For the first time, the U.S. Food and Drug Administration (FDA) has approved a long-acting injectable agent for the prevention of HIV, an alternative to daily pills for HIV prevention and an important step forward in the quest for global HIV epidemic control.

ICAP at Columbia University played a valuable role in supporting the two studies that led to the FDA approval. HIV Prevention Trials Network (HPTN) 083, supported by ICAP’s Harlem and Bronx Prevention Centers, and HPTN 084, supported by ICAP in Eswatini, compared the safety and efficacy of long acting cabotegravir (CAB-LA) to daily oral tenofovir/emtricitabine (TDF/FTC) (Truvada) and demonstrated that CAB-LA injected once every eight weeks was superior to daily oral TDF/FTC among cisgender men and transgender women who have sex with men (HPTN 083) and cisgender women (HPTN 084).

The FDA approval of a long-acting injectable agent is a major milestone for strengthening the HIV prevention toolkit. While pre-exposure prophylaxis (PrEP) pills have gained traction in recent years, the medication’s strict daily adherence requirement for effectiveness has proven difficult or unrealistic for many, given factors such as poverty, homelessness, and depression. An injection needed only once every eight weeks could also help mitigate the social stigma often associated with HIV, as some individuals may find periodic injections more discreet than taking daily oral pills.

“The FDA approval of the long-acting injectable will mean a lot to our own Harlem and Bronx communities,” said Sharon Mannheimer, MD, Harlem Prevention Center site leader, “because it will open up access to another option for HIV prevention. This is particularly true for individuals who do not want to take a daily pill – either because of possible side effects, stigma, or adherence issues.”

While bi-monthly injections may be easier to adhere to, the ultimate benefit of CAB-LA is its effectiveness.

HPTN 084, which enrolled more than 3,200 cisgender women in Botswana, Eswatini, Kenya, Malawi, South Africa, Uganda, and Zimbabwe, demonstrated a 92 percent reduction in incident HIV infections in study participants given CAB-LA compared to TDF/FTC.

HPTN 083, which was the first study to compare the efficacy of CAB-LA to a daily oral pill, enrolled more than 4,500 cisgender men who have sex with men and transgender women who have sex with men in Argentina, Brazil, Peru, South Africa, Thailand, the United States, and Vietnam. The study’s findings demonstrated a 69 percent reduction in incident HIV infections in study participants given CAB-LA compared to TDF/FTC.

Clinic in Malawi

When taken daily, oral PrEP pills can reduce HIV infection up to 99 percent but given that people often skip or forget to take their pills, the long-acting injectable can help protect those missed doses and reduce new HIV infections.

“Just as there has been development of long-acting contraceptive methods instead of pills that must be taken daily or are coitally dependent methods, alternatives to daily pills for HIV prevention must be explored,” said Ann Khan, MPH, MSN, senior site clinician at the Bronx Prevention Center. “Current studies are investigating implants, intravaginal rings, and other injections for PrEP.  Looking ahead, we must continue to develop a diversity of long-acting options for PrEP. It is crucial to increase choice and address the barriers related to adherence and long-term use of HIV prevention methods.”

Beyond the Bronx and Harlem, the long-acting injection could hold major implications for sub-Saharan Africa as well. While CAB-LA is not yet widely available in Eswatini, the results of HPTN 084 demonstrate evidence for engaging sponsors in discussions on the availability of HIV prevention alternatives to daily pills, especially as a strategy for protecting women against HIV acquisition.

“We are at a critical juncture on the pathway to global epidemic control,” said Julie Franks, PhD, technical specialist in ICAP’s Clinical and Training Unit. “The COVID-19 pandemic took an enormous toll on our progress toward reducing new HIV infections and laid bare the weaknesses in our piecemeal approach to rolling out daily oral PrEP. As research sites for HPTN 083 and 084, we saw first-hand how many study participants struggled to balance the challenges of complex lives with adhering to bi-monthly PrEP injections. To realize the promise of long-acting injectable PrEP, prevention programs need to apply all the lessons learned about providing person-centered, differentiated models of care for people living with HIV. These include innovations in strategic information systems, approaches to counseling to help clients choose the prevention strategy that works for them, and support for providers to retain clients in prevention services over time.”

At the recent AIDS 2022 conference in Montreal, Canada, researchers from the HPTN presented updated results from the HPTN 084 study, demonstrating reductions in HIV incidence were sustained in the year following the study and confirming a high level of protection against HIV acquisition among study participants.

About ICAP

A major global health organization that has been improving public health in countries around the world for nearly two decades, ICAP works to transform the health of populations through innovation, science, and global collaboration. Based at Columbia Mailman School of Public Health, ICAP has projects in more than 30 countries and is working side-by-side with ministries of health and local governmental, non-governmental, academic, and community partners to confront some of the world’s greatest health challenges. Through evidence-informed programs, meaningful research, tailored technical assistance, effective training and education programs, and rigorous surveillance to measure and evaluate the impact of public health interventions, ICAP aims to realize a global vision of healthy people, empowered communities, and thriving societies.

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