Researchers are taking a closer look at the cancer drug nivolumab which shows promise in targeting hidden “pools” of HIV-infected cells.
In a case first reported in the Annals of Oncology, the lung cancer drug nivolumab proved effective in helping the body’s immune system attack a type of HIV-infected cells that are normally immune to standard antiretroviral drugs.
This breakthrough discovery is based on the experience of one HIV positive patient in France who was being treated for advanced-stage, non-small cell cancer. The patient, who has been living with HIV since 1995, had already undergone chemotherapy and surgery for tumors diagnosed in 2015, before relapsing in 2016.
Doctors then decided to use nivolumab (Opdivo), a drug typically used to treat non-small cell lung cancer, advanced melanoma, and kidney cancer. Nivolumab is a checkpoint inhibitor. It can help the immune system find cancer cells by revealing tumors that use a specific protein that hides them from an immune system attack.
Surprisingly, the patient showed a significant decrease in HIV where it’s typically hidden in cells to evade standard treatment — with no side effects. However, while the results were promising, nivolumab still failed to completely eradicate the virus and affect a cure. Also, when the same drug was given to another patient, there was no improvement.
According to Dr. Stephen Parodi, chair of the board for the Council of Accountable Physician Practices (CAPP), “This report is a review of one patient’s experience. This study provides a basis for designing a trial to better understand whether immune modulating medications have a role in the treatment of HIV. We will need a larger number of patients and a formal trial to know whether this approach is both effective and safe.”
Dr. Jean-Philippe Spano, the study author and head of the medical oncology department at the Pitié-Salpétrière Hospital in Paris, insists in a press release that “It could have implications for HIV patients, both with and without cancer, as it can work on HIV reservoirs and tumor cells independently, the absence of side effects in this patient is also good news.”
According to the American Cancer Society, immunotherapy drugs like checkpoint inhibitors work by turning the immune system against a person’s own body, and they can cause side effects like fatigue, nausea, loss of appetite, skin rash, and even problems in major organs.
Marcella Flores, PhD, associate director, research at amfAR, says that, “Although immune checkpoint blockers (ICBs) have been used in cancer trials and have significant toxicities, we should draw from the cancer field, which has been using ICBs longer than the HIV field, to learn as much as we can about which patients may suffer from this treatment.”
And while “Immune checkpoint blockers have been used in HIV patients in the past with incremental success,” Flores insists that “Before starting a large randomized study, we should explore what makes this patient different than any other in the past.”
Dr. Amesh Adalja, senior scholar at the Johns Hopkins University Center for Health Security, says that, “The implication of the study is that it’s possible to awaken the latent HIV reservoir and prompt an immune response to diminish the size of this reservoir.”
Although he cautions that “The risk-benefit ratio may favor using the drug first only in HIV patients who have a cancer indication to assess how robust the response is, before using it on patients without cancers in which nivolumab is indicated.”
Although nivolumab didn’t fully cure HIV, “This case is unique and interesting and should be further explored despite the therapy having not eradicated the virus. The more we learn about why this particular patient responded so dramatically to this drug, the more the field gains in its fight toward a cure. This case is a hopeful mile marker in the way toward a cure,” said Flores.
Parodi adds, “This study is the first to demonstrate that the underlying reservoir of HIV virus hidden in immune fighting cells can potentially be made visible to the immune system. There is potential for a way to use an immune system [by] harnessing medical therapy to attack HIV hiding from the immune system.”
“The HIV reservoir is the single biggest hurdle to a cure for HIV. Scientists are taking a variety of approaches to attack the reservoir including ‘shock and kill,’ immunotherapy and ‘block and lock.’ Exciting work is also being done in approaches that bypass the immune system, such as gene therapy,” said Flores.
Adalja concludes, “While attacking dormant HIV has been an important research priority for several years, this study provides important proof-of-concept evidence that such an approach is possible. It will be important to follow this report up with additional studies in more patients, carefully weighing the risks and benefits of the treatment.”