New research co-led by Doherty Institute Director Professor Sharon Lewin has found that a drug used to treat cancer can also bring HIV out of hibernation, exposing the virus to the immune system and making it more susceptible to attack.
The ability of HIV to “hide” in cells, even in people receiving antiretroviral therapy and with undetectable amounts of virus in their blood, is one of the major barriers to finding a cure for the disease.
Although HIV patients treated with antiretroviral drugs have no chance of transmitting HIV and can lead normal, healthy lives, the virus is never completely cleared from their cells.
This is because an HIV reservoir “hides” in a state of hibernation in the cells of the immune system. To destroy the virus, these cells need the help of killer T cells. But because these T cells can’t detect and find hidden HIV, they can’t kill it.
In cancer patients, killer T cells become dysfunctional, leading them to express depletion proteins on their surface called PD1. Lewin’s previous research found that PD1 are the same depletion markers that allow HIV to hide in cells.
Pembrolizumab, an intravenously administered immunotherapy drug, blocks these markers of depletion in cancer patients, allowing killer T cells to regain their function and fight the cancer. The anti-PD1 drug has revolutionized treatments for various types of cancer, including melanoma.
One barrier in testing the treatment for HIV patients has been that pembrolizumab can cause significant side effects.
“Between 5% and 10% of people will experience an adverse event due to pembrolizumab,” Lewin said. “In a cancer setting, this is not a major concern as you have a life-threatening disease, but in the case of HIV, the situation is very different. People can now live normal, healthy lives with HIV, so any intervention for a cure must have very low toxicity.”
But Lewin and his team were able to test pembrolizumab against the virus by giving it to 32 people living with HIV who also have cancer. They found that the drug had anti-PD1 properties for HIV. Their discovery was published Thursday in the journal Science Translational Medicine.
Until now, there have only been individual case reports showing the effect of anti-PD1 because people with HIV who also need the treatment for their cancer are very rare. And while other treatments have been shown to reverse HIV latency, anti-PD1 has the additional potential to stimulate the immune response.
“So it’s like you have a two-in-one medicine,” Lewin said.
Lewin’s research has proven the concept that the drug can reverse latency in HIV patients, but whether anti-PD1 also stimulates the immune system enough to attack and destroy HIV will be the next part of his work.
“Can the effect of the immune system be further enhanced by combining anti-PD1 with other agents? [drugs] for even greater effect? And then the most important thing to look at now is, how do you dose anti-PD1 safely in people who have HIV but don’t have cancer?” Lewis said. “That is a study we are about to embark on.”
Stuart Turville, an associate professor and virologist in the immunovirology and pathogenesis program at the Kirby Institute at the University of New South Wales, said Lewin’s team was known for examining latency-reversing agents, “basically, compounds that could wake up the virus “.
“It’s normal for our immune system to be resting,” he said, “until our body sees something we need to respond to. HIV takes advantage of this. It enters resting cells and in doing so remains there for years.
“Importantly, in this study of HIV-positive cancer patients, they observed that the virus was awakened after administration of the PD1 inhibitor by using state-of-the-art molecular techniques developed to analyze the HIV reservoir with high sensitivity and in [a] granular level.”
He believes the study shows there may be “potential for this and similar treatments to develop a path toward a pragmatic cure for HIV.”
Lewin said that while existing HIV treatments were safe, effective and conducive to good health, working toward a cure was still important because treatment was lifelong and not everyone had access to it.
“Globally, 70% of people have access to treatment, and access to antiretroviral treatment for life is not guaranteed for everyone and is a real challenge for the world,” he said. “There are 1.8 million new HIV infections every year, so that group of people is only going to get bigger. That is why we need a cure as well as a treatment.
“I think anti-PD1 will ultimately be part of a multi-pronged intervention. But I think it’s very unlikely that a single drug or intervention will cure HIV.”
George is Digismak’s reported cum editor with 13 years of experience in Journalism