An innovative patient-specific immunotherapy offers a new and promising strategy for fighting HIV, making it possible for patients to suppress the virus even after stopping drug treatment.
Biopharmaceutical company Argos Therapeutics presented the results of clinical trials for the therapy, AGS-004, earlier this year at the Conference on Retroviruses and Opportunistic Infections in Boston. The company reports that some trial participants have gone months without medication and their virus is still undetectable.
AGS-004 immunizes the patient to HIV by inducing the immune system to generate anti-HIV memory T-cells to respond to the virus. Because memory T-cells can persist long-term, the immune system is able to hold off viral rebound for extended periods. The idea behind the pioneering treatment is to establish an immune response “that has some staying power, that can self-persist to hopefully have a longer clinical benefit,” says Charles Nicolette, Ph.D., Argos Therapeutics’ chief scientific officer and vice president of research and development.
The Argos research offered reason for optimism. During Phase IIa clinical trials, researchers stopped antiretroviral therapy in patients with HIV for 12 weeks. With the help of AGS-004, approximately 70 percent of those patients developed an immune response that allowed them to maintain undetectable viral loads for long periods of time.
Additionally, a separate study by David Margolis, MD, and his team at the University of North Carolina, focused on patients with acute HIV infection, produced even more promising results. When administered to six patients who had begun antiretroviral treatment within 45 days of primary HIV infection, AGS-004 was able to induce immune responses in every patient, one of whom maintained viral control while off treatment for almost nine months. These results indicate that the healthier the individual is from an immunological perspective, the more likely AGS-004 will generate the desired response against the virus.
Researchers say AGS-004 stands to be effective because, unlike other therapies, it is personalized. People with HIV can have wildly differing infections, they point out. “[HIV] persists so well and is so effective because of its high mutation frequency,” notes Nicolette. “It can continuously change, and the diversity of viral species that exists in a single patient who has been infected for a period of time is enormous.”
“We wanted to ask the question, If we matched immunotherapy to the patient’s own specific viral mutations, can we mediate some clinical benefit?” he continues.
The therapy involves taking a small sample of a patient’s blood plasma and dendritic cells—cells that are capable of activating T cells. The sample is used to isolate genetic material representing the patient’s infection, then program dendritic cells to target antigens, or antibody generators. These cells are then mixed with the plasma and injected into the patient, with the expectation that they will make T cells attack the patient’s particular version of the virus.
Argos is moving forward with more clinical trials. One scheduled for this fall will focus on young people with HIV who have been on antiretrovirals since birth. Another currently ongoing study aims to eradicate the virus in patients by using AGS-004 in conjunction with antilatent therapy, which targets HIV lying dormant in the body.
But is it a cure?
“Obviously that’s a very high bar,” Nicolette says. “But even a partial success in showing that we lower the number of latently infected cells in patients would be a step in a positive direction.”