Gilead Sciences – already a giant in HIV therapy – has teamed up with Spanish biotech Aelix Therapeutics to try to develop a treatment regimen that would go beyond controlling the virus and provide an effective cure for the infection.
The plan is to combine Gilead’s experimental toll-like receptor 7 agonist vesatolimod (GS-9620) – in clinical trials for HIV and hepatitis B – with a vaccine developed by Aelix that has been developed from people who seem to have an innate resistance to HIV.
The vaccine – called HTI – is an immunogen that is delivered into the body using viral vectors and aims to “re-educate” the immune system of patients so that they can control their HIV infection without antiretroviral therapy (ART), and is currently in early clinical development.
The partners intend to use vesatolimod to activate expression of HIV in the body, including in reservoirs such as lymph and other tissues where it lies dormant and safe from current drug therapies, in order to enhance the HTI vaccine-induced immune response. As HTI itself is designed to refocus the immune response to vulnerable areas such as reservoirs, the hope is that giving both approaches simultaneously will be a ‘double-whammy’ that could eradicate HIV from the body.
Earlier this year, Gilead reported a preclinical study in non-human primates that showed it took months for viral levels to rebound after treatment with vesatolimod and an HIV-neutralising antibody, while in some cases the infected animals showed a rebound but began re-suppressing HIV without ART.
Gilead is planning human trials of vesatolimod with an improved neutralising antibody candidate from its own pipeline, but the Aelix collaboration adds another string to its HIV eradication bow.
The proposed Spanish trial will enrol 90 patients who have started ART during early HIV infection and have HIV levels below the limits of detection, and is due to get started early next year. As with the preclinical trial, the intention is to dose with vesatolimod and HTI and then withdraw ART to see if the vaccine-drug combination can keep HIV levels under control.
Other groups are also working on eradication strategies, including an academic consortium led by Imperial College London, the University of Oxford, MRC Clinical Trials Unit at UCL, and the University of Cambridge. They conducted a trial of a similar approach – known as ‘kick and kill’ – combining vaccines with ART and a drug (vorinostat) to activate latent HIV, but yielded disappointing results.
“We found that all the separate parts of the kick and kill approach worked as expected and were safe,” said lead investigator Sarah Fidler of Imperial when the results were announced.
“The vaccine worked on the immune system, the kick drug behaved as we expected it to, and the ART worked in suppressing viral load in the body, but the study has shown that this particular set of treatments together didn’t add up to a potential cure for HIV, based on what we’ve seen so far.”
There’s no denying that eradication will be a tough nut to crack, as earlier efforts to use high-dose, phased ART to achieve a cure have also resulted in failure. And it’s a bold stratagem by Gilead, which generated $14bn in revenue from its ART drugs last year.