Miami Herald - Monday, December 11, 1995
Sandra Jacobs, Herald Health Writer

For some, saquinavir may extend life. Others, he has been telling: Wait. "It's the first of a wonderful class of drugs," says Stein, who treats AIDS patients in Miami. "And what's coming is even better."

Saquinavir is one of a new group of AIDS drugs called protease (pronounced PRO-tee-ace) inhibitors. The protease drugs aren't a cure. But they are expected to become part of a virus- fighting strategy combining multiple drugs to slow the progress of the disease.

"What you're doing is buying time -- maybe extra years," says Dr. Anthony La Marca, who treats HIV patients in Fort Lauderdale. "How many varies from person to person." As the drug doses and combinations are fine-tuned, he says, HIV infection may be held in check for years.

"You'll be able to live a healthy life, be working and productive, and not worry about full-blown AIDS," says La Marca. "It's not a cure, but it may enable people to live longer with HIV."

La Marca and his patients were involved in early tests of saquinavir, which was approved by the U.S. Food and Drug Administration on Thursday. Saquinavir -- now being sold under the brand name Invirase -- and its maker Hoffman-La Roche of Nutley, N.J., join a race to the marketplace involving more than a dozen drug-makers working on different protease inhibitors.

The new drugs work by blocking production of an enzyme necessary for HIV to replicate. For HIV to reproduce, the virus creates a piece of protein. It uses the protease enzyme to cut that protein into pieces that become active HIV. By blocking protease, the protein remains in one long immature string -- unusable and noninfectious.

In the fight against AIDS, this is a significant step. AIDS is now viewed as an ongoing battle between the fast- replicating virus and the body's disease-fighting CD4 cells. At first, the body's constant replenishment of CD4 cells (also called T-cells) keeps the disease in check. Eventually, though, the virus overwhelms them. So, AIDS therapy is based on keeping the CD4 cells ahead by slowing reproduction of the virus.

Protease inhibitors are being tested in combination with AIDS drugs including AZT, ddC and 3TC -- all of them called nucleoside analogs, which work by blocking a different protein crucial to HIV production. The strategy is to attack HIV in as many vulnerable points as possible. That's important because, since the virus mutates so quickly, it becomes resistant to any single drug. Researchers are finding that when the virus mutates to escape one drug, it may become more vulnerable to another, says Dr. Margaret Fischl, director of the comprehensive AIDS program at the University of Miami School of Medicine.

"The sequence and combination of drugs is being looked at to considerably knock out the virus," says Fischl.

AIDS researchers are concerned that resistance to one protease inhibitor may bring resistance to others. That's why Stein is recommending that patients who aren't extremely sick not take saquinavir and, instead, wait for other, potentially more effective protease inhibitors. Hoffman-La Roche, though, says it does not expect resistance to other protease inhibitors to be a problem. Michael Willis, who has a very low count of CD4 cells and numerous AIDS complications, says he wants to try saquinavir, if his doctor agrees. "It's supposed to be beneficial for those of us in the late stage," says Willis, 43, events coordinator for the People With AIDS Coalition in Dade County. "We don't have time.

If something looks promising and my doctor says it may have benefit, believe me, I'll jump on it." For patients at earlier stages of the disease, La Marca, the Fort Lauderdale doctor, is optimistic that early treatment involving protease inhibitors combined with other drugs will keep the virus in check for years, maybe even decades. Infection with HIV, he says, eventually may be like having high blood pressure and diabetes -- diseases that are not curable, but that can be controlled.

The protease inhibitors in development are compounds that are absorbed by the body in varying degrees, with varied effectiveness and side effects. One problem with regimens of two or three AIDS drugs is expense. Many insurance companies and Medicaid won't pay for more than one drug.

Saquinavir will cost $5,800 wholesale for a year's supply; Roche Laboratories could not give a retail price. Financial assistance may be available, though. Call Hoffman-La Roche at (800) 526-6367 for information.

Saquinavir was approved by the FDA in just three months as part of an effort to speed the process for AIDS drugs. The government OK was based on the drug's effectiveness in laboratory measures, such as CD4 cell counts, rather than by other measures that would require a much longer period to monitor.

As part of the accelerated process, other protease inhibitors are being made available to a limited number of patients through lotteries run by drug makers. Information about a new lottery for 2,000 patients to take Abbott Laboratories' drug ritonavir is available by calling (800) 414-AIDS.

Initial studies on that drug were published in last week's New England Journal of Medicine.

Some researchers are concerned about a backlash and a loss of faith in the scientific process if some of these new drugs turn out to be less promising over time than early tests suggest.

"My fear is we're moving so fast in this disease sometimes, we don't have all the answers," Fischl says. "If we're going to do accelerated approval, patients and doctors have to realize that." Says FDA spokesman Arthur Whitmore: "Absolutely, positively, there's a trade-off. When you speed up things, you go with less data, and everyone knows that."
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