New HIV drug that is like a "Swiss Army knife of immunotherapies"

By Dr. Ananya Mandal, MDApr 7 2019Reviewed by Kate Anderton, B.Sc. (Editor)

HIV is a tricky virus that causes a unique phenomenon where the virus hides within the immune cells of patients when they are on treatment with the antiretroviral therapy (ART) drugs. When they are off the drugs, the virus comes back. Researchers have now come up with a new drug that can push out the virus from its hiding and then kill is once and for all. The results of the preliminary study were published last week in the journal EBioMedicine.

The team from University of Pittsburgh that developed this immunotherapy said that this is the first step towards developing a vaccine against HIV. Early results of the drug in lab settings have shown promise they add. Human trials are still some time away, they agree. Researcher Robbie Mailliard said, “It's like the Swiss Army knife of immunotherapies.”

The team explains in the study how they engineered an immunotherapy and called it MDC1. The drug is capable of attacking both HIV and Cytomegalovirus (CMV). CMV is a common co-infection with HIV affecting 95 percent HIV positive individuals. Researcher Charles Rinaldo, a professor and chair of Pitt Public Health’s Department of Infectious Diseases and Microbiology, explained, “The immune system spends a lot of time keeping CMV in check; in some people, 1 one out of every 5 T cells are specific to that one virus. That got us thinking – maybe those cells that are specific to fighting CMV also make up a large part of the latent HIV reservoir. So we engineered our immunotherapy to not only target HIV, but to also activate CMV-specific T helper cells.”

Cytomegalovirus CMV in human cell. Image Credit: Kateryna Kon / Shutterstock

The team included blood samples of two dozen men from the Pitt’s Men’s study. This large study was again a part of the Multicenter AIDS Cohort Study (MACS). Researcher Jan Kristoff said, “The MACS participants were vital to the success of this study. You have to collect a lot of blood to find T cells latently infected with functional HIV in people on ART (anti retroviral treatment) — it could be as few as 1 out of every 10 million cells. So the men would sit for as long as four hours hooked up to a machine that processed their blood and came back multiple times to give more samples.”

They isolated dendritic cells that could kill the HIV virus. Robbie Mailliard explained that these cells, “hand off the ball and dictate the plays, telling other immune cells where to go and what to fight.” From these cells they created “antigen-presenting type 1-polarized, monocyte-derived dendritic cells,” or MDC1. Mailliard said, “Without adding any other drug or therapy, MDC1 were then able to recruit killer T cells to eliminate the virally infected cells. With just MDC1, we achieved both kick and kill – it’s like the Swiss Army knife of immunotherapies. To our knowledge, this is the first study to program dendritic cells to incorporate CMV to get the kick, and also to get the kill.”

The team found success with this approach and saw that MDC1 could coax the latent or hidden HIV virus in to the blood and then kill it effectively. This new therapy they add could be the “all in one” immunotherapy for HIV infected persons and could mean that patient no longer need to take life-long ART against HIV. At present they are seeking funding for large scale human trials with their approach.