Often the most exciting advancements in global health come at unexpected times. Almost two years earlier than anticipated, a major clinical trial has shown that a bi-monthly injection is highly effective in preventing HIV in cisgender men and transgender women who have sex with men. Although results are pending from a critical sister study, HPTN 084, among cisgender women at risk for HIV in sub-Saharan Africa, these findings are a major leap forward in HIV prevention.
The HIV Prevention Trials Network (HPTN) announced on May 18, 2020, results from HPTN 083, a global study that compared the safety and efficacy of long-acting injectable cabotegravir (CAB-LA) to daily oral tenofovir/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (oral PrEP).
Update: On July 7, it was announced at AIDS 2020 HPTN 083 study “results meet the statistical criteria for superiority of the regimen containing CAB compared to TDF/FTC [daily oral PrEP] in the HPTN 083 study population,” cisgender men and transgender women who have sex with men.
A long-acting injectable for PrEP that does not require adherence to an oral daily pill is a great addition to the HIV prevention toolbox.
-Dr. Beatriz Grinsztejn, HPTN 083 protocol co-chair
Both products use antiretroviral drugs as a way for HIV-negative people to reduce their risk of getting HIV. But since oral PrEP requires at-risk individuals to take pills on a daily or event-driven basis, a bi-monthly injection of CAB-LA may help people protect themselves more consistently due to decreased dependence on adherence.
The study showed that CAB-LA lowered HIV incidence, prompting an independent Data and Safety Monitoring Board (DSMB) to recommend the blinded portion of the study end. Participants, over 4,570 cisgender men and transgender women who have sex with men in Argentina, Brazil, Peru, South Africa,Thailand, the U.S., and Vietnam, will know which medication they received and have the option to continue on CAB-LA or TDF/FTC for oral PrEP.
“A long-acting injectable for PrEP that does not require adherence to an oral daily pill is a great addition to the HIV prevention toolbox,” said HPTN 083 protocol co-chair Dr. Beatriz Grinsztejn, in the HPTN 083 press release. “Prevention strategies have never been one-size-fits-all.”
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The early results from the clinical trial could have caught governments and other decision-makers who will be responsible for ensuring individuals at risk of HIV infection have access to CAB-LA, off guard. But together with AVAC and our partners, CHAI is working to make sure we can introduce the injection quickly and safely in low- and middle-income countries.
New tools to prevent HIV infection
Over the last two decades, CHAI, national governments, donors, researchers, healthcare providers, civil society, and other partners have worked together to make remarkable progress in fighting the HIV epidemic in high-burden low- and middle-income countries. Since 2004 AIDS-related deaths have dropped by a third, with 23.3 million living with HIV now on treatment, according to UNAIDS.
But more work is needed to increase access to HIV diagnostics, treatment, and prevention options.
Progress against the HIV epidemic remains tenuous as the annual number of new infections has only declined marginally – 16 percent between 2010 and 2018. An estimated 1.7 million people were infected in 2018. The burden of new infections falls disproportionately on populations such as men who have sex with men, transgender people, sex workers, people who inject drugs, and, in Sub-Saharan Africa, adolescent girls and young women.
Developing and providing access to safe, effective prevention options that meet the needs of these high-risk populations is essential to halting the spread of HIV. While effective interventions such as condoms, voluntary medical male circumcision, and oral PrEP have made an impact in some communities, each of these products has challenges.
CAB-LA still needs to receive regulatory approval. There is also work to be done to ensure that it is affordable for buyers in low- and-middle income countries. If we can ensure it reaches those most in need, CAB-LA could be an important, additional HIV prevention option that has the potential to significantly reduce the incidence of HIV around the world.
Because these research findings were shared two years earlier than originally expected, many who work in the HIV prevention community felt a jolt of excitement. But this research alone will not bring the product to those who need it most.
More: CHAI’s HIV new product introduction toolkit
Many questions remain about the injectable PrEP product, such as if it is safe and effective for cisgender women, if it will be cost-effective, and how health systems in low- and middle-income countries will adapt to provide an intramuscular injection.
In 2012 when research findings and normative guidance were released for oral PrEP in the United States, many low- and middle-income country governments and partners had similar questions.
Unfortunately, with oral PrEP, the global response was fragmented and uncoordinated, leading to a delay of nearly four years between regulatory approval in the United States and when the product was first approved in Africa in late 2015. With 65 percent of all new HIV infections occurring in Africa, this delay was a significant setback for the HIV prevention community and echoes back to the tremendous losses Africa experienced in the 1990s due to inequitable access to HIV treatment.
Learning from past product rollouts
Learning from the oral PrEP experience, CHAI, in collaboration with AVAC, the Bill & Melinda Gates Foundation, and ViiV Healthcare established the Biomedical Prevention Implementation Collaborative (BioPIC) in 2018 to forge a new path forward for HIV prevention. Using CAB-LA as our focus and example, BioPIC takes an innovative, collaborative approach to introduce new products.
More: Download our BioPIC factsheet
With BioPIC, we are planning for product introduction in parallel to clinical trials with the goal of shortening the time it takes for new HIV medications to roll out across low- and middle-income countries. We also coordinate with global and country decision-makers to ensure that rollout is well-funded, well-timed, and well-designed.
Over the last two years, CHAI, as BioPIC Secretariat, in collaboration with AVAC, has convened over 100 HIV prevention experts from over 20 countries and 80 civil society, donor, research, policy, normative, and implementation organizations. By reviewing decision-maker needs across the research-to-rollout continuum, BioPIC has developed a shared product introduction strategy for CAB-LA.
We believe that BioPIC can be transformational in accelerating new HIV prevention products from research to rollout – and ultimately help reduce new infections.
– Carolyn Amole, Senior Director of CHAI’s HIV Access Program
Without the BioPIC approach, the early results from the clinical trial may have caught partners off guard. But today the global community is ready to hit the ground running with a roadmap in hand.
Governments and partners are now well-positioned to begin assessing health system requirements to successfully introduce CAB-LA in low- and middle-income countries.
BioPIC will continue to serve as an essential network of collaborators. We will help partners coordinate on project details and ensure that the rollout is well-documented. BioPIC’s work with CAB-LA is setting a precedent for future HIV prevention products as we distill our strategy into an adaptable product introduction framework.
Carolyn Amole, CHAI Senior Director of the HIV Access Program, commented, “We were thrilled this week with the news from HPTN083, and we are eager for the HPTN084 trial among cisgender women in Africa to continue with urgency.
“We believe that BioPIC can be transformational in accelerating new HIV prevention products, like the cabotegravir injectable, from research to rollout – and ultimately help reduce new infections. Learning from the challenges of the past, through BioPIC we are calling on key stakeholders to come together to help prepare HIV prevention programs for rapid introduction of this product.
