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Scientists shock dormant HIV out of hiding, leave AIDS-causing infection vulnerable to drugs

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Millions of Human Immuno-deficiency Virus (HIV) patients have been given a ray of hope after scientists moved one step closer to a cure. Currently, the Acquired Immune Deficiency Syndrome (AIDS)-causing virus can hide away at ‘undetectable’ levels in immune cells and avoid being killed off – meaning a patient can never be considered cured.

But researchers have successfully managed to force the virus to reactivate, leaving it vulnerable to the immune system and medication. The team used a drug called AZD5582 – which forces open cellular pathways in the immune system – to ‘shock and kill’ the hiding virus.

Researchers were worried the reactivated virus would trigger a slew of nasty side effects on the host. But to their surprise, the drug was a success and caused almost no negative health outcomes. The drug was only tested on animals.It worked even in the presence of antiretroviral drugs, which work by stopping the virus replicating in the body.

Patients are given the drugs to allow the immune system to repair itself and prevent further damage after infection.Researchers at the universities of North Carolina and Emory in Atlanta, United States (U.S.) – behind the latest studies – said the findings were “unprecedented”.

Medical advances over the past four decades mean patients with HIV can have unprotected sex without fear of passing it on.But the ultimate goal of discovering a cure for the virus, estimated to strike 37million people worldwide, has so far eluded scientists.

Even in patients deemed to have ‘undetectable’ count of the virus, there are still traces of HIV effectively sleeping inside their bodies.These are called latent viruses and don’t cause illness but cannot be destroyed by the immune system or medicines, making HIV impossible to get rid of.But when these latent viruses come to life and try to attack the body, they come out of hiding and the immune system and drugs can target them directly. Experts have for years been trying to find a way to activate the dormant virus from within immune cells and eliminate it, a tactic known as ‘shock and kill’.

But one obstacle has been finding a safe way to wake it up without overwhelming the immune system.University of Emory researchers looked at 12 monkeys infected with SIV, a close relative of HIV, and treated them with antiretroviral drugs. They used AZD5582 to force the HIV virus out of hiding. The drug appeared to be safe, with just one monkey experiencing a temporary fever and loss of appetite.

The next move will be to begin clinical trials in humans, researchers say. The team at North Carolina carried out the test on mice transplanted with human immune cells infected with HIV.Researchers stimulated the infected immune cells – called CD4+ T cells – while also depleting another kind of immune cell – called CD8+ T cells -, which normally keeps the virus in check. The combination saw the virus re-emerge, without harming the rodents, opening the door to potential new therapies to cure the sufferer.

Co-senior author on both papers Ann Chahroudi, an associate professor of pediatrics and director of the Center for Childhood Infections & Vaccines at Emory, said the studies described in the two papers take different approaches. She added: “AZD5582 was remarkable in its ability to reactivate latent SIV from resting CD4+ T cells, and to induce continued virus production in the blood when monkeys were still receiving daily antiretroviral therapy.

“The exciting thing about these papers being published together are the concordance of the results in two animal models with both approaches, and the opening up of new avenues for research towards the goal of an HIV cure.“HIV progressively damages crucial cells in the immune system, weakening the body’s ability to fight infections. “Left untreated, this leads to AIDS – the collective name for a series of deadly infections which the weakened immune system cannot tackle.”


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