Scientists Identify Potential Drug to Block AIDS

Scientists may have just identified a potential drug to block AIDS. They've found the precise chain of molecular events in the human body that drives the death of most of the immune system's CD4 T cells as an HIV infection leads to AIDS. They've also found an existing anti-inflammatory drug that blocks the death of these cells, which could prevent HIV-infected people from developing AIDS and related conditions in the future.

In this case, the researchers found that during an HIV infection, a protein known as IFI16 senses fragments of HIV DNA in abortively infected immune cells. This triggers the activation of the human enzyme caspase-1 and leads to pyroptosis, a fiery and highly inflammatory form of cell death. This repetitive cycle of abortive infection, cell death, inflammation and recruitment of addition CD4 T cells to the infection "hot zone" ultimately destroys the immune system and causes AIDS.

"Gladstone has made two important discoveries, first by showing how the body's own immune response to HIV causes CD4 T cell death via a pathway triggering inflammation, and secondly by identifying the host DNA sensor that detects the viral DNA and triggers this death response," said Robert F. Siliciano, one of the researchers, in a news release. "This one-two punch of discoveries underscores the critical value of basic science--by uncovering the major cause of CD4 T cell depletion in AIDS, Dr. Greene's lab has been able to identify a potential new therapy for blocking the disease's progression and improving on current antiretroviral medications."

Currently, the researchers plan to conduct a Phase 2 trial, which will test an existing anti-inflammatory's ability to block inflammation and pyroptosis in HIV-infected people. This trial promises to validate a variety of expected advantages to this therapy. For example, by targeting the human body, or host, instead of the virus, the drug is likely to avoid the rapid emergence of drug resistance that often plagues the use of ARVs.

"This has been an absolutely fascinating voyage of discovery," said Warner C. Greene, one of the researchers, in a news release. "Every time we turned over an 'experimental rock' in the studies, a new surprise jumped out."

The findings are published in two papers, one in Nature and the other in Science.