May 3, 2002 -- A new study shows that HIV targets the same immune cells that are fighting to rid the body of the virus. This means that a promising AIDS treatment strategy may do more harm than good, researchers say -- but experts disagree.
The treatment strategy is called structured treatment interruptions or STI. Short-course STI strategies -- such as the week-on, week-off schedule being tested at the National Institutes of Health -- simply reduce the side effects of HIV drugs. The new findings -- published in the May 2 issue of Nature -- don't affect this concept.
Long-course strategies aim for something more. They seek to enlist the immune system in the fight against HIV. The risky strategy is to stop taking AIDS drugs and let the virus grow for a little while before restarting treatment. The idea is to stimulate the immune system against HIV. And that's the problem, according to Daniel C. Douek, MD, PhD, chief of human immunology at the National Institutes of Health's Vaccine Research Center.
Douek and co-workers have finally proven what researchers have long suspected -- that HIV infects and kills the very same immune cells that are trying to kill the virus. The AIDS virus likes to kill a kind of immune cell called the CD4 T cell. The new study shows that when this kind of cell targets HIV, it becomes a target itself.
"It's like during the day you set up your guns to fight the virus, and at night the virus sneaks in and takes all the guns," Douek tells WebMD. "The principle of this type of STI is to allow virus to come back, so theoretically you would be kind of self-vaccinating yourself. You may do that, but at the same time you will be allowing the virus to specifically target and infect the CD4 cells that fight the virus. You are robbing Peter to pay Paul."
Not so fast, says Luis J. Montaner, PhD, DVM, director of the HIV immunopathogenesis laboratory at Philadelphia's Wistar Institute. Montaner is studying a long-course form of STI in which patients take longer and longer drug holidays. Two years after beginning this study, he says, patients continue to do very well.
"This [Douek] paper to me is actually very encouraging about the potential of STI," Montaner tells WebMD. "The benefit may outweigh the cost you may have to pay. STI is still a potential treatment strategy. Our preliminary data suggests it can be beneficial. I am not at all deterred by this report."
Douek says he fears that if STI causes the body to make more HIV-fighting CD4 cells, it will "provide 'fuel' for viral spreading." Over the long term, he says, this will destroy the body's ability to fight off the AIDS virus.
Montaner, however, notes that the AIDS virus infects only a small proportion of HIV-fighting cells. This, he says, leaves the vast majority of the cells in position to fight the virus.
"If you follow their logic, they would say that because the infection is targeting the HIV specific response, over time you would erode that response to nothing," he says. "But people on STI are able to sustain this immune response. Their immune system is winning."
Montaner is quick to admit that his data are preliminary and that the long-term outcome of his STI strategy remains unknown. Douek is doubtful about whether long-course STI will ultimately prove to work.
"Having a lot of virus in your blood is a bad thing. It is that simple. Continued treatment is good," Douek says. "There was a lot of excitement and hope at the beginning, but the idea of self-immunization probably hasn't turned out to have worked."