AIDS virus outrunning drugs meant to contain it--but BYU research outlines new plan of attack for drug makers
Contact: Michael Smart, 801-378-7320 [email protected]
Provo, Utah--Brigham Young University researchers have demonstrated that the AIDS virus is evolving so fast in some patients that it has become immune to the heralded "AIDS cocktail," a commonly prescribed multi-drug therapy. But the good news, the researchers say, is that HIV is mutating the same way in each patient, giving drug makers a new bull's-eye for the next generation of AIDS drugs.
"Combination drug therapies are clearly extending lives and improving the quality of lives of HIV-infected patients, and some scientists have purported the cocktail to be a cure," said Keith A. Crandall, assistant professor of zoology at BYU. "But our study shows that a cure is further away than we thought. The virus is still evolving, and the HIV population is acquiring drug-resistant mutations."
In a paper in the March issue of Molecular Biology and Evolution, Crandall reports how he, in collaboration with the National Institutes of Health and the National Cancer Institute, analyzed the DNA sequences of certain genes taken from eight patients who had been taking combined drug therapies for at least two years during the study. He found significant evolution of the virus over the course of one to two years, even in the three patients who had only small traces of HIV in their systems. In five of the patients, the virus changed so much that it was no longer affected by the drugs--in scientific parlance, the virus "escaped" drug therapy.
The HIV in the patients could have evolved into any one of thousands of possible mutations, but Crandall found that, in each of the five, it had mutated into exactly the same new version, which he describes using genetic code in his paper. What appear to the untrained observer to be random lists of different combinations of letters are actually blueprints for pharmaceutical researchers targeting the new, cocktail-resistant mutation of HIV.
"This is the first indication that the HIV mutations are evolving in parallel," said Crandall. "Hopefully new drugs can catch up to this elusive virus."
Scientists at the National Institutes of Health took blood samples from the study participants and passed them to colleagues at the National Cancer Institute, who sequenced the DNA. Crandall was assisted in the analysis of the sequence data by Chris Kelsey, who at the time of the study was a BYU zoology major.
The NIH, which funds research applied to human disease, supported this study, Crandall said, "because they see evolutionary biology as a fruitful area, particularly with regard to drug resistance."
As an evolutionary biologist, Crandall attempts to characterize genetic change over time and use the results to predict what will happen to patients in the future. He compared HIV to his other research specialty, the evolution of crayfish, to explain why the virus is such an ideal subject for an evolutionary biologist to study.
"Because of HIV's high mutation rate, it provides a unique opportunity to study the processes of evolution," he said. "I'd have to wait a couple million years for crayfish to evolve as much as HIV does in a year."
Crandall is concerned not only with HIV's drug resistance, but also with other viruses and bacteria. Physicians have over-prescribed antibiotics and anti-viral agents, inadvertently strengthening germs, he said. Patients are also to blame, said Crandall, when they stop taking antibiotics before they have completed the full dosage. This leaves a small amount of bacteria that is strong enough to resist the drugs in the patient's system--bacteria that then may be passed on to others.
"We now have superstrains of bacteria that are resistant to any antibiotics we can throw at them," he said. "The problem is serious and will continue to get worse until physicians have a better understanding of evolutionary biology and patients follow their doctors' instructions."
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