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But where would that help come from? Boston's Martin Hirsch and other virologists had already started looking to cancer research for inspiration. Oncologists have learned that it is often better to combine the firepower of several different chemotherapeutic drugs than to rely on any single medication to destroy cancer cells. Too often, they have found, the one-drug approach allows a few malignant cells to survive and blossom into an even more lethal tumor. The AIDS researchers faced a similar problem with HIV. Whenever they prescribed a single drug, such as AZT, for their patients, a few viral particles would survive and give rise to drug-resistant HIV.
Now that the protease inhibitors had become available, doctors were eager to combine them with the old standby AZT and a third drug called 3TC. A couple of mathematical models--created by one of Ho's collaborators, Alan Perelson of the Los Alamos National Laboratory--suggested that HIV would have a hard time simultaneously undergoing the minimum three mutations necessary to resist combination therapy. He placed the odds at 10 million to 1. It was at least worth a try.
HOPE AT LAST
For once in the history of HIV, a strategy that ought to work seemed in fact to succeed. Within weeks of starting combination therapy, 7 out of 10 men and women with AIDS begin to get better. Blood tests show that in many of them, the viral load has dropped below detectable levels. Relieved of the burden of fighting HIV, their long-suffering immune systems can finally tackle the deadly fungal and bacterial infections that have taken hold in their lungs, intestines and brains. Fevers break; lesions disappear; energy returns.
With the virus under control in at least some AIDS patients, doctors are considering how to rebuild their battered immune systems. After a decade of fighting HIV, many of the body's defensive reserves have been thoroughly depleted and cannot be regenerated from within. Researchers plan to grow replacement cells in the laboratory for transplant into recovering patients. Before the advent of combination therapy, no one would have considered such a rescue effort because the unchecked virus would have rapidly destroyed the new implants.
It all sounds so hopeful. Why don't scientists say at the very least that they're close to the cure? For the same reason that Ho did not promise the crowd in Vancouver that he could eliminate HIV from people in the later stages of the infection. Researchers know that after years of infection, there isn't a hiding place in the body that the virus hasn't penetrated. A cure must do much more than clear HIV from the bloodstream. It must remove the virus from the lymph nodes, the brain, the spinal fluid, the male's testes and everywhere else it may be hiding. Today's combination therapies work in the blood, but they don't reach into the brain or the testes very well.
Chances are that people in the later stages of the disease will have to stay on combination therapy the rest of their lives--assuming they can tolerate the often excruciating side effects, which range from diarrhea and fatigue to spasms, kidney stones and liver damage. They also have to bear in mind that they are probably still infectious and that eventually--perhaps in a few years, perhaps longer--their immune systems will probably once again collapse.