The Wall Street Journal - Friday, February 5, 1999
Michael Waldholz, Staff Reporter of The Wall Street Journal

Several separate research investigations, using two new types of sensitive diagnostic tests, found evidence suggesting that about 20% to 30% of individuals newly infected with the AIDS virus are carrying forms of the virus that are already resistant to one of the 13 different medicines used in the combination-drug therapy revolutionizing AIDS treatment.

Result of Combination Therapies

One of the studies released at the end of the four-day AIDS science conference here found evidence indicating that perhaps 10% of newly infected people are being exposed to viruses resistant to at least two drugs. The surprisingly high incidence of resistant virus in circulation in the U.S. is largely seen as a result of the widespread -- and sometimes improper -- use of the new drug therapies, as well as a testament to the virus's stubborn ability to alter its chemical structure to thwart the drugs' effectiveness.

"Suffice it to say, resistant virus is prevalent in the population and is being transmitted," said John Mellors, a research physician at the University of Pittsburgh School of Medicine. Speaking at the Sixth Conference on Retroviruses and Opportunistic Infections, Dr. Mellors added that the transmission of resistant virus is "not common, but it is likely to spread, and the frequency will go up."

Several top AIDS physicians attending the meeting said the new findings were worrisome but not surprising. As with most infectious microbes, HIV, the AIDS virus, can mutate into versions that are no longer vulnerable to medicines. Doctors say this most often occurs in patients who don't adhere rigidly to the drugs' daily dosing regimen, or were among the portion of patients in whom the drugs weren't able to significantly reduce virus levels. As a result, even when under attack by three or four anti-HIV drugs at once, low levels of the AIDS virus that remain in the bloodstream can eventually replicate into mutant versions that are invulnerable to one or more of the drugs.

The new research confirms anecdotal evidence first reported in the summer that some people are now passing along to others the virus that has become resistant to one or more drugs. The report also comes amid reports of rising levels of unsafe sex among men.

Push for New Tests

The circulation of drug-resistant HIV, while a sobering public-health concern, is being viewed by researchers here as a persuasive argument for the widespread introduction of two recently developed, and relatively expensive, tests based on cutting-edge biotechnology. Using two separate gene-based detection methods, the tests can warn doctors if an individual is carrying a resistant virus. In many instances, the tests also can identify precisely which of the 13 anti-AIDS drugs aren't likely to be effective and which will likely still work.

"The rising resistance problem means that these new tests need to become standard additions to managing the infection," said Robert Schooley, a researcher at University of Colorado Health Sciences Center in Denver. "With the new tests, we should be able in most cases to still provide patients with effective drug therapy," he said.

The new tests have been developed by three relatively young biotechnology firms. One of the tests, called a genotype, can probe a virus's genetic makeup, identifying altered bits of genetic material that allow the virus to become resistant to a particular drug. The other test, called a phenotype, detects whether a virus is still able to grow in cells when mixed into a test-tube solution containing a specific drug. If the virus grows, it means it is resistant to the drug.

In one study using a phenotype test developed by a closely held Brussels company named Virco, researchers found that 21% of 91 blood samples taken from HIV-infected U.S. army personnel from around the U.S., who had never undergone drug therapy, contained viruses resistant to at least one type of drug. Virco's phenotype test is being sold in the U.S. and Europe for about $800; its relatively high price results from the need to culture the virus numerous times over several weeks in the presence of all 13 drugs, according to Virco's co-founder and chief executive officer, Paul Stoffels.

A second report using a phenotype test developed by ViroLogic Inc., a closely held firm in South San Francisco, Calif., found that 28% of 69 samples collected in the past three years from five U.S. cities contained drug-resistant viruses. That test, which ViroLogic expects to begin marketing to doctors later this year for about $900, found that seven of the samples contained viruses resistant to two or more drugs. These samples also were taken from subjects newly infected or who had never been treated, indicating that they were infected by virus already resistant to the drugs.

Visible Genetics' Effort

A third report made use of a genotype test from Visible Genetics Inc., a publicly traded company in Toronto. In that study, researchers gathered blood samples from long-treated patients whose virus levels were rising, suggesting that the virus in their blood had mutated into a resistant strain. At present, when virus levels rise, most doctors are uncertain about which drugs may still be effective. In the Visible Genetics test, researchers were able to recommend drugs that were able to significantly reduce the viral levels in many patients. John Stevens, chief executive officer of Visible Genetics, said the company hopes to get Food and Drug Administration approval later this year to sell a kit for its test to clinical laboratories. He said the test may be priced between $500 and $600.

The new tests are somewhat controversial, because they are expected to strain government and private AIDS insurance programs already groaning under the combination-drug therapies that can cost $10,000 or more a year. But Douglas Meyers, an infectious-disease physician at Henry Ford Hospital in Detroit, who helped run the Visible Genetics study, said, "Resistance means these tests will become an integral part of treating HIV."

Separately, DuPont Co. reported that its drug Sustiva appears to be as effective as recently introduced protease inhibitors when it is substituted for them in the combination-drug therapy for AIDS. Sustiva, approved last year, works differently than protease drugs. Some doctors are hopeful it won't cause some of the side effects associated with long-term use of protease inhibitors.
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