Researchers use PD-1 checkpoint drug in pursuit of a promising curative approach to HIV
The big drug developers like Gilead and GlaxoSmithKline learned years ago how to keep a lid on HIV, but researchers remain challenged by their inability to root out the latent reservoirs of virus the hide in the cells.
But now investigators are pursuing a new research track that has just demonstrated its potential in a cancer patient in France.
Doctors there were treating a lung cancer patient with HIV with Bristol-Myers Squibb’s Opdivo and observed a “drastic and persistent decrease” in the virus hidden in cells. And there may be a very simple explanation.
Treating HIV patients with a PD-1 drug activates CD4 T cells, where the virus gravitates to hide. First generating a response by activating the virus, they then expose it to an amped up immune system in patients on powerful antivirals.
Doctors have been treating the 51-year-old patient — first diagnosed with HIV in 1995 — since late last year. Before treatment, the HIV was undetectable. But as treatment began the virus began to appear and then continued to rise for 45 days, at which point the immune response began to wipe out the exposed HIV.
“Increasingly, researchers have been looking into the use of certain drugs that appear to re-activate the latent HIV-infected cells,” Professor Jean-Philippe Spano, head of the medical oncology department at Pitie-Salpetriere Hospital AP-HP in Paris. “This could have the effect of making them visible to the immune system, which could then attack them. Drugs that inhibit immune check-points such as PD-1 are well known in the cancer field as being very efficient at restoring immune defences by removing the brake, enabling the immune cells to spring into action to reject the cancer cells. It was thought, but until now not demonstrated, that inhibitors of immune check-points could, in a similar way, wake up dormant HIV-infected cells and also the immune defences against the virus.”
There are some big caveats attached to this announcement. First, there was another HIV patient treated with nivo who didn’t respond. Second, they have to complete tox testing to see if non-cancer patients are threatened by checkpoint therapy. And they have to develop biomarkers for personalized treatment.