Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
San Francisco Chronicle; Monday, June 1, 1998
Sabin Russell, Chronicle Staff Writer
There are 11 major AIDS drugs approved by the Food and Drug Administration, and combinations of these drugs are credited with a dramatic drop in deaths. But the latest study implies that even more anti-viral weapons are needed.
"There is a problem with drug resistance, and we can't fool ourselves," said Dr. Robert Shafer, lead author of the study to be published today in the Annals of Internal Medicine.
Shafer and colleagues at Stanford University Medical School found that the viral strains carried by patients in the study can outwit nearly every major AIDS medicine on the market. In their work, they probed the genetic fingerprints of the AIDS virus taken from four patients who had not responded to a battery of drug combinations. The four men had been battling AIDS for between four and nine years.
The careful molecular analyses of these strains showed that they had all mutated into forms known to be resistant to 10 of the 11 approved AIDS drugs.
A follow-up study, not included in the Annals of Internal Medicine report, determined that 20 percent of 400 long-term AIDS patients tested in the Bay Area carried strains of HIV -- the human immunodeficiency virus that causes AIDS -- that have built-in resistance to "the majority of anti-HIV drugs."
San Francisco AIDS Foundation spokesman Derek Gordon said the lab results explain how and why the drug combinations are not working for everyone. "People seem to have gotten a message that we can relax, that the epidemic is under control," he said. "This is scientific evidence that relaxing is the last thing we should be doing."
Shafer said patients who have been diagnosed more recently and were given the latest combinations of AIDS drugs are less likely to develop resistance than those who have been taking AIDS drugs for years -- often as soon as they became available on the market or in clinical trials.
"The problem is that most people don't fit into the category of just diagnosed and able to tolerate three or four drugs for the rest of their lives," Shafer said.
Existing AIDS drugs attack one of two vulnerable targets in the AIDS virus, preventing it from replicating. Drugs of the AZT family block a protein called reverse transcriptase; newer drugs called protease inhibitors block an enzyme called protease.
The Stanford researchers found, however, that all the viral samples contained eight different genetic mutations that allow the human immunodeficiency virus to evade the AZT family, and seven different mutations that can overcome protease drugs.
The viruses were vulnerable to only one approved drug, the reverse transcriptase inhibitor Viramune, sold by Boehringer Ingelheim. It works against the same target as AZT but is made from a different class of chemicals. None of the four patients took that medication -- the test was done on human cells grown in a test tube.
Two other drugs that have not yet won FDA approval, Dupont Merck's Sustiva and Gilead Sciences Preveon, were also effective in test tube studies. Shafer said that, had the patients taken these drugs as well, there is every reason to think that viral resistance would develop for these drugs, too.
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