New research co-led by Doherty Institute Director Professor Sharon Lewin has found that a drug used to treat cancer can also wake HIV from hibernation, exposing the virus to the immune system and making it more likely to be attacked.

The ability of HIV to ‘hide’ in cells, even in people on antiretroviral therapy and with undetectable amounts of virus in their blood, is one of the main obstacles to finding a cure for the disease.

While HIV-positive patients on antiretroviral therapy have no chance of transmitting it and can lead normal, healthy lives, the virus is never fully cleared from their cells.

In effect, 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 cannot detect and find hidden HIV, they are unable to kill it.

In cancer patients, killer T cells become dysfunctional, causing them to express exhaustion proteins called PD1 on their surface. Previous research by Lewin found that PD1 are the same depletion markers that allow HIV to hide in cells.

Pembrolizumab, an immunotherapy drug given intravenously, blocks these markers of exhaustion in cancer patients, allowing killer T cells to regain function and fight the cancer. The anti-PD1 drug has revolutionized treatments for several cancers, including melanoma.

A hurdle in testing the treatment for HIV patients has been that pembrolizumab can cause significant side effects.

“Five to 10 percent of people will experience an adverse event from pembrolizumab,” Lewin said. “In a cancer setting, that’s not a major concern because 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.

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But Lewin and his team were able to test pembrolizumab against the virus by giving it to 32 people who are living with HIV but also have cancer. They found that the drug had anti-PD1 properties for HIV. Their finding was published Thursday in the journal Science Translational Medicine.

Until now, there have only been individual case reports to show the effect of anti-PD1 because people living 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 boost the immune response.

“So it’s like you have a two-in-one drug,” Lewin said.

Lewin’s research proved the concept that the drug can reverse latency in HIV patients, but whether anti-PD1 also stimulates the immune system enough to then attack and destroy HIV will be the next question. part of his job.

“Can you further enhance the effect of the immune system by putting anti-PD1 together with other agents [drugs] to achieve even a greater effect? And then the most important thing to look at now is how do you safely dose anti-PD1 in people with HIV who don’t have cancer? said Lewin. “This is a study that we are about to undertake.”

Stuart Turville, an associate professor and virologist in the Kirby Institute’s immunovirology and pathogenesis program at the University of NSW, said Lewin’s team was known for looking at latency-reversing agents – “essentially, compounds that could wake up the virus”.

“It’s normal for our immune system to rest,” he said, “by shutting down until our body sees something that we need to react to. HIV takes advantage of this. It enters resting cells and, in doing so, remains there for years.

“Importantly, in this study of cancer patients with HIV, they observed that the virus was awakened upon administration of the PD1 inhibitor using state-of-the-art molecular techniques developed to analyze the reservoir of HIV with high susceptibility and [a] granular level.

He believes the study shows there may be “potential for this treatment and others like it to develop a pathway to a pragmatic cure for HIV”.

Lewin said that although existing HIV treatments were safe, effective and lead 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 are 1.8 million new HIV infections each year, so this pool of people will only grow. This is why we need a remedy as well as a treatment.

“I think anti-PD1 will eventually be part of a multi-pronged intervention. But I think it’s highly unlikely that one drug or one intervention will cure HIV.