The study included 41 participants across eleven sites across Canada, the United States and Australia. The subjects showed variable responses, but the virus was undetectable in a few of them two years after the therapy ended – even though the treatment had been cleared from their bodies for a very long time.
“I’ve been doing national and international clinical studies for seventeen years (and) this is the first time that it’s worked,” said the study’s principal investigator, Dr. Jean-Pierre Routy of the McGill University Health Center. And what’s encouraging is that it works even when the product is no longer there.”
The randomized, double-blind, placebo-controlled study evaluated the safety and tolerability of budigalimab, a monoclonal antibody targeting programmed cell death protein 1 (PD-1), in people living with HIV.
Simply put, PD-1 is a “brake” that stops the immune system from going into overdrive and starting to attack healthy cells. Cancer cells, for example, are able to express a protein that fools PD-1 and makes them appear to be healthy cells, making them immune to an immune response.
In this study, Dr. Routy and his colleagues used doses of budigalimab up to twenty times smaller than doses used in oncology to remove this barrier and allow the immune system to attack HIV with more power.
The study was conducted in two stages, with preliminary data generated in the first being used to determine the dosage used in the second. Resurgence of the virus was delayed in six of the eleven participants who received treatment in the second stage of the study. Two of them were able to remain without antiretroviral treatment for more than six months, without showing viral rebound.
“The beautiful thing is that it persisted even though the drug had disappeared,” said Dr. Routy, who is also the principal scientist in the Infectious Diseases and Immunity Program in Global Health at the MUHC Research Institute. So we probably improved, restored something. It’s very promising, but we need to go further.”
The researchers got a “dramatic” response in about a third of the participants, he added.
Those who presented the best response, explained Dr. Routy, were those who had not yet been too “damaged” by the disease, therefore those who had been ill for a shorter period of time.
“We are not creating new immunity, we are amplifying (existing) immunity,” he clarified. So if we take people who are treated in the first year, which is done in the majority of cases in Canada, we can have hope that we could live without HIV. But those who arrived very late, who took medication after six or eight years and who were starting to be weakened, honestly I think it’s not the best strategy.
The handful of patients who showed no trace of the disease two years after treatment ended returned to their usual treatment as a precaution, Dr. Routy said, but these participants perhaps “could have lasted longer, but the doctors were afraid.”
PD-1 inhibitors will not replace triple therapy in the treatment of HIV tomorrow morning, he warned, since we still need to learn how to use this new weapon in the right way, and especially in the right patients.
“We have to supervise it, we have to do it at the right time, because we don’t want to return to a hyperinflammatory state,” said Dr. Routy. If we put a vaccine or antibodies that are really specific for the virus, we could play in ranges that could be compared to triple therapy, but we are not there.”
For the moment, he added, this discovery at least allows HIV patients who must comply with triple therapy daily to hope for better days.
“It’s a ray of sunshine for them,” concluded Dr. Routy. It’s still a slightly different tone than saying “Ah yes, you have to take this medication (triple therapy) all your life”, which is terrible. I find that deeply discouraging, instead of telling them that we are going to take this medication until we get better or until we have strategies to repair immunity.”
The findings of this study were published by the journal Nature Medicine.
