To prolong the lives of AIDS patients, doctors rely on a battery of antiviral medicines with side effects that are often as damaging as those of chemotherapy. A long-sought alternative to antiviral medication is immunotherapy, in which a patient's own immune cells are removed, trained to fight the virus, and returned to the bloodstream to mount an attack. Reporting in the January issue of Nature Medicine, Wei Lu and colleagues at the University of Paris describe the first use of immunotherapy to successfully treat AIDS in monkeys.
The HIV virus evades the immune system by hiding inside the very cells that normally fight infection--the T cells--and causes AIDS by slowly killing them off, opening the door for opportunistic infections and cancers. Lu's team tried to counteract this Trojan horse attack in 14 macaque monkeys infected with SIV--a relative of HIV that causes AIDS in nonhuman primates--by culturing the monkeys' dendritic cells, cellular scouts that grab foreign agents from the bloodstream and present them to T cells to trigger immune responses. The researchers incubated dendritic cells with SIV treated with AT-2, a chemical that renders the virus harmless by permanently blocking viral replication, then they returned these SIV-trained cells to the monkeys' bloodstreams.
Lu says he'd hoped to simply find a measurable effect of this immunotherapy on SIV infection, but he was surprised by just how effective it was. Within 10 days, SIV viral load in infected monkeys was 1/50th of that of controls, and it remained at this low level for the remaining 34 weeks of the study. At best, says Lu, antiviral medications reduce viral load by less than fivefold and have to be taken daily for life. T cell counts in these monkeys also increased to healthy numbers.
“It will be very important to follow these animals for a longer period,” cautions Bruce Walker, a biologist at Harvard Medical School in Boston. One of the “major hurdles” to using immunotherapy to treat AIDS in humans, he says, is the ever-changing surface of the virus caused by its rapid mutation rate, which allows a few viral variants to slip past the immune system.