Hiv's Raw Aggression

For such a deadly virus, hiv has always seemed a rather sluggish one. Infected people can go a decade or more without showing symptoms, so experts have reasoned that the bug must lie dormant in the cells it infects until some unknown crisis pushes it into action. Two new studies have now radically changed the picture, showing that HIV is not a subtle intruder but a rabid aggressor that battles the body from the first day of infection. The discovery -- published in the journal Nature by researchers at the University of Alabama, Birmingham, and at New York's Aaron Diamond AIDS Research Center -- won't produce new treatments right away. But as Nature's editors boasted in a statement last week, it "completely changes our understanding of what's going on."

HIV's basic mode of action is no mystery. Scientists have known for a decade that the virus infects immune cells called T lymphocytes (more precisely, CD4 lymphocytes) and uses their machinery to churn out copies of itself. The virus has a heyday during the first weeks of infection, before the body mounts an immune response, but it soon forms a stable relationship with the host. Though HIV levels and CD4 counts change ever so slowly over the next several years, they don't stand still. Over time, HIV becomes more and more prevalent in the blood, and the number of CD4 cells dwindles. Finally the immune system crashes. The point of the new studies was to determine how the virus and the body treat each other during that gradual progression toward AIDS.

The strategy was simple but ingenious. By administering antiviral drugs and monitoring the effects, the researchers were able to calculate the typical rates at which HIV and its target cells are wiped out and replenished. During drug treatment, the amount of HIV in patients' blood fell byas much as 99.99 percent. And as their "viral loads" dropped, their immune systems quickly replaced huge numbers of lost CD4 cells. No one expected the benefitsto last; after just two weeks of drug treatment, resistant forms of HIV were flourishing in the patients' bodies. But the quick rise in CD4 cells during treatment suggested that infected people generate 2 billion of those cells every day -- even at advanced stages of illness. And the rapid appearance of drug-resistant HIV showed that the virus, far from lying dormant, replicates furiously to hold the line against the immune system. The reason the infection progresses so slowly is that the combatants are so closely matched.

Why the virus ultimately wins is still a mystery. Some experts believe the immune system in effect eats itself as it dutifully destroys its own infected cells. Others suspect that HIV simply kills lymphocytes at a slightly faster clip than the immune system can replace them. In either case, the new findings hold clear practical lessons. Since the immune system appears so resilient, says Dr. David Ho of the New York team, researchers shouldn't concern themselves with repairing it. They should focus on crippling the virus -- and crippling it early, before its progeny become too varied to contain. Those are enormous challenges, but thanks to the new discovery, scientists can now assume they're the right ones.

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