Researchers Able To Lure Out, Kill Latent HIV in Mice, Study Says

Researchers at the University of California-Los Angeles have stimulated latent HIV reservoirs in mice and killed the virus with immunotoxins, according to a study published in the September issue of Immunity, the New York Times reports. HIV can "hibernate, virtually forever" in the cells of HIV-positive people who are taking antiretroviral drugs, according to the Times. Finding such latent reservoirs is difficult because HIV hides in the same memory T cells that act as triggers for the immune system; failing to locate the virus within such cells keeps HIV hidden but activating too many T cells can cause a serious immune reaction, like that of toxic shock syndrome, which could kill the patient, according to the Times. Drs. Jerome Zack and David Brooks and colleagues at UCLA used interleukin-7 and prostratin -- agents that activate viral expression -- to awaken HIV-infected T cells in mice. The chemicals caused the T cells to display some HIV proteins on their surfaces without causing the cells to divide or activate other T cells to begin an immune response. Once HIV-infected T cells were identified, a molecule-sized bacterial poison attached to an antibody locked onto the T cell and injected a toxin. Using this technique, the researchers were able to deplete 80% of the latent reservoir of HIV in the mice. However, killing only 80% of the latent virus is probably not sufficient enough to prevent HIV from reemerging, Zack said. Repeated tests in humans show that even if HIV is present in just one dormant T cell, the virus will reemerge if antiretroviral therapy is discontinued, according to the Times.

Better Model
Dr. Robert Gallo, director of the Institute of Human Virology at the University of Maryland, said that the mouse model in the UCLA study was "a very artificial system," adding, "If you had this in a monkey model with demonstrable safety data, that would merit highlighting it." Gallo said that if humans were given big enough doses of interleukin-7 and prostratin to identify HIV in their T cells, it could be "terribly dangerous." Zack said that he might test combinations of other drugs in order to identify HIV-infected T cells or conduct tests using the drugs in "pulses," the Times reports. In addition, Zack may test the use of immunotoxins in combination with antiretrovirals because immunotoxins are too poisonous to use alone against HIV, and, if successful, he will test the technique in monkeys and humans (McNeil, New York Times, 9/23).