Could Keytruda Help Eliminate HIV?

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A widely used cancer drug that works on the immune system may push the HIV virus out of hiding possibly be attacked and eliminated, according to a new study.

Sharon Lewin

Sharon Lewin

Infectious diseases physician Sharon Lewin, director of the Peter Doherty Institute for Infection and Immunity and professor of medicine at the University of Melbourne, led the study, which examined how Keytruda (pembrolizumab) may reverse HIV latency. The results were published in Science Translational Medicine.

Keytruda is a monoclonal antibody that blocks programmed death-1(PD-1) receptors on the surface of T cells. By doing so, the agent makes cancer cells more recognizable to T cells. That recognition recruits an immunological response to the cancer, so the body’s own immune system goes into action against the cancer, killing off cancerous cells and limiting their growth.

Lewin explains that HIV “hides” inside long-lived T cells. This has been a major barrier to developing a permanent cure for HIV because the virus is never eradicated fully with antiretroviral therapies but continues to be present in the body within these latent reservoirs. And, more particularly, in people living with HIV who are taking antiretroviral therapy, the virus favors T cells expressing PD-1 receptors as a hiding place.

“We were keen to see if blocking PD-1 with the Keytruda, impacted HIV,” Lewin says. “We did the study in people living with HIV on antiviral treatment who had cancer. They needed Keytruda for their cancer. Because we know that PD-1 can also silence HIV, we asked if blocking PD-1 could essentially lure HIV from its hiding place.” The study included 32 people.

“PD-1 puts the brakes on the immune system and also puts the brakes on HIV,” she says. “We saw that anti-PD-1 reversed that process and allowed HIV to reactivate. Anti-PD1had an impact on HIV and did push it out of hiding. However, anti-PD1 alone didn’t reduce the total pool of infected cells that persist in people on antivirals.”

Lewin and her colleagues reported that after the first infusion of anti-PD-1, they saw a 1.32-fold increase in unspliced HIV RNA and a 1.61-fold increase in unspliced RNA-DNA ratio in CD4+ T cells and a 1.65-fold increase in plasma HIV RNA. “These data are consistent withanti–PD-1 being able to reverse HIV latency in vivo and support the rationale for combining anti–PD-1 with other interventions to reduce the HIV reservoir,” they wrote in the abstract for the study.

They also reported that repeat doses of anti-PD1 made it easier to activate the virus.

“The next step is to find the lowest safest dose of anti-PD1 (treatments) in people living with HIV on ART who are otherwise healthy,” Lewin says.

The results are very promising, Lewin adds: “Anti-PD1 (treatment) on its own doesn’t cure HIV, but together with other drugs, it may well have an important role.”

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