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But what if you could avoid all those problems, Ho wondered. What if you didn't wait until the end stages of the disease but started combination therapy during the first few weeks of the infection, before too many billion viral particles had formed, before resistance became inevitable, before too many billion immune cells had died in the body's defense? Would you have tilted the odds enough in the immune system so that it could wipe out whatever stragglers might be left, wherever they were hiding?
To find out, Ho and one of his team, Dr. Martin Markowitz, recruited two dozen men in the earliest stages of infection and placed them on combination therapy. All the men appeared healthy before treatment. For them, ironically, the first signs of illness have been the side effects of the drugs they are taking, not the virus. Three have dropped out because they couldn't take the nausea and cramping.
Some of the men have been treated for more than a year. None of them show any trace of HIV in any of their blood. Ho has not forgotten, however, that zero does not always equal zero. He and Markowitz are looking for pockets of virus in the lymph tissue, the semen and the spinal fluid.
Ho believes that prospects for success are good. Assuming that nothing has been overlooked, combination therapy should burn the virus out of the body in two to three years, according to Perelson's latest mathematical models. Because treatment began so early, the men's immune systems should be able to replace any lost defensive cells. There is still a chance that bits of the virus, called proviral dna, are lodged in the chromosomes, beyond the reach of even the most powerful drugs. Ho has studied these vestigial snippets of genetic information and believes they are defective and cannot give rise to a new generation of HIV. Other scientists are not so sure. The only way to find out is to stop the medication and see if the virus comes back.
None of Ho's patients plan to take that step anytime soon. And he doesn't blame them. Just a few surviving viruses could manufacture enough copies to resaturate a body in a matter of days, forcing the patient to start the long treatment process all over again. But at least one of Ho's patients has agreed to stop taking his drugs in another year or two--after his doctors assure him that tests show no evidence of HIV in his lymph, semen, spinal fluid or elsewhere in his body. When he does, we will know, probably within a few weeks, whether the virus has returned or whether it is gone for good.
Even if the virus stages a comeback, that doesn't necessarily mean that combination therapy has totally failed. It may be that additional ingredients could eliminate the virus completely. Ho has already started using a combination of four drugs in another early-intervention trial. And he has access to new, experimental medications that can better penetrate the brain and perhaps the testes. These drugs may help patients in later stages of the disease whose infections have become resistant to current treatments.