African-led and coordinated out of Entebbe, Uganda, with international support, its success could mark the start of a new phase of vaccine development. Should it fail, it could also see immunologists give up on a generation of vaccines.
A novel trial that has been described as "the last roll of the dice" for a generation of HIV vaccines has entered its latter stages.
Called PrEPVacc, the trial is testing two vaccines alongside two forms of pre-exposure prophylaxis (PrEP) to test vaccine efficacy while offering protection to prevent the spread of HIV.
Nearly 40 years since HIV was identified as the cause of AIDS, and 36 years since the first HIV vaccine trial, the medical community still does not have a working vaccine. Although antiretroviral treatments are well established, access varies. UNAIDS estimates 630,000 people died from AIDS-related illness globally in 2022, while 39 million people are living with HIV, including 1.3 million people newly infected last year.
The hope is that PrEPVacc will succeed where other trials have fallen short – most recently HVTN 702 (dubbed "Uhambo"), halted in February 2020, HVTN 705 ("Imbokodo"), discontinued in 2021 and HVTN 706 ("Mosaico") in 2023, all of which were found to be safe but ineffective at preventing HIV.
Only one clinical trial, which took place in Thailand with results published in 2009, has been found to show modest effectiveness in preventing HIV infection. The efficacy of that vaccine, RV144, was about 30% (although the findings continue to be debated). For PrEPVacc to be considered a success, either of the two vaccines being tested will need to achieve an efficacy of at least 70%.
One vaccine combines pieces of synthetic HIV DNA with a protein base, while the other combines DNA, MVA (a weakened pox virus) and a protein base, like that used in RV144.
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