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Copyright © 1997 The Seattle Times Company

Tuesday, Sept. 30, 1997

AIDS drugs fail many

by Jim Puzzanghera
Knight-Ridder Newspapers

Despite the hope and excitement surrounding protease inhibitors, a powerful new drug treatment for AIDS, the drugs fail to work in half the people taking them, according to results of a study released yesterday.

The reasons for the failures stem not so much from the drugs as from the people taking them, according to the study.

The study tracked 136 HIV-infected patients in the "real world" of San Francisco General Hospital's AIDS clinic, rather than in controlled scientific studies. And it poured some cold water on growing hopes that protease inhibitors - taken as part of a "cocktail" with other drugs - can stop AIDS in its tracks.

"I don't want to take away from these protease inhibitors. They are absolutely powerful and dramatic drugs," said Dr. Steven Deeks, an assistant professor of medicine at the University of California-San Francisco and the lead author of the study.

"It's just that they are not perfect," he said. "And there are a significant number of people who will likely fail with these drugs."

Scientists have been careful not to call the new treatment a cure, but the news in the past year had pointed in that direction.

There was unprecedented optimism at the 11th International Conference on AIDS in Vancouver, B.C., last summer, followed by reports of dramatic decreases in AIDS-related deaths and the first scientific studies showing the three-drug cocktail could pummel the virus to undetectable levels. Stories of the dramatic recoveries led to a drop in donations to AIDS charities and a flurry of optimistic headlines, such as Newsweek's "End of AIDS?"

But people close to the disease - researchers, advocates and patients themselves - said the study confirms what they had suspected all along.

"We were so starving for good news, and believe me, protease is great news," said Paul Wisotzky, chairman of the board of directors of the San Francisco AIDS Foundation and an AIDS patient himself. "This is a little disheartening, but it really should not be surprising. This is a virus that has eluded almost everything."

Deeks and his colleagues found that 53 percent of the patients seen at the clinic between March 1996 and March 1997 showed evidence that the protease-inhibitor treatment failed after at least six months of therapy. That's far below the failure rates of 10 to 20 percent reported in clinical trials. The new findings were presented yesterday in Toronto at an infectious-disease conference sponsored by the American Society of Microbiology.

The study found that patients who were not helped by the drug therapy had high amounts of the virus already in their system, had developed some resistance after taking antiretroviral drugs in the past, or had problems complying with the complex regimen (from 13 to 26 pills a day, some taken with meals, some without food).

The protease inhibitors - so called becasue they inhibit the enzyme that lets HIV cut itself into smaller segments that grow into mature viruses after replication - are more effective in patients who have not been treated with other AIDS drugs.

Data on use of second drug

Deeks also presented data showing that when a patient failed to benefit from treatment with a first protease inhibitor, success with a second one could be limited.

At San Francisco General's clinic, the AIDS epidemic seems to be splitting in two, Deeks said. About half the patients will see long-term, possible permanent response to the drugs. The other half may see the disease start progressing again after the drugs initially knock it down.

"Society needs to realize this epidemic is not going to go away and we need to continue to devote resources to developing options for new therapy," Deeks said.

He cautioned that the results from San Francisco's public, inner-city AIDS clinic - where most of the patients are in advanced stages of the disease, and many are drug users or homeless people without access to regular meals - could result in higher failure rates than clinics in other locations.

But such conditions are more "real world" than those present in clinical trials, where people who volunteer to be studied generally are healthy and are highly motivated to take the drugs in their precise regimen.

At Stanford University's AIDS clinic, director Andrew Zolopa estimated 25 percent to 33 percent of the patients have seen the protease-inhibitor therapy fail.

`Shouldn't be a surprise'

"It really shouldn't be a suprise to anyone that the drugs are not as effective in the real world as they were in clinical trials where you have highly selected patients," Zolopa said.

"Although these drugs are a very big leap for us in the treatment of HIV. We're still a long way from having this be a disease that can be chronically manged like diabetes."

Continued AIDS research is needed to improve how protease inhibitors work, Zolopa said.

In other developments yesterday:

-- The Food and Drug Administration approved the first-ever combination AIDS tablet. The new pill by Glaxo Wellcome combines the drugs AZT and 3TC - two of the key components, along with protease inhibitors like Crixivan or Norvir, in the AIDS cocktail - which means that patients can get their doses of those drugs in two pills a day instead of as many as eight.

Zolopa said advances like that will make the drug regimen easier to follow.

-- A government-sponosored panel recommended that the drug "cocktails" of protease inhibitors should be used to fight HIV in children.

Donna Shalala, secretary of the Department of Health and Human Services, announced draft guidelines to be subject to a 30-day public comment period. A group of 64 pediatric AIDS experts throughout the country developed the guidelines.

A spokeswoman for HHS said this is the first time the agency has issued AIDS treatment guidelines for children.

The proposed guidelines call for using the powerful drug cocktails in all HIV-infected infants under 12 months of age as soon as doctors have a confirmed diagnosis. Recently, the Food and Drug Administration approved two protease inhibitors - ritonavir and nelfinavir - that are specifically formulated for children.

Information from Newsday is included in this report.