Durham-based Argos Therapeutics and UNC-Chapel Hill are embarking on a quest that has eluded medical science since the outbreak of the AIDS epidemic in the 1980s. The university on Wednesday was awarded $6.6 million in federal research grants to test experimental medications designed to eradicate the HIV virus that causes AIDS.
Argos, which is supplying experimental medication for the study, said Wednesday the grant from the National Institutes of Health will fund the first human clinical trial to test an emerging strategy scientists call “kick and kill” or alternately “shock and kill.” The approach, designed to purge HIV out of the human body, will be tested at UNC, home to the nation’s lead program funded by the NIH to find a permanent cure for AIDS.
“It actually is equipped to really do the dirty work and eliminate the infected cell by assassination,” Charles Nicolette, Argos’ chief scientific officer, said of the experimental approach.
The UNC and Argos scientists involved in the research plan to enroll 18 to 20 volunteers infected with HIV to participate in the 18-month study, which is expected to start within several months. The study protocols and ethical standards still require approval from the NIH and from UNC’s Institutional Review Board.
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The investigators are careful not to over-promise what they can deliver to research volunteers infected with HIV, and caution that finding a cure for AIDS will likely take a decade or two. Nicolette described the upcoming clinical trial as a proof-of-concept study that could lead to further developments in the scientific march towards a permanent cure.
“This is not really of any immediate benefit to any of these people,” said lead investigator David Margolis, a professor of medicine, microbiology and immunology, epidemiology at the UNC School of Medicine.
Argos is a 15-year-old company with 115 employees and no drugs on the market. It is developing a suite of personalized immunotherapies for cancer and infectious diseases.
Modern medicine has succeeded in suppressing the resilient HIV virus from replicating, but not in flushing it out of its human host. When attacked by drug cocktails, HIV goes underground and hides as long as the patient continues taking the medication.
Untreated, HIV destroys its host by disabling the immune system and exposing the victim to opportunistic infections. Without a cure, people infected with HIV have to take drugs for life to stay alive, but otherwise can lead healthy lives.
Only one person has been cured of HIV, but that was through a bone marrow transplant from a donor with a rare genetic mutation.
Argos’ experimental treatment, called AGS-004, is a personalized immunotherapy using DNA from the patient’s own particular virus to trigger an immune response against that virus. The therapy is personalized because HIV mutates so often that no two people have been colonized by an identical HIV strain, Nicolette said.
“You’re not just infected with a virus,” he said. “You’re infected with a whole swarm of quasi-species, mutated versions.”
The UNC clinical trial will combine Argos’s AGS-004 with a second therapy to make HIV-infected cells more visible to the immune system to maximize the immune system’s attack. UNC will contribute the agent, vorinostat, to lure the HIV out of hiding, and Argos will supply the weapon to destroy it.
UNC published the first research on exposing hidden HIV a decade ago, and the procedure “didn’t work so well,” Margolis said. Subsequent research, published in 2012 in the journal Nature, perfected the technique, he said.
“I believe this is the first study in the world that will get going that actually has the two parts working together,” he said. “The trick will be how they work together.”