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But there the understanding runs out. Why does HIV lie dormant in human cells, usually for years, before producing a full-blown case of AIDS? What triggers the deadly phase of the infection? How does the virus go about destroying the immune system? Even at the height of the disease, HIV particles are found in no more than 1 in 100 CD4 T-cells. And yet the cells that do not harbor the virus die off almost as fast as those that do. Some researchers think that HIV must somehow provoke immune-system cells to destroy themselves.
One prominent theory is that the virus needs an assistant assailant -- a "co-factor," in scientific jargon. But the search for co-factors has been inconclusive. Although the presence of genital sores from syphilis or other ) venereal diseases makes transmission of the AIDS virus easier, neither the sores nor the microbes that cause them are necessary for HIV to spread. Researchers have also investigated the possibility that cytomegalovirus, a common form of herpes virus, might be the elusive co-factor, but eventually they ruled it out. "It has to be something that's not too obvious," says Dr. Kent Sepkowitz at the New York Hospital-Cornell University Medical Center. "Otherwise, we would have figured it out a long time ago."
Montagnier believes that the co-factor might be a mycoplasma -- a primitive bacterium-like organism. The possible role played by this microbe may help explain one of the mysteries surrounding the origin of AIDS. Studies of blood samples preserved from decades ago show that HIV was present in Africa long before AIDS appeared. What caused the once harmless virus to turn deadly? Montagnier thinks it was a strain of mycoplasma that until recent years was confined to America. Somehow, somewhere, according to his theory, HIV and the mycoplasma got together in a group of humans, and that was the start of the AIDS epidemic.
POWERLESS DRUGS, ELUSIVE VACCINES
If HIV were an ordinary virus, designing drugs to kill it might not seem like an impossible mission. "But it is a much more difficult virus than anyone anticipated," says Myron Essex, head of the Harvard AIDS Institute. "It has many more fancy genes to determine how it replicates. It has positive and negative controls that interact with cellular controls, which allows it to crank up rapidly or remain silent for a long time. It's a very, very unusual virus."
Most important, HIV can easily disguise itself by altering the proteins in its outer coat. When that happens, the job of finding and attacking the virus becomes harder. Even AZT, the most effective drug against HIV, is nowhere near as potent as doctors or patients hoped it would be.
First approved for use in the U.S. five years ago, AZT prevents one of the viral genes from making an enzyme, called reverse transcriptase, that is critical to HIV's reproduction. This action prolongs life by postponing some of the symptoms of AIDS. But in patient after patient, HIV eventually mutates into a form that is less vulnerable to AZT. As a result, the drug's benefits generally run out within 18 months.