SIGHTINGS


 
Resistance To AIDS Drugs
Building - Mutated Strains Abound
By Maggie Fox
Reuters News
2-4-99
 
CHICAGO (Reuters) - AIDS experts got another piece of bad news on Thursday - strains of the virus that resist one or more drugs from the very start are spreading.
 
That means that the minute some people get infected, there will be some drugs that are probably a waste of time.
 
Now the question is will it be worth testing these patients to find out which drugs their virus is resistant to, and tailor their prescriptions accordingly?
 
Doctors attending the Sixth Conference on Retroviruses and Opportunistic Infections in Chicago were debating this even as they grappled with the frightening prospect of a "super" HIV virus that resists all known drugs.
 
No one has found one of these yet. But the trend is clear.
 
"The virus can evolve resistance to members of each class of drug," Dr. John Mellors of the University of Pittsburgh said at a news briefing. "Given enough time, it can develop cross-resistance to all members of each class."
 
What is worse is that it is becoming clear that people are passing on these resistant forms of the virus.
 
Mellors said several studies have shown that 3 percent of all newly infected HIV patients have a strain that resists one of more of the oldest and most standard drugs, the reverse transcriptase inhibitors such as AZT and 3TC.
 
Based on studies presented at the conference, Mellors estimates that 5 to 15 percent of all HIV patients have strains that are resistant to the newest class of drugs, the non-nucleoside reverse transcriptase inhibitors (NNRTIs).
 
And between 1 and 10 percent have a strain that resists the the powerful drugs known as protease inhibitors that have been credited with making the multi-drug cocktails really work.
 
"Resistance is prevalent in the population and it is being transmitted," Mellors said. Once that happens, it will spread - just as bacteria first evolved resistance to penicillin, then to newer classes of drugs.
 
"We need a broad-based international surveillance program for resistance," Mellors said. "The level of concern is rising."
 
Two researchers reported on mothers who transmitted versions of the virus that resisted several drugs to their babies.
 
There is some good news. Tests can show when people are infected with a drug-resistant strain, and it could help doctors tailor their treatment accordingly.
 
Now when patients start failing treatment -- when, despite the drugs, the virus starts to show up in the blood and their immune cells start to disappear -- most doctors put them on a whole new cocktail.
 
But a surprising study showed this may not be necessary.
 
Dan Holder and colleagues at Merck Research Labs in West Point, Pennsylvania were examining patients trying out their drug, Crixivan, along with Glaxo-Wellcome's AZT and 3TC. The combination had stopped working in many of them.
 
Tests showed that in 70 percent of them, the virus had evolved a resistance to AZT or 3TC or both. But only about 17 percent of the patients had also evolved resistance to Crixivan, also known as indinavir, which is in a different class of drugs, the protease inhibitors.
 
"The important message from this study is that it is not necessarily the case that you would want to go off all the drugs if you are experiencing failure," Jon Condra, a virologist at Merck, said in an interview.
 
But Mellors also noted that the tests necessary to determine resistance are expensive, and may not clearly indicate whether a person will not do well on a specific drug.
 
Some tests have shown a strain of virus should resist drugs but the patients are still doing well on their drugs.
 
Dr. Brian Gazzard of London's Chelsea and Westminster Hospital told the conference it is probably too soon to start testing patients as a matter of course. But he and others said it might be a good thing to test mothers, for instance, to help prevent the transmission of resistant virus to their babies.
 
And maybe people who have just been infected could be tested so they do not start on drugs that will be a waste of time. Gazzard said cost may not be a good argument. "Compared to the cost of a week's treatment with antiretrovirals, the cost is a drop in the bucket," he pointed out.





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