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| health > AIDS > story page |         |
HIV resistance may not be cause of drug treatment failure
January 11, 2000
By Sarah Yang (WebMD) -- Two studies published this week in the Journal of the American Medical Association may lead some to rethink how HIV, the virus that causes AIDS, rebounds and how treatment failures are handled. It's a disheartening scenario: Months or years after initial success in HIV drug therapy, the weapons that science developed to battle the disease are no longer effective, and the virus count clambers back up. Whether the problem lies in adherence to the complex drug intake regimen or the development of resistance to the drugs or both, patients run out of choices as one "AIDS triple cocktail" treatment after another fails. In one study, French researchers found that for patients who are trying their first course of drug therapy, adherence problems appear to play a greater role than resistance in treatment failure. The researchers assigned patients who had successfully completed three months of intensive triple-drug therapy to three maintenance-phase groups. Patients either continued the three-drug regimen or took combinations of AZT and 3TC or AZT and the protease inhibitor indinavir. Researchers identified 58 patients whose viral counts increased during the maintenance phase of the trial and matched them with patients whose viruses remained suppressed. They then tested for the presence of mutations known to cause resistance to the drugs patients were taking. "We did not find any indinavir or (AZT) resistance mutations in people taking these drugs," said Francois Raffi, M.D., professor of microbiology at Bichat-Claude Bernard Hospital in Paris and study coauthor. She said resistance was found for 3TC, but it was found in both groups taking 3TC and was unlikely to have been a major cause of viral failure. But when the researchers compared adherence levels, determined by counting pills between visits and measuring the blood levels of indinavir, significant differences were found. Patients whose virus counts resurged while taking AZT and indinavir had lower adherence rates than patients whose virus loads were suppressed. Raffi cautioned against extending the results to all HIV patients, noting that the viral load had rebounded for patients in her study shortly after starting therapy. AIDS experts say the study indicates the need for health care providers to work harder to support patients during the grueling regimens. "The first reaction you should have if the patients are not benefiting is to really, in a nonjudgmental way, explore if they're taking the drug correctly," said Paul Volberding, M.D., professor of medicine at the University of California, San Francisco, and a renowned AIDS expert. "It's not the patient's fault; it's the fault of physicians not communicating more effectively the importance of taking the drugs correctly. "We're making life impossible for these patients because we make the regimen so complicated." But resistance may still develop for patients who do follow the regimen, experts say. In the other study, researchers at the University of California, San Diego, found that in some of those cases, it may only be necessary to change one drug in a multi-drug treatment. Tests revealed mutations associated with resistance to 3TC in patients who had failed during a maintenance phase of drug therapy. But they also showed that the virus was still responding to indinavir. "We previously thought resistance to all drugs in a regimen is the reason drug cocktails don't work," said Diane Havlir, M.D., associate professor of medicine at the University of California, San Diego, and study leader. The study results could lead to a more "efficient" use of the available drugs, she says. That efficiency would be valuable, since the spectrum of therapy options quickly narrows as treatments fail and patients develop cross-resistance to other drugs, said Mark Feinberg, M.D., associate director of the Center for AIDS Research at Emory University in Atlanta. Feinberg said the results are "encouraging" since the "recommended practice" is to change two, and ideally all three, components of a drug regimen if it is failing. But he said it would be premature to change the current practice before other clinical trials verify the efficacy of changing fewer than two components in a regimen. He also notes that current treatment standards differ from those of many patients in the two studies. "Patients (in the study) went through an induction and maintenance phase (consisting of fewer drugs), while patients now continue on a chronic three-drug therapy," Feinberg said. "If somebody is failing chronic administration of three drugs, it could be that they have mutations from all of the components."
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