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HIV Strains Resist Leading Drug Therapy

Study finds 3.3% of patients carry a copy

MONDAY, Nov. 5, 2001 (HealthDayNews) -- A fishing expedition for drug-resistant AIDS has found that some HIV-positive patients carry mutant strains of the microbe that show signs of resisting frontline treatment against the virus.

New research says more than 3 percent of people with HIV who have never been treated for their infection still have these limbo forms of virus. The mutations don't automatically confer resistance to AZT, the first effective drug against AIDS, but they do make it more likely once the medication is used against the virus.

"These intermediate mutations do not affect drug susceptibility, but they are more prone to developing resistance" in lab experiments, says J. Gerardo Garcia-Lerma, an HIV expert at the Centers for Disease Control and Prevention and lead author of the study. "What is needed is to see if the prevalence [of the mutant strains] increases over time or not. That is one of the key questions."

A report on the findings appears in the Nov. 6 issue of the Proceedings of the National Academy of Sciences.

The CDC estimates that between 650,000 and 900,000 people in the United States have HIV, but those figures are based on mathematical models and not a true accounting. Although the government doesn't track how many people receive HIV treatment, private sector estimates put the number at approximately 430,000.

AZT, also known as zidovudine or Retrovir, was approved in 1987 to treat HIV infection. The drug, which forms one third of a common AIDS drug "cocktail," is a reverse transcriptase inhibitor, meaning it blocks the enzyme that enables HIV to convert host cells into virtual virus factories.

The first cases of AZT-resistant HIV appeared in 1992. These organisms have developed mutations that outmaneuver the drug and allow them to replicate unhindered. But without continued pressure from the drug, they revert back to susceptible forms of the virus.

In the new work, Garcia-Lerma and his colleagues looked for other signs of resistant virus in 603 HIV-positive patients who'd never been treated with AZT. About 3.3 percent of them had one of four new mutations in the reverse transcriptase gene that were not present in the normal strain. They were also much more common than known resistance genes.

The mutations, at a spot on the reverse transcriptase gene called codon 215, don't give the virus resistance to AZT if left alone. But when provoked with the drug in a test tube they develop immunity to it after three to four weeks, the researchers say. "Since [codon 215] is a key position, any mutation in this position will occur really fast and will result in resistance," Garcia-Lerma says.

The researchers say it's not clear whether the new, intermediate mutations arose naturally, or if they reverted from strains of AZT-resistant HIV after being acquired.

Dr. Daniel Kuritzkes, an AIDS expert at the University of Colorado Health Sciences Center in Denver, says the new findings may lead to changes in the drug concoctions used to treat HIV infection. But how that happens remains a major question.

"When we use multi-drug therapy even in the setting of AZT resistance, it's difficult to show a big impact of AZT resistance because the drugs [in combination] are so potent," says Kuritzkes, author of an editorial accompanying the journal article.

However, in patients with the limbo mutations, he adds, "I do think the better part of valor would be to avoid using" AZT and related drugs in the cocktails.

What To Do

To learn more about HIV and AIDS therapies, visit the HIV/AIDS Treatment Information Service or Project Inform.

You can also try the Centers for Disease Control and Prevention.

SOURCES: Interviews with J. Gerardo Garcia-Lerma, Ph.D., senior service fellow, Centers for Disease Control and Prevention, Atlanta; Daniel Kuritzkes, M.D., associate professor of medicine and microbiology, University of Colorado Health Sciences Center, Denver; Nov. 6, 2001, Proceedings of the National Academy of Sciences
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