When doctors in Paris treated an HIV-infected lung cancer patient with Bristol-Myers Squibb’s immuno-oncology drug Opdivo (nivolumab), they were stunned to discover a huge decrease in the patient’s viral “reservoirs”—hideaways in the body that allow HIV to escape from antiretroviral treatments.
The discovery, made at Pitie-Salpetriere Hospital AP-HP and reported in a letter to the journal Annals of Oncology, could lead to a new method for dealing with viral reservoirs, which have proven to be one of the biggest hurdles to developing HIV cures and vaccines. These reservoirs contain latent HIV-infected cells that can reawaken at any time, making it impossible to eradicate the virus for good.
The French researchers say they are planning a clinical trial of Opdivo in 50 patients with HIV, primarily with the goal of determining whether there are any toxicities associated with the drug. They had previously published details of another patient they had treated with the drug who showed no decrease in HIV reservoirs, so they needed to expand the sample size.
A spokesperson for BMS declined to comment because the company did not sponsor the study. The company does say on its website that Opdivo is in early-stage research for “immunoscience,” though it doesn’t list HIV as one of its research priorities.
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The Pitie-Salpetriere oncologists say it makes sense that Opdivo would have a positive effect on HIV reservoirs. The drug is a “checkpoint” inhibitor that blocks PD-1, an immune modulator that normally prevents the immune system from recognizing and eradicating cancer. HIV infects white blood cells known as CD4 T cells.
In those CD4 T cells, PD-1 has two functions when it comes to HIV: It blocks the reactivation of latent cells, and it prevents the cells from fighting the virus. So the hypothesis is that PD-1 blockers like Opdivo may work in HIV by waking up the latent infected cells, which would then make them more visible—and vulnerable—to the immune system.
After they gave Opdivo to the patient, the French oncologists observed an increase in another type of T cell, CD8, after which reservoirs of HIV-infected cells began to steadily fall, they said in a press release.
"In this patient we observed, as expected, both a re-activation of HIV and an increase in CD8 T cell responses against HIV, which resulted in the drastic decrease in the HIV reservoir, thus leading to a sustained reduction of the HIV reservoirs,” said Jean-Philippe Spano, head of the medical oncology department at Pitie-Salpetriere, in the release. The discovery, he added, “could have implications for HIV patients, both with and without cancer, as it can work on HIV reservoirs and [tumor] cells independently."
Several approaches for shrinking HIV reservoirs are being studied at labs around the world. And this past April, one team at the University of North Carolina announced they have found a new type of reservoir that protects the virus in macrophages, which are white blood cells that reside in the brain, liver and other tissues.
In addition to assessing side effects of Opdivo in HIV-infected patients, the French scientists plan to search for biomarkers during the upcoming trial that will help predict who might respond best to anti-PD-1 therapies. As for the patient described in the Annals of Oncology report, he will continue to receive the drug. His doctors report that his cancer is slowly progressing but that he “doesn't show any signs of disease,” according to the statement.