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Structured Treatment Interruption

HIV evolves rapidly within each patient's body, and viruses with mutations that confer resistance to antiviral medications can soon dominate. But these mutations usually come with a cost - viruses that have them are less vigorous, and if the medications are withdrawn, the wild-type, drug-susceptible viruses once again have a competitive edge. Researchers are cautiously testing the idea that patients whose viral population is highly drug-resistant may be able to harness this evolutionary process by taking carefully monitored "drug holidays." Video segment from Evolution: "Darwin's Dangerous Idea". Featured participants: Clarence Johnson, Veronica Miller, Michael Saag.

Credits: 2001 WGBH Educational Foundation and Clear Blue Sky Productions, Inc. All rights reserved.

Structured Treatment Interruption

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4 min, 51 sec

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Structured Treatment Interruption:

We think of evolution as requiring thousands, tens of thousands or millions of years to make significant changes - and often, it does.

But evolution can also occur in a relative eyeblink. That's the case when the human immunodeficiency virus (HIV) becomes locked in a survival struggle in the body of a patient who's taking powerful anti-viral drugs.

It's evolution in fast-forward mode. The virus, replicating billions of times a day, can acquire new mutations at lightning speed: eventually, some of the genetic changes enable the virus to resist even the most powerful drugs. These drug-resistant viruses come to dominate the population and threaten the patient's life.

However, evolution can work in the patient's favor, too, as Dr. Veronica Miller and other researchers have discovered recently. Miller, treating a patient whose population of HIV virus had become drug resistant, agreed to stop the drugs temporarily, which would at least eliminate their toxic side effects. This was a radical step. Patients are warned they must never miss a dose of drugs such as protease inhibitors: now the patient was told he could stop altogether. Miller was amazed to find that when the virus population no longer was under selection pressure from the drugs, the population reverted to the non-resistant "wild-type" form. It had, in effect, evolved backward when the resistant mutations no longer were beneficial.

Then, when the drugs were started again, they had regained their ability to kill the now-vulnerable wild type HIV. Although the patient's body now harbored more virus, and his immune system was weakened by the "drug holiday,'' it was actually a good development. The evolutionary struggle was now running in favor of the drugs - and the patient. Because they were no longer resistant, the virus could be kept in check by the drugs. The cycle can repeat itself with evolution see-sawing first one way, then the other. "The virus replicates so rapidly that evolution happens really in front of our eyes as we treat the patient,'' says Miller.

It's not clear yet whether this strategy, termed "structured treatment interruption'' can be used to extend patients' survival, but some doctors are cautiously trying it, in hopes it will keep their patients alive until new treatments are available.

The strategy "remains unproved and potentially dangerous,'' warned experts in a journal of experimental AIDS treatments. Until larger studies are completed, the value of structured treatment interruption won't be known. In any case, the discovery has revealed another dramatic instance of evolution in action.

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