New anti-cancer drugs can help kill HIV cells

Research into the potential of cancer drugs in clinical trials suggests they may be effective in treating latent HIV infection in patients receiving antiretroviral therapy (ART), which suppresses the virus.

Although antiretroviral therapy has helped to significantly reduce the global HIV mortality rate, the search for drugs to completely eliminate the disease continues.

A team of scientists from the SBP Institute for Medical Research (La Jolla, California) used anticancer drugs of the SMAC mimetics class (imitators of secondary mitochondrial activator of caspase - an endogenous protein that stimulates apoptosis of cancer cells) to suppress "sleeping" cells of the human immunodeficiency virus in the body of HIV-infected people undergoing treatment with antiretroviral drugs that only slow the progression of HIV infection.

Standard antiretroviral drugs work by stopping HIV cells from multiplying and giving the body's immune system the ability to prevent other infections. However, HIV has never been completely eradicated with ART. And the problem with treating HIV is that after you stop taking antiretroviral drugs, some of the dormant virus cells become active, causing a new active phase of the disease.

According to one of the leaders of the new study, Dr. Lars Pasche, scientists are looking for methods to cleanse the cells in which the immunodeficiency virus "slumbers." Specialists have dubbed this approach "shock-damaging," but so far there has been little success in its development. The drugs created to date - latency reversal agents (LRA) - do not produce the expected effect, and in some cases stimulate the immune system so much that it leads to the death of patients.

The results of a new study, published in the American scientific journal Cell Host & Microbe, say that scientists have established a link between increased HIV activity and the absence of the BIRC2 gene in patients, which codes for an endogenous inhibitor of programmed cell death (apoptosis) - the cIAP1 protein. Since anticancer SMAC mimetics block the BIRC2 gene, researchers are interested in the potential ability of these drugs to make the dormant virus "wake up." This would allow it to be identified and attacked by the immune system.

As scientists note, the immunodeficiency virus manages to hide from the immune system thanks to its “tightly wound” DNA. They suggested that SMAC mimetics could be combined with a drug from the histone deacetylase inhibitor class, Panobinostat, which works by unwinding this DNA.

The researchers tested the SMAC mimetic BOO-0637142 in combination with panobinostat on cells taken from HIV-infected patients undergoing ART. And the drug combination reawakened the HIV cells without activating the immune system. A trial with another anti-cancer SMAC mimetic, LCL161 (which is just entering clinical trials in oncologists), showed the same result.

Study co-author Dr. Samit Chanda notes that SMAC mimetics plus histone deacetylase inhibitors are a one-two punch against HIV, far more powerful than latency reversal agents (LRAs), suggesting that the research could be a step closer to solving the HIV latency problem.

The researchers' immediate plans include joining forces with a pharmaceutical company to conduct a relevant study of the safety and efficacy of the combination of these drugs in clinical models before testing them on patients.

In July of this year, Medical News Today reported on a study that found that HIV cells become active less frequently after antiretroviral therapy than previously thought: just once a week (the results of this study were published in the journal Pathogens).

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