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Not even the greatest marathoner could keep up that pace forever. If the virus reproduced very quickly, it would eventually exhaust the body's defenses. At least that's what Ho and Shaw thought. The trick to proving their idea was to find some way to suddenly stop the treadmill. If you did that to a jogger, he would lurch forward. Similarly, if you stopped HIV's cycle of reproduction in the blood, the immune system should suddenly rebound. By measuring that rebound, the scientists hoped to figure out just how rapidly the virus had been reproducing.
Great idea, in theory. There was just one problem: no one knew how to stop HIV that quickly. AZT wasn't powerful enough to do it. The pharmaceutical companies, however, had just started looking at a new class of substances, called protease inhibitors, that might fit the bill. As it turned out, it took several years of testing to come up with a formula for a protease inhibitor that was effective against HIV.
REINFORCEMENTS
The year was 1994, and the new drugs were finally producing good results in the test tube. They worked against laboratory strains of the virus; they worked against viral samples taken from patients. Where AZT merely slowed viral reproduction, the protease inhibitors shut it down almost completely. Unfortunately, almost wasn't good enough. It often took less than a month for a few viral particles to mutate into a strain that was resistant to protease inhibitors. The new drugs were starting to look like another failure.
But a few weeks was all that Ho and Shaw needed to conduct their rebound experiments. The two laboratories raced to find the answer.
Ho chose 20 volunteers whose T cells had dropped from a normal level of about 1,000 cells per ml of blood to fewer than 500. The newest PCR tests showed that the viral load of these patients was holding steady at about 100,000 copies per ml of blood. Ho started treating his subjects with one of the new protease inhibitors being developed by Abbott Laboratories. As expected, the amount of virus that could be measured in the patients' blood practically disappeared. The treadmill had been stopped. But no one was ready for what happened next.
Preliminary calculations indicated that the immune system was rebounding faster than anyone had thought possible. The results showed that in every day of every year, in every infected person, HIV produced not thousands, not millions, but billions of copies of itself. And every day the body launched billions of immune cells to counter the threat. The wonder was not that the immune system eventually crashed. Given such intense fighting and heavy casualties, the wonder was that it lasted so long. Ho and Shaw came up with the answer at the same time and published their results in back-to-back articles in a 1995 issue of Nature.
Suddenly the entire picture of AIDS had changed. As long as doctors thought that the virus was not very active through the early and middle years of infection, it made sense to conserve forces and delay treatment so they would be ready for the virus when it emerged from hibernation. Now it was becoming clear that the immune system needed all the help it could get right from the start.