New drug candidate reawakens sleeping HIV in hopes of functional cure

June 23, 2020

LA JOLLA, CALIF. - June 23, 2020 - Scientists at Cell Reports Medicine, aims to create a functional HIV cure by activating and then eliminating all pockets of dormant HIV--an approach called "shock and kill."

"What scientists have found with other 'shock' approaches is that they can be too hot and overactivate the immune system, or too cold and don't wake up the virus," says

Antiretroviral therapy (ART) has increased the life expectancy of people with HIV by decades--with many individuals now living as long as the general population. However, because HIV is able to hide in reservoirs in the body, infected individuals never fully clear the disease, and ART must be taken every day for the rest of an individual's life to keep the virus inactive. Like other chronic treatments,

Waking up sleeping HIV

This research builds upon the scientists'

In this study, the researchers administered Ciapavir to mice with a human immune system and were infected with HIV. The treatment significantly increased levels of HIV in the blood and bone marrow--indicating that the latent virus was activated. Importantly, immune activation was minimal. Overactivation of the immune system can be deadly and has historically been a problem with the "shock and kill" approach.

"Ciapavir is the first Smac mimetic specifically optimized for an HIV cure, so it is significantly more potent for HIV than other molecules in this class," says

The Goldilocks approach

Ciapavir is a small molecule that awakens dormant HIV by activating non-canonical NF-κB signaling in CD4+ T cells, the target of HIV. This lesser-used pathway only activates a subset of the immune system--which is the key to the drug's gentle approach.

"Non-canonical NF-κB signaling is part of the immune system's 'plan B' response to pathogens," explains

Ciapavir will next undergo further evaluation in nonhuman primates, as well as additional toxicology studies to ensure that the drug is ready for testing in humans. "Early shock and kill attempts to cure HIV used repurposed drugs and did not achieve their goal of reactivating latent HIV to useful levels," says

More than 37.9 million people around the world are living with HIV, according to the World Health Organization, including 1.1 million people in the U.S. The virus infects the CD4+ T cells of the immune system. As the infection progresses, the immune system is destroyed, which makes people more vulnerable to other infections and diseases. Without medicine, people with AIDS--or late-stage HIV--typically survive about three years.

The study's DOI is 10.1016/j.xcrm.2020.100037.

Research reported in this press release was supported by the National Institutes of Health (P30AI036214, R01AI124843, R01CA195227, P30CA030199) and the James B. Pendleton Charitable Trust.

The co-senior authors of the study are Cosford, Jerome Zack of UCLA, and Chanda, who is also the corresponding author. Additional study authors include Matthew Marsden of UCLA and Peter Teriete of Sanford Burnham Prebys, who contributed equally to the study; Alex Portillo, Dominik Heimann and Maria Celeridad of Sanford Burnham Prebys; Jocelyn Kim, Mohamed Soliman, Melanie Dimapasoc and Camille Carmona of UCLA; and Adam Spivak and Vicente Planelles of the University of Utah School of Medicine.
About Sanford Burnham Prebys Medical Research Institute

Sanford Burnham Prebys is a preeminent, independent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discoveries to profoundly impact human health. For more than 40 years, our research has produced breakthroughs in cancer, neuroscience, immunology and children's diseases, and is anchored by our NCI-designated Cancer Center and advanced drug discovery capabilities. For more information, visit us at

Sanford Burnham Prebys Medical Discovery Institute

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