New research co-led by the director of the Doherty Institute, Prof Sharon Lewin, has found a medicine used to treat cancer can also draw HIV out of hibernation, exposing the virus to the immune system and making it more susceptible to attack.
HIV’s ability to “hide” in cells, even in people on antiretroviral therapy and with undetectable amounts of the virus in their blood, is one of the significant barriers to finding a cure for the disease.
While HIV patients on antiretroviral drug treatments have no chance of passing it on and can live normal and healthy lives, the virus is never eliminated from their cells entirely.
This is because a HIV reservoir “hides” in a state of hibernation in immune system cells. To destroy the virus, these cells need assistance from killer T-cells. But because these T-cells cannot detect and find the hidden HIV, they are unable to kill it.
In cancer patients, killer T-cells become dysfunctional, leading them to express exhaustion proteins on their surface called PD1. Previous research by Lewin found PD1 are the same exhaustion markers which allow HIV to hide in cells.
Pembrolizumab, an immunotherapy drug administered intravenously, blocks these exhaustion markers in cancer patients, allowing the killer T-cells to regain function and fight the cancer. The anti-PD1 drug has revolutionised the treatments of several cancers, including melanoma.
A barrier in testing the treatment for HIV patients has been that pembrolizumab can lead to significant side-effects.
“Five to 10% of people will get an adverse event from pembrolizumab,” Lewin said. “In a cancer setting this isn’t a major concern as you have a life-threatening illness, but in HIV, the situation is very different. People can now live normal and healthy lives with HIV, so any intervention for a cure must have very low toxicity.”
But Lewin and her team were able to test pembrolizumab against the virus by administering it to 32 people living with HIV but who also have cancer. They found the drug did have anti-PD1 properties for HIV. Their discovery was published on Thursday in the journal Science Translational Medicine.
Until now, there had only been individual case reports to show 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 added potential to boost the immune response.
“So it’s like you have a two-in-one drug,” Lewin said.
Lewin’s research has proven the concept that the drug can reverse latency in HIV patients, but whether anti-PD1 also boosts the immune system enough to then attack and destroy HIV will form the next part of her work.
“Can you enhance the immune system effect further by putting anti-PD1 with other agents [drugs] to even get a bigger effect? And then the most important thing to examine now is, how can you dose anti-PD1 safely in people with HIV but who don’t have cancer?” Lewin said. “That’s a study that we are about to embark on.”
Stuart Turville, an associate professor and virologist with the Kirby Institute’s immunovirology and pathogenesis program at the University of NSW, said Lewin’s team was known for examining latency reversing agents – “basically, compounds that could wake the virus up”.
“It is normal for our immune system to be resting,” he said, “ticking over until our body sees something that we need to respond to. HIV takes advantage of this. It enters cells that rest and in doing so sits there for years.
“Importantly in this study of cancer patients with HIV, they observed the virus was woken up upon administration of the PD1 inhibitor by using cutting-edge molecular techniques developed to analyse the HIV reservoir at high sensitivity and at [a] granular level.”
He believes the study shows there may be “potential for this and other similar treatments to develop a pathway towards a pragmatic HIV cure”.
Lewin said while existing treatments for HIV were safe, effective, and led to good health, working towards 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 lifelong access to antiretroviral treatment is not guaranteed for everyone and is a real challenge for the world,” she said. “There’s 1.8 million new HIV infections every year so that pool of people is only going to get bigger. That’s why we need a cure as well as treatment.
“I think anti-PD1 will ultimately form part of a multi-pronged intervention. But I think it’s very unlikely a single drug or intervention is going to cure HIV.”
