New molecule could ‘kick and kill’ HIV

Scientists have developed a novel “kick and kill” technique against HIV that uses a molecule to awaken dormant virus cells and then knocks them out. Current anti-AIDS drugs are highly effective at making HIV undetectable and allowing people with the virus to live longer, healthier lives, said researchers at University of California, Los Angeles (UCLA) in the US. The treatments, a class of medications called antiretroviral therapy, also greatly reduce the chance of transmission from person to person.

However, the medications do not actually rid the body of the virus, which has the ability to elude medications by lying dormant in cells called CD4+ T cells, which signal another type of T cell, the CD8, to destroy HIV-infected cells. When a person with HIV stops treatment, the virus emerges and replicates in the body, weakening the immune system and raising the likelihood of opportunistic infections or cancers that can sicken or kill the patient.

Researchers have been looking for ways to eliminate the “reservoirs” where the virus hides, and they may have now developed a solution – a technique called “kick and kill”. Their approach involves sending an agent to “wake up” the dormant virus, which causes it to begin replicating so that either the immune system or the virus itself would kill the cell harbouring HIV. Destroying the reservoir cells could rid some or all of the HIV virus from people who are infected. Although the scientists’ approach has not been tested in humans yet, a synthetic molecule they developed has been effective at kicking and killing HIV in lab animals.

“The latent HIV reservoir is very stable and can reactivate virus replication if a patient stops taking antiretroviral drugs for any reason,” said Matthew Marsden, an assistant professor at UCLA. “Our study suggests that there may be means of activating latent virus in the body while the patient is on antiretroviral drugs to prevent the virus from spreading, and that this may eliminate at least some of the latent reservoir,” said Marsden, lead author of the study published in the journal PLOS Pathogens.

The researchers gave antiretroviral drugs to mice that had been infected with HIV, and then administered a synthetic compound called SUW133, which was developed at Stanford University in the US, to activate the mice’s dormant HIV. Up to 25 per cent of the previously dormant cells that began expressing HIV died within 24 hours of activation. With further development, the technique could lower the viral reservoir enough for people with HIV to be able to discontinue their anti-viral therapy, Marsden said.

SUW133 is based on bryostatin 1, a natural compound extracted from a marine animal called Bugula neritina. The research determined that the new compound is less toxic than the naturally occurring version.

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