HVTN researchers and ethicists say findings will help guide new approaches to HIV vaccine studies
SEATTLE (Wednesday, January 18, 2023) – A Phase 3 study of an investigational HIV vaccine regimen has been discontinued following a planned, interim review by the study’s independent Data and Safety Monitoring Board (DSMB) on Jan. 12, 2023.
The Mosaico study – also known as HPX3002/HVTN706 – is a Phase 3 study conducted by the HIV Vaccine Trials Network (HVTN), based at Fred Hutchinson Cancer Center in Seattle, with a consortium of global partners, inclduing the Desmond Tutu Health Foundation in Cape Town, South Africa.
The study aimed to test a “mosaic”-based HIV vaccine in multiple countries around the world among cisgender men and transgender people who have sex with cisgender men and/or transgender people. Mosaic vaccines are intended to trigger a broader immune response than earlier vaccine models by including genetic material from a variety of HIV strains prevalent around the world. In its review, the Data and Safety Monitoring Board said the investigational vaccine was generally safe and well tolerated; however, it was not effective at preventing the acquisition of HIV-1.
One of the unique features of the study was that as part of the community outreach, clinic staff members first engaged and assessed community acceptance of, and interest in, HIV pre-exposure prophylaxis (PrEP). If community members accepted PrEP, they were navigated to services to begin receiving the preventive medication. However, if community members did not accept PrEP, they were considered for the study. Participants who joined the study and later changed their mind about PrEP were also navigated to PrEP services and remained in the study.
Mitchell Warren, executive director of AVAC and a member of the Governing Council of the International AIDS Society, said engaging diverse communities worldwide, providing education, and welcoming personal choice are all critical elements of HIV vaccine studies if researchers are to discover real-world answers in real-world situations.
“There is a worldwide demand for a range of effective and acceptable HIV prevention options, including especially HIV vaccines, particularly in communities where health care delivery may be limited, at best,” he said. “The study team emphasized the value of choice for participants, particularly in decisions regarding PrEP, which is becoming increasingly available globally but is not universally accepted. The Mosaico team’s focus on inclusion and the design of the study to respect participants’ lifestyles and choices provided an opportunity to increase representation from populations most vulnerable to HIV. The ethical and community-friendly design and conduct of this study has helped to build trust in communities that may not be inclined to trust research institutions.”
The Phase 3 Mosaico study began in 2019. In September 2021, it reached full enrollment of approximately 3,900 cisgender men and transgender people who have sex with cisgender men and/or transgender people, who are at increased vulnerability to HIV acquisition. There are more than 50 trial sites in Argentina, Brazil, Italy, Mexico, Peru, Poland, Spain and the U.S.
The primary analysis of the Phase 2b Imbokodo study, which evaluated an investigational HIV vaccine regimen that was similar to Mosaico, found that the vaccine regimen did not provide sufficient protection against HIV in a population of young women in sub-Saharan Africa. The Imbokodo regimen was found to be generally well tolerated with no serious adverse events. Those findings were announced in August 2021.
“Our experience with the Imbokodo study in sub-Saharan Africa supports anecdotal evidence and other recent findings that many people – including many women in this study – do not choose or accept oral PrEP for their HIV prevention needs. In addition to providing insight into the decisions being made by patients and study participants, this further reinforces the critical importance of choice in HIV prevention strategies and HIV vaccine discovery,” said Dr. Linda-Gail Bekker, director of the Desmond Tutu HIV Centre.
Mosaico was led by a global public-private partnership including Janssen Vaccines & Prevention B.V., the National Institute of Allergy and Infectious Diseases (NIAID), HVTN, and the U.S. Army Medical Research and Development Command (USAMRDC).