Cancer drug can expel dormant HIV from cells, study says

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The use of a drug indicated for cancer treatment has succeeded in expelling the dormant HIV virus from the cells of patients living with the pathogen.

The immunotherapy, called pembrolizumab, was successful in reversing the latency process of HIV in the cells of people with cancer who use antiretroviral cocktails and have a controlled viral load — that is, below the levels that can lead to the development of AIDS.

With the expulsion of the HIV virus in the cytoplasm, the defense cells were able to identify the latent virus and act on their cell death. The research is a step forward in the search for drugs capable of attacking cells infected by the virus in the body, one of the main challenges for the creation of a vaccine against AIDS.

The study was published in the specialized journal Science Translational Medicine on the 26th and included researchers from the United States, Canada and Australia.

To identify the action of the drug, the clinical trial included 32 volunteers, of which 29 (91%) had an undetectable viral load and only three (9%) had a viral level above the detection limit.

The drug acts on the release of anti-PD-1 molecules, an acronym for cell death programmer protein 1. This protein inhibits the action of defense T cells (such as CD4+ and CD8+, responsible for attacking pathogens and tumor cells), capable of identifying the invading virus.

Some T cells are long-lived and “keep” the HIV virus for years. Therefore, by binding to these molecules, the monoclonal antibody can help the body identify infected cells and attack them.

Each of the volunteers received a course of therapy and was evaluated every three weeks to determine the amount of T cells and HIV genetic material after treatment.

After eight days of the first cycle, the amount of viral RNA fragments detected increased 1.32 times, that is, the drug was successful in “expelling” the dormant virus from the cells. This number reached 1.6 times greater from the 22nd day, when the second cycle began.

Furthermore, after six cycles, or 126 days, the amount of T cells with detectable virus increased 1.44-fold, suggesting that the treatment was successful in reversing the inhibition of defense cells and making cells with dormant virus “visible”.

The study, however, concludes that trials with a larger number of individuals are still needed to determine what would be the ideal dose of pembrolizumab to reverse the dormancy of the virus and at the same time limit the side effects of the immunotherapy.

Sharon Lewin, director of the Peter Doherty Institute of Infectious Diseases and Immunology and a professor of medicine at the University of Melbourne and senior author of the research, says the possible toxicity of treatments to eliminate HIV from the body remains the main focus of the group’s investigation.

“We remain vigilant and alert with any toxicity that interventions for a possible ‘cure’ of HIV can cause in people who are undetectable for HIV, because the quality of life and expectation of these people is very high today,” he says.

“So the next step is to determine a reduced dose of anti-PD-1 that can be used to achieve the same effect on the virus, not just on T cells.”

The discovery of the mechanism, however, does not represent a possible target for the development of an HIV vaccine, because the anti-PD-1 antibody does not yet have a well-defined role in the initial immune response. Some animal models have shown that this may be one way, but larger human studies are still needed.

Research into the treatment and possible cure of HIV, however, has advanced a lot in recent years, especially with the advent of mRNA technology, such as that used in vaccines against Covid-19.

According to Lewin, a new generation of drugs to expel HIV from cells may even benefit from state-of-the-art gene therapy or mRNA vaccines.

“There is also huge interest in using these drugs [do estudo] in combination with others. In the end, we don’t believe that this strategy alone will help achieve a ‘cure’ for HIV,” she says.

“Drugs that eliminate the virus from the body need to be combined with interventions that specifically kill the infected cells. This combination of methods against HIV is currently being investigated in other animal models”, he adds.

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