A trial of an experimental HIV vaccine has been abandoned after an interim analysis of the data suggested it was no more effective than placebo at preventing infections.
The vaccine regimen is based on a canarypox vector-based vaccine called ALVAC-HIV from Sanofi Pasteur and a two-component gp120 protein subunit vaccine supplied by GlaxoSmithKline.
The 5,400-subject HVTN 702 trial in South Africa was testing a vaccine developed by researchers at the US National Institute of Allergy and Infectious Diseases (NIAID) that was shown to have around 32% efficacy in an earlier study (RV144) in Thailand.
The latest update from the phase 2b/3 trial – which started in 2016 and is also known as Uhambo – found no evidence that it protected against HIV transmission, ending the development of the only vaccine regimen ever to show evidence of protection from HIV in a large-scale clinical trial.
The tendency of the virus to mutate means that conventional approaches to vaccine design have largely been ineffective, with at least four prior vaccine candidates also failing in trials.
Attention will now have to turn to earlier-stage candidates, such as a mosaic adenovirus serotype 26 based HIV shot developed by Johnson & Johnson which generated encouraging results in healthy volunteers and started a phase 3 trial called Mosaico last year.
A look at the data from HVTN 702 last week revealed 129 infections among recipients of the vaccine recipients compared to 123 in subjects given the placebo shot, and the trial’s data and safety monitoring board concluded that no more doses should be given.
The researchers altered the make-up of the vaccine compared to the one used in the Thai study to try to improve its efficacy, but to no avail. They targeted the subtype of HIV predominant in South Africa, increased the number of injections given, and added an immune-stimulating adjuvant (MF59) – also supplied by GSK – to the formulation.
“An HIV vaccine is essential to end the global pandemic, and we hoped this vaccine candidate would work. Regrettably, it does not,” commented NIAID director Anthony Fauci.
“Research continues on other approaches to a safe and effective HIV vaccine, which I still believe can be achieved,” he added.
Even a modestly effective vaccine could have an impact on the HIV epidemic in countries where the burden of the virus is high, particularly if used as a tool alongside current prevention and treatment strategies.