Current anti-AIDS drugs are highly effective at making HIV undetectable and allowing people with the virus to live longer, healthier lives. The treatments, a class of medications called antiretroviral therapy, also greatly reduce the chance of transmission from person to person. But the medications do not actually rid the body of the virus.
HIV 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 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 scientists from UCLA, Stanford University and the National Institutes of Health may have developed a solution. 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 harboring HIV.
Scientists call the technique “kick and kill.”
Destroying the reservoir cells could rid some or all of the HIV virus from people who are infected. And although the scientists' approach has not yet been tested in humans, 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,” says Matthew Marsden, PhD, assistant professor of medicine in the Division of Hematology/Oncology. “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.”
To test the approach, the researchers gave antiretroviral drugs to mice that had been infected with HIV and then administered a synthetic compound called SUW133 to activate the mice's dormant HIV. Up to 25 percent 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 antiviral therapy, Dr. Marsden says.
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. In further studies, the scientists plan to learn how to make SUW133 less toxic and to evaluate its effectiveness in larger animals before it could be tested in humans.
“In Vivo Activation of Latent HIV with a Synthetic Bryostatin Analog Effects Both Latent Cell ‘Kick’ and ‘Kill’ in Strategy for Virus Eradication,” PLOS Pathogens, September 21, 2017