Newsday - September 22, 1999
Laurie Garrett, Staff Writer

The findings, some of which are published today, raise troubling concerns for both HIV treatment and public health control of the epidemic. Since all three research groups discovered highly multidrug-resistant virus forms that have surfaced within the last 18 months, the fear is that this is the beginning of a trend that could render treatments useless to those infected in the future.

"These are not wimpy viruses that cannot be transmitted," as was previously popularly believed, Dr. Martin Markowitz of the Aaron Diamond AIDS Research Center in Manhattan said. "From a public health point of view it means we need to identify drug-resistant cases early. And people who are on HAART [Highly Active Anti-Retroviral Therapy] need to know that they can still transmit viruses." The discovery of the spread of drug-resistant HIVs comes at a time when public health authorities in New York City, San Francisco, Chicago and Seattle are reporting evidence of increased unsafe sexual activity among gay men, and resultant rises in gonorrhea and syphilis in those communities. More gay men, it seems, are abandoning the use of condoms amid widespread misperception that the HAART drugs introduced into widespread use in 1996 have rendered the disease treatable and less dangerous.

Markowitz led a team of New York City and Los Angeles researchers who analyzed HIV found in 77 men and three women who had been infected, on average, for less than two months. This means that the scientists were able to recover from the patients' blood the same virus strains that originally entered their bodies sexually. Sixteen percent of these people had viruses that carried known mutations that confer resistance to HAART drugs. Even more of the patients-26.8 percent-had viruses that were able to grow in test tubes filled with various anti-HIV drugs. That means that there are more genetic types of resistance in HIV than scientists have so far been able to pin down.

Most critically, 3.8 percent of the individuals had multidrug resistance-one was more than a thousand times less sensitive than normal to an entire class of HAART drugs.

"The transmission of drug resistance should not be considered insignificant,"' Markowitz, whose findings appear in today's issue of the Journal of the American Medical Association, insisted. "Sixteen percent resistance in any organism is very significant." Also in today's Journal are the results of analysis of viruses taken from 129 men and 10 women within 12 months of their infection. These individuals were infected between 1989 to 1998 in San Diego, Los Angeles, Denver, Dallas or Boston. In this group, too, 26 percent of the individuals carried drug-resistant viruses and 2 percent had highly multidrug-resistant strains.

"The numbers of newly infected patients infected with multidrug-resistant virus is small-just two percent," study director Dr. Susan Little of the University of California in San Diego said. "But, how will these numbers change with time? All three of our patients with multidrug-resistant viruses were infected in 1998." Indeed, all of the studies show that the most highly drug-resistant strains were recovered from patients who were infected in the last 18 months. Since HAART only went into widespread use in the United States in 1996 and Europe in 1997 it may be that, "We are only seeing the tip of the iceberg and should see increasing numbers of highly resistant strains with time. We don't know yet," Little said.

Geneva University Hospital researcher Dr. Luc Perrin last month published similar findings in Lancet, a British medical journal, based on a study of 82 newly infected French and Swiss patients. Keeping in mind that HAART has been in widespread use in those countries for about a year less than in the United States, it's interesting that Perrin's drug-resistant pool was just 11 percent of those patients. But 4.3 percent of them were infected with HIVs that are resistant to the newest class of drugs-protease inhibitors-compared to 9 percent resistant to the oldest drug, AZT. And the one patient who had highly multidrug-resistant HIV in Perrin's group was infected in 1998.

Perrin wrote that this finding presents "a serious threat to the management of antiretroviral therapy," and he advocates resistance testing of all HIV patients, as a matter of routine.

Dr. Roger Pomerantz of Thomas Jefferson University in Philadelphia is adamantly opposed to such testing. He argues in today's Journal that too little is known about the clinical significance of any particular HIV mutation to be able to do anything useful with the test results. And the tests themselves, are very hard to perform, Markowitz added, and highly vulnerable to laboratory contamination.

But last year Pomerantz published disturbing evidence that HIV patients who are doing very well on HAART, and have no detectable HIV in their blood, can still spread the virus to their sexual partners.

"They are not uncontagious," Pomerantz said in an interview. "So obviously discovery of transmission of drug-resistant viruses is a problem." Two weeks ago at the National HIV Prevention Conference in Atlanta, Dr. Jeffrey Koplan, director of the Centers for Disease Control and Prevention in Atlanta, hailed HAART as a "tremendous public health accomplishment." When questioned on this point in an interview, Koplan added, "I think you're hard-pressed not to say it's a public health triumph when people can live longer." But, HIV experts note, there is a big difference between antibiotic treatments for, say, tuberculosis and HAART for HIV. The antibiotics are curative, and thus decrease the size of the contagious TB population. HAART, in contrast, is not curative and has greatly increased the size of the population of Americans and Europeans living today with HIV.

Now that there is evidence that members of this HAART population can transmit HIV to their sexual partners, in some cases passing mutant, highly drug-resistant forms of the virus, the public health implications of drug treatment may be less than triumphant.

"Clearly HAART was a great boon for medicine," Pomerantz said. "For public health, though, it's a challenge, maybe an obstacle." Little argues that the results aren't yet conclusive. She wants more studies.

But, "the more widespread the use of potent therapy might be, the greater the public health concern could be. We don't know that-yet," Little concluded.
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