Bristol-Myers Cancer Drug Opdivo Shows Surprising HIV ImpactBy and
HIV reservoirs drained in Paris patient treated with Opdivo
Single case result is ‘exciting’ but scientists urge caution
Bristol-Myers Squibb Co.’s blockbuster drug Opdivo had a stunning effect on a lung-cancer patient treated at a Paris hospital: it drained hard-to-reach reservoirs of his HIV infection, too.
The 51-year-old man, who was diagnosed with HIV in 1995, had a “drastic and sustained decrease” in the reservoir of cells where the virus hides to evade existing therapies, researchers wrote in a letter published Friday in the journal Annals of Oncology.
Scientists rarely promote results from a single case, but these findings could point to the goal that’s eluded AIDS researchers for more than three decades: an outright cure. The unexpected response to several months of Opdivo is the first report of a successful depletion of the HIV reservoirs and suggests the cancer drug may help eradicate HIV infected cells with a mechanism the researchers dubbed “shock and kill.”
“Although this is a single case study, it is an exciting result,” Fabrice André, the cancer journal’s editor-in-chief and a professor at Institut Gustave Roussy’s department of medical oncology in Villejuif, France, wrote in a statement. “Anti-HIV drugs usually stop virus replication but don’t cure the patients.”
The scientists urged caution about their findings. In a similar case they documented with Opdivo, and another they noted with Bristol-Meyers’ Yervoy, there was no decrease in HIV reservoirs.
The report is too preliminary to draw firm conclusions, according to HIV experts at Johns Hopkins University in Baltimore. The depletion of the reservoirs could have stemmed from something else, such as a low-level infection or other drug treatment.
“It is a single patient with a single observation,” said Janice Clements, director of the retrovirus laboratory in the Institute of Basic Biomedical Sciences. “Not very convincing or conclusive.”
HIV, once a death sentence, has become a manageable chronic condition with antiretroviral therapies that keep diseased cells from multiplying. But because some infected cells go into a resting state, in which they don’t produce new HIV, the medicines are powerless to flush them out. These so-called latent reservoirs can be found throughout the body, in the brain, bone marrow and lymph nodes.
When a patient stops treatment, the virus reemerges from these hiding places, generally within two weeks, said Andrew Badley, an infectious disease specialist and HIV researcher at the Mayo Clinic in Rochester, Minnesota. While the Paris patient’s HIV DNA level never went down to zero, the results are promising since the normally stable measure dropped dramatically in 120 days, he said.
Opdivo is part of a new generation of therapies that harness the body’s immune system to attack tumors. The drugs, known as checkpoint inhibitors, block a protein called PD-1 that prevents the immune system from recognizing and destroying malignant cells.
HIV is a disease of the immune system, and the researchers theorized that checkpoint inhibitors like Opdivo could have a similar impact on HIV-infected cells with high levels of PD-1, taking the brakes off the virus’ activity inside the reservoirs. Once the virus starts replicating again, it’s visible and vulnerable to HIV drugs and the body’s natural defenses.
Opdivo also may restore the function of other immune-system cells that have been exhausted during the fight against the virus, allowing them to resume killing HIV-producing cells, the researchers said.
“There is a lot of evidence that inhibiting these checkpoints could be a good thing for HIV therapy,” Badley, who wasn’t involved with the study, said in a telephone interview. “This paper suggests using a PD-1 inhibitor, with other treatments designed to eradicate HIV reservoirs, might contribute to a cure one day. But in and of itself, this won’t be a cure.”
The Paris patient, who was diagnosed with the most common form of lung cancer in 2015, was treated with Opdivo after he had relapsed following surgery and chemotherapy. His cancer is still progressing, albeit slowly.