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The experience with soluble CD4 showed Ho that there were significant gaps in science's understanding of the life cycle of HIV. He decided to revisit his earlier Boston work on the first stages of infection. By hanging out in hospital emergency rooms and talking to colleagues, he and his team at UCLA identified four young homosexual men suffering from the flu-like symptoms of a primary HIV infection. Ho used a newly available tool of genetic engineering--the PCR test used most famously in the O.J. Simpson trial--to measure the amount of virus in the blood. Once again, he was astonished.
By this time, most researchers agreed that people in the later stages of AIDS had large quantities of HIV in their blood. But the PCR test showed that millions of viral particles were coursing through Ho's patients' blood in the earliest weeks of infection as well--as many as could be found in someone with a full-fledged case of AIDS. Within a few weeks, the viral load plunged to low and in some cases undetectable levels. The patients recovered and seemed healthy.
Ho wasn't the only scientist who had observed this. Another team, headed by George Shaw, had seen the same spike in HIV particles followed by a precipitous drop. The two researchers learned of each other's work and decided to co-publish their findings in a 1991 issue of the New England Journal of Medicine. It was the beginning of a friendly but no less keen competition between the scientists.
It was also the beginning of a new phase in Ho's career. Philanthropist Irene Diamond had decided to found an AIDS research center in New York City and had chosen Ho as its director. He was 37 years old. "I took a bit of flak because everybody said, 'He's so young, he's unknown.'" she recalls. "I said, 'I don't want a star, I want a wonderful scientist.'" For his part, Ho considered the benefits of having more lab space and secure financial backing. "It was still a risky venture," he remembers. "Marty Hirsch said, 'You're crazy. This is New York City. The politics will eat you up.'" But for Ho, the chance to do what he wanted, and to attract top-level scientists to join him, was too good to pass up.
Ho and Shaw had proved that there are high levels of virus in the first few weeks of infection. Ho and Schooley had already shown that there is a lot more virus in the end stages of AIDS than anyone had thought possible. The next question was obvious: What is going on during those middle years, when patients are still in relatively good health? Ho suspected that the answer could dramatically change the way doctors treated their HIV-positive patients.
All the blood tests indicated that the viral load was close to zero throughout the middle years, though it would gradually increase as time went by. Both Ho and Shaw realized, however, that zero doesn't always equal zero in the world of HIV. For one thing, the virus might be hiding out in the lymph nodes, where it could be producing thousands or even millions of copies of itself every day. As long as the immune system cleared those infectious particles as quickly as they formed, blood tests would show no change in viral load. "It's like a person running on a treadmill," Ho explains. It doesn't matter how fast they run. To an observer, they appear to be staying in place.