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Transmission of Drug-Resistant HIV Reported


GENEVA — Scientists have found for the first time that strains of the AIDS virus resistant to protease inhibitors and other widely used AIDS drugs can be transmitted from one person to another, it was reported Tuesday at the 12th World AIDS Conference.

Only two individuals with such multiple-resistant HIV have been identified so far. But the cases have startled many because they are the first involving transmission of strains of HIV resistant to protease inhibitors, which sparked a revolution in treatment two years ago.

Scientists did not believe that such highly mutated viruses were capable of passing from person to person. The finding that they are indeed able to do so has potential implications for people who may become infected, experts said.

"This should be a wake-up call for people who continue high-risk practices with the expectation that they can be easily treated if they become infected," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

"We're not talking about a doomsday scenario here, but it is something to be concerned about," said Dr. Frederick Hecht of UC San Francisco, who discovered one of the patients. The other patient was in Switzerland.

As many as one in six newly infected individuals now contracts viruses resistant to the older AIDS drugs, such as AZT.

AZT has been approved for more than 10 years, and HIV quickly develops resistance to it, so researchers are not surprised that resistant strains are circulating from human to human. The proportion of AZT-resistant strains has plateaued at about 16%-17% as other drugs have begun to replace it.

Protease inhibitors, which block an enzyme crucial to reproduction of HIV, were approved in 1996. Their addition to regimens including two or more other AIDS drugs usually renders viral levels in the blood so low that resistance-producing mutations rarely occur.

Some patients do not take all their drugs every day, however, or they take drug holidays--both of which allow mutations to occur. A recent study showed that only 60% of patients took most or all of their AIDS drugs over a seven-day period.

As a result, up to 50% of some groups of patients have viruses in their bodies resistant to many drugs. But laboratory studies hinted that these mutants would not spread easily.

Hecht's results contradict those studies.

In a two-year study of 35 subjects newly infected with HIV, Hecht detected one instance of transmission of such strains. "These [subjects] are hard to find," he said, because it is very difficult to verify that they are newly infected.

His subject was a middle-aged male from the San Francisco area who caught the virus after participating in anal intercourse without a condom. That one act was the only incidence of high-risk behavior that could have produced the transmission, Hecht said.

The virus was shown in laboratory tests to be at least partially resistant to all four protease inhibitors that have been approved for sale, as well as to both AZT and 3TC--in short, to six of the 11 drugs now approved for AIDS treatment. That resistance was confirmed clinically by the inability of treatment regimens containing the drugs to bring his viral levels down.

The virus had a total of 11 separate mutations, four associated with resistance to AZT and 3TC and seven associated with resistance to protease inhibitors. The same mutations were found in a virus isolated from the infected man's sexual partner.

Because so few patients were studied, "We still don't know how frequently resistant strains are transmitted," Hecht said. "But we now know that people can acquire strains with multi-drug resistance, including resistance to protease inhibitor treatment."

The results will be reported at greater length in the July 30 New England Journal of Medicine.

Dr. Sabine Yerly of University Hospital in Geneva reported Tuesday on 67 patients from Geneva and Lausanne, Switzerland, with newly diagnosed HIV infections. One of the patients was infected by a virus resistant to two conventional drugs, 3TC and ddC, and one protease inhibitor, nevirapine.

Six of the other patients, however, were found to be wholly or partially resistant to one or more protease inhibitors, suggesting that resistance to these valuable drugs may become more common in the future.

These cases "should certainly not be regarded simply as an esoteric anecdote," Fauci said. "On the contrary, trends are born from anecdotes, and [these reports] should deliver a loud wake-up call on many fronts in the battle against HIV."

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