Regulatory review and introduction plans must be accelerated

AVAC enthusiastically welcomes the news that another trial of the long-acting, injectable antiretroviral cabotegravir (CAB-LA) for HIV prevention for HIV pre-exposure prophylaxis (PrEP) has demonstrated safety and efficacy, this time among cisgender women. Today’s announcement from ViiV, the US National Institute of Allergy and Infectious Diseases (NIAID), and the HIV Prevention Trials Network (HPTN) is based on a scheduled review by an independent data and safety monitoring board (DSMB) of the HPTN 084 study. Data reviewed by the DSMB found that CAB-LA provided significant protection from HIV. The trial also re-confirmed the safety and efficacy of daily oral TDF/FTC (brand name Truvada). Earlier this year, HPTN 083, a companion trial of CAB-LA among cisgender men and transgender women who have sex with men, reported similar results.

“This is extremely encouraging and exciting news for women around the world,” said Maureen Luba Milambe, AVAC’s African Regional Advocacy Advisor. “We congratulate the trial team and thank especially the more than 3,200 women from Botswana, Eswatini, Kenya, Malawi, South Africa, Uganda and Zimbabwe, whose participation in the study provided this important advance for HIV prevention.”

Data from the trial showed a clear protective benefit from cabotegravir, with an 89% percent risk reduction compared to oral TDF/FTC for PrEP. Overall incidence in the study was 1%, with 1.79% percent in the daily oral PrEP arm and 0.21% in the CAB-LA arm. Of 38 total HIV infections in the study, only four occurred among women who were receiving cabotegravir. Importantly, even though the rate of HIV infection was higher among women taking daily oral PrEP, 1.79% was the lowest incidence among women in a randomized trial of daily oral PrEP to date, underscoring the effectiveness of daily oral PrEP. Over the past 15 years, rates of HIV infection in HIV prevention trials in the region have consistently been closer to 4% when no active drug was provided. HPTN 084 demonstrates that both oral and injectable PrEP are safe and effective options.

As reported today, the HPTN 084 DSMB recommended that the blinded, randomized portion of the study be stopped early and all trial participants be told which active drug (CAB-LA or oral TDF/FTC) they were receiving as part of the study. The study will continue to completion with all participants being offered their preferred product.

“We now know that CAB-LA is highly protective against HIV for both men and women. The urgent work now is for policy makers, funders, program implementers and communities to design and build HIV prevention programs and health systems that can deliver the growing array of biomedical PrEP options, including oral, vaginal ring and injectable, and make them feasible choices for all people at risk of infection,” said Mitchell Warren, AVAC Executive Director. “This is essential work that can and must begin now, while we await further data, regulatory review and potential normative guidelines. Key to those efforts will be ensuring that we don’t repeat the delays that have slowed daily oral PrEP rollout over the past eight years.”

In preparation for the HPTN 084 study results, AVAC, along with a cadre of cisgender women in Africa, Europe and the US, have been working to identify potential issues, opportunities, challenges and concerns about the introduction of a new injectable HIV prevention product. This group will work with other networks of advocates for sexual and reproductive health and rights to continue to articulate an agenda for introduction of CAB-LA in the context of these welcome positive results.

“A new HIV prevention option for women is cause for celebration,” said Chilufya Kasanda Hampongo, a Zambian women’s health advocate with the Treatment Advocacy and Literacy Campaign (TALC). “We know that real choice depends on giving women—and all people—full information about risks and benefits, pros and cons of different methods, and of making sure that those methods are available for people to select from. An injectable will be a great choice for some people; for others, daily oral PrEP or the Dapivirine Vaginal Ring will be the right strategy for reducing HIV risk.”

“We must advance biomedical strategies in the context of comprehensive, community-led programs to deal with violence, stigma and discrimination. COVID-19 has shone a light on the epidemics of sexual and gender-based violence that help drive HIV,” said Yvette Raphael, Executive Director of Advocacy for Prevention of HIV and AIDS (APHA) in South Africa. “To be truly effective, injectable HIV prevention and other biomedical options must also be accompanied by investments in women-led work to break the cycles of violence in our societies.”

Advocates also emphasize the remaining need for significant work to understand how this new product can be effectively delivered in communities and among populations where it is most needed. Understanding user preferences, health system capacity needs, the price of the product and the programs that will deliver it, the potential risk of drug resistance and other issues are all critical parts of the puzzle that must be addressed as quickly as possible.

“In 2018, AVAC and the Clinton Health Access Initiative (CHAI) established the Biomedical Prevention Implementation Collaborative (BioPIC) to work with a wide range of stakeholders to develop an introduction plan for CAB-LA and other next-generation HIV prevention options. Today’s announcement gives new urgency to that work of translating promising research results into public health impact,” said Jessica Rodrigues, AVAC’s Director of Product Introduction and Access. “Operational research to find out how communities and individuals can best be supported to access the drug, and how health systems can be strengthened to deliver it should it be approved for use, is a critical next step and planning must begin now,” said Rodrigues.

Additional HPTN research is ongoing and is needed to understand safety and efficacy of CAB-LA for prevention among adolescent girls and pregnant and breastfeeding women, populations that are often at increased risk for HIV infection. In addition, while oral PrEP, the vaginal ring, and now injectable PrEP expand potential options, continued research is still needed on additional methods to expand options that can meet the needs of all populations.

“People need choices for HIV prevention that will work in their lives,” Luba Milambe added. “As we continue the work to increase access to daily oral PrEP, and plan for regulatory review and introduction of the Dapivirine Vaginal Ring, today’s exciting news on cabotegravir brings us another step closer to ensuring more real choice for effective HIV prevention.”

Over the weekend, we at AVAC and allies around the world witnessed history and gained hope as the results of the American presidential election (finally) got announced. To see a President who has already pledged to work to build public health and justice and trust science—and to roll back the Global Gag Rule—in 2021, along with a Black American, Indian-American woman in the White House! We have much to celebrate and much to do.

News also came in that the HPTN 084 trial of injectable long-acting cabotegravir for HIV prevention in cisgender women found a high level of effectiveness at a scheduled interim data review.

• Click here for AVAC’s press release.
• Click here for ViiV’s press release.
• Click here for NIAID’s press release.
• Click here for HPTN’s press release.
• Click here for background on CAB-LA.

Cisgender women receiving the injection had very low rates of new HIV diagnoses compared to cisgender women taking daily oral PrEP. Importantly, women in the daily oral PrEP arm also had low rates of HIV, with initial analysis of blood-drug levels showing that many participants in the oral PrEP arm were taking the daily dose as prescribed.

Bottom line: Both injectable CAB-LA and daily oral PrEP are safe, effective strategies for reducing HIV risk in cisgender women. These data concur with data on both strategies in gay men, other men who have sex with men and transgender women.

The American election results and the trial results have more in common than timing alone. Effective public health programs require much more than effective products. The urgent work now is for policy makers, funders, program implementers and communities to design and build HIV prevention programs and health systems that can deliver the growing array of biomedical PrEP options, including oral PrEP, the Dapivirine Vaginal Ring and, hopefully, CAB-LA, and make them feasible choices for all people at risk of infection.

AVAC looks forward to working with all stakeholders to advance and articulate priorities and recommendations to forge one comprehensive agenda that reduces HIV risk and expands human rights for all. Stay tuned.

Updates to AVAC’s Global PrEP Tracker are in for Q3 2020, showing that overall global uptake continued to climb even in the midst of COVID-19. The number of people who have started on PrEP has reached 773,474, an increase of more than 23 percent since the year began. This figure includes countries where the burden of HIV is high, such as Kenya and South Africa, and despite the impact of COVID-19 on healthcare systems.

Find details for every country with a PrEP program in the Excel version of the Tracker, and take a look at Australia, Kenya, South Africa, Uganda and Zambia to see trends in countries with notable increases in new PrEP users.

For a dynamic look at the data, use our data visualization tool depicting progress over time and by country. Seventy-eight countries—inclusive of all with a known PrEP program—contribute to the data set, updated quarterly via surveys to programs, demonstration projects, clinical trials and other PrEP initiatives.

If you have an update to share, please be in touch!