BARCELONA (Reuters Health) - Drug resistance has returned as a mounting problem in HIV/AIDS treatment, after a brief lull in the late 1990s, according to new figures released on Saturday.

The introduction of triple-drug therapies in the mid-1990s revolutionized the treatment of the disease for thousands of those infected in Western countries, allowing them to return to relatively normal lives.

But the virus is evolving new ways to outwit medicines and a growing number of people are now being infected with strains that are already resistant to one or more of the three widely used classes of antiretroviral drugs.

Dr. Frederick Hecht of San Francisco General Hospital in California and colleagues studied 225 patients with recently acquired HIV infection between 1996 and 2001. In 2000-2001, 16% of new cases were clinically resistant to one or more drugs, compared to 9.9% in 1998-1999 and 21% in 1996-1997.

Genetic fingerprinting of virus found in patients' blood showed that mutations linked to resistance to non-nucleoside reverse transcriptase inhibitors--a widely used and potent type of AIDS medicine--increased from zero to 13.2% between 1996-1997 and 2000-2001.

At the same time, the researchers found mutations linked to resistance to protease inhibitors had grown from 2.5% to 7.7%, they report in a special edition of The Journal of the American Medical Association.

The same genetic analysis showed resistance mutations to the class of AIDS drugs that includes AZT, known as nucleoside reverse transcriptase inhibitors, returned to levels over 20% after dipping to 7% in 1998-1999.

Hecht told reporters ahead of the opening of the biennial world AIDS conference that there was a danger of complacency if people believed HIV could be easily kept at bay by popping a few pills.

"There has been a decrease in caution about avoiding HIV infection and an increase in riskier sexual behavior...on the assumption that HIV is much more readily treated now," he said. "That idea needs to be called into question because some people are becoming infected with virus that is going to be much more difficult to treat."

Hecht said San Francisco was in the vanguard of HIV/AIDS treatment and the worrying trend of rising drug resistance was likely to be replicated elsewhere.

"I think we are going to see continued increases (in resistance) over the next 2 years," he said.

The problem may have implications for developing countries, many of which are expected to rely heavily on combinations of relatively cheap reverse transcriptase inhibitor drugs rather than more expensive protease inhibitors.

In the United States, the issue of drug resistance is forcing doctors to test ever more complex regimens.

Dr. Hammer of Columbia University College of Physicians and Surgeons, New York, reported on another clinical trial showing for the first time that adding two protease inhibitors, rather than just one, to drug cocktails could help patients who had failed to respond to other treatments.

Hammer's group studied 481 patients with moderately advanced immunodeficiency who had been exposed to as many as three protease inhibitors. They gave participants a cocktail including the protease inhibitor amprenavir, with abacavir, efavirenz and adefovir dipivoxil, to which they added either another protease inhibitor or an inactive placebo.

Adding a second protease inhibitor saw 35% of patients reduce the amount of virus in the blood to below 200 copies per millilitre, compared to 23% among patients who were only taking one protease inhibitor.

SOURCE: The Journal of the American Medical Association 2002;288:169-180, 181-188.

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