New treatment may flush HIV reservoir
BY Advocate.com Editors
September 18 2003 12:00 AM ET
A two-step approach against HIV involving first flushing the virus out of hiding then killing it with a toxic antibody may offer the first hope for controlling a lifelong AIDS infection, U.S. researchers reported on Tuesday. The technique to locate and kill dormant HIV-infected immune system cells works in mice and is ready to test in monkeys, the team at the University of California, Los Angeles, said. The process wouldn't be a cure, but could allow people to take years or even decades off of the powerful drug cocktails that can keep the virus at bay, but which cause serious side-effects from diarrhea to heart disease.
Writing in the September issue of the journal Immunity, lead researcher Jerome Zack and colleagues said they had devised a two-step system for first partially activating the cells the virus hides in, then killing the cells before the virus can escape. The cells they targeted are called resting T cells. When these cells are dormant, HIV drugs cannot find them and work against the virus hiding inside. "About one in a million T cells holds latent HIV that the antiretroviral drugs can't touch," said Zack. "In order to make it visible so you can attack it, you have to activate it." Attempts to activate these cells have failed in the past because fully activating all of a patient's T cells can create potentially deadly illness.
Zack's team used two compounds to only partially activate the T cells. One, interleukin-7, is a naturally occurring compound. The other, called prostratin, comes from a tree native to the Pacific island of Samoa. "They hit a specific activation pathway but don't fully turn on cells," Zack said. At that point they introduce an antibody that specifically targets HIV-infected cells that is spliced to a piece of diphtheria toxin. "Because the antibody is linked to a toxin molecule, it pops into the cell," Zack said. "The toxin kills the cell before lots of viruses are made." The approach worked in mice, clearing 70% to 80% of the reservoir of latent T-cells without mistakenly attacking any healthy T cells.
Zack envisions that the procedure would be used along with intermittent anti-HIV drug therapy to keep HIV from spreading in the body. Even then, he does not think it would offer a complete cure, but patients may be able to safely stop anti-HIV medications for years or even decades at a time once they achieve an undetectable level of virus in their bloodstream and then flush out the remaining HIV reservoir.