Researchers at the Nuffield Department of Medicine at the University of Oxford are leading a new clinical trial investigating whether immune-based interventions can enable longer-term immune control of HIV after stopping antiretroviral therapy (ART).
The Oxford-led AbVax trial, funded by the Medical Research Council, is designed to test a central scientific idea: that the immune system can be encouraged to better recognise and control HIV through a combination of broadly neutralising antibodies (bNAbs, provided by Gilead Sciences, Inc.), therapeutic vaccination and carefully monitored treatment interruption. The study focuses on understanding a proposed ‘vaccinal effect’, in which antibodies not only neutralise the virus but also help stimulate longer-lasting protective immune responses.
“Over the past three decades, antiretroviral therapy has transformed HIV from a fatal infection into a highly manageable long-term condition,” said Dr Paola Cicconi, Chief Investigator at the Jenner Institute, Nuffield Department of Medicine. “That progress has been extraordinary, but it should not mark the end of scientific ambition. If we are serious about improving long-term outcomes for people living with HIV, we also need to ask whether the immune system itself can be trained to play a more active role in controlling the virus.”
“This study is designed to tease apart which immune responses actually contribute to controlling HIV, and how they might be strengthened,” adds Professor John Frater, Senior Investigator from the Nuffield Department of Medicine. A central component of the trial is the use of bNAbs, which target conserved regions of the HIV virus and can act against many viral strains. Previous studies suggest that bNAbs can suppress HIV for extended periods and, in some individuals, delay viral rebound after treatment is stopped. AbVax explores whether this immune control can be strengthened by combining antibodies with therapeutic vaccination. The trial therefore incorporates three HIV vaccines developed by Professor Tomáš Hanke at the Jenner Institute, University of Oxford, which are designed to refocus the immune responses on the most vulnerable parts of HIV.
The trial will recruit 53 people living with HIV across three sites in Oxford and London (Oxford University in collaboration with OUH NHS Foundation Trust, Imperial College Healthcare NHS Trust and Guy’s and St Thomas’s NHS Trust). Participants will receive study interventions before undergoing a closely monitored pause in ART, allowing researchers to assess how long HIV remains suppressed without medication, whether the immune responses can control the rebounding HIV, and to analyse immune responses linked to viral control.
Although treatment has advanced dramatically, HIV continues to affect around 40 million people worldwide, with new infections and HIV-related deaths still occurring each year. These realities underline why research must continue to push beyond effective suppression towards approaches that further improve health and quality of life for people living with HIV.
AbVax is now open to recruitment at all three sites; further information can be found at www.abvaxstudy.org.