dynamic choice study, where coverage among participants featured a choice of products and settings for receiving oral PrEP, PEP, or injectable cabotegravir. The study showed 70% PrEP coverage in contrast with 13% coverage among those only offered oral PrEP or PEP from standard programs.

Product Updates

  • So far this year, Canada, Mozambique, Tanzania, and the United Kingdom approved injectable cabotegravir, and it’s now under review in Taiwan.
  • Malawi, Zambia and Zimbabwe are the second, third and fourth countries now rolling out injectable CAB outside the planned and ongoing implementation science studies. This is due to initial quantities supplied via PEPFAR.

See AVAC’s integrated study tracker for more at prepwatch.org/resources/product-introduction-country-planning-matrix.

The Latest R&D in the Prevention Pipeline

The PURPOSE efficacy trials are expected to report results later this year or in early 2025. If the six-monthly injectable lenacapavir demonstrates safety and efficacy, it will be the next long-acting injectable PrEP option to enter the market—and it is not too early to plan.

  • PURPOSE 1 is evaluating the safety and efficacy of both twice-yearly injectable lenacapavir and daily oral F/TAF in cisgender women in South Africa and Uganda.
  • PURPOSE 2 is assessing injectable lenacapavir among cisgender men who have sex with men, transgender men, transgender women and gender non-binary individuals who have sex with partners assigned male at birth in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States.
  • PURPOSE 3 is studying injectable lenacapavir for PrEP among cisgender women in the United States who are disproportionately affected by HIV, with a focus on Black women and other women of color.
  • PURPOSE 4 is evaluating injectable lenacapavir in adults who inject drugs in the United States.
  • PURPOSE 5 will evaluate injectable lenacapavir compared to F/TDF in people who may benefit from PrEP but who are not currently taking PrEP in Europe. The study has an intentional focus on recruiting participants from groups across France and the United Kingdom that are disproportionally affected by HIV and often underrepresented in clinical trials.

Prevention Playlist

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

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Oral PrEP in Cisgender Women

Displayed in these two graphics: researchers documented patterns of adherence for oral PrEP and we graphed HIV incidence based on weekly F/TDF adherence in cisgender women. Excerpted from PxWire.

Moving a Product to the Real World

The rollout of oral PrEP demonstrates that people don’t take PrEP simply because it’s available—there needs to be a demand for it, and it needs to be accessible, acceptable and used effectively by those who need and want it. These are the lessons the field is applying to the rollout of the dapivirine vaginal ring (DVR) and injectable cabotegravir for PrEP. To reach the UNAIDS target of 10 million PrEP users by 2025, initiations of oral PrEP alone will not be enough—and this graphic shows that the field is beginning to apply past lessons to accelerate introduction of injectable cabotegravir.

Excerpted from PxWire.

An Overview of Lenacapavir for PrEP Trials

The PURPOSE efficacy trials are expected to report results later this year or in early 2025. If the six-monthly injectable lenacapavir demonstrates safety and efficacy, it will be the next long-acting injectable PrEP option to enter the market—and it is not too early to plan. Excerpted from PxWire.

PrEP Initiations by Country Worldwide

AVAC tracks global PrEP use by conducting quarterly surveys of ongoing oral PrEP demonstration and implementation projects, and collecting data from manufacturers and government agencies. This graphic shows data on PrEP initiations around the globe. For more trends in oral PrEP uptake, visit PrEPWatch.

Avac Event

Illinois PrEP Summit 2024: Disrupting Disparities and Advancing Access

The conference focuses on advancing biomedical HIV prevention to help achieve Getting to Zero by 2030. Key summit goals include improving access, addressing disparities, fostering research and promoting community engagement. Join us for in-person sessions covering strategies, policies and implementation research.

This conference is curated by AFC, MATEC, PrEP4Teens and Project VIDA.

Registration closes, June 7, 2024.