San Francisco Chronicle - The Voice of the West, 901 Mission Street, San Francisco, CA 94119 - Monday, March 10, 1997 -Page E1
Carl T. Hall, Chronicle Staff Writer

But even with their shortcomings, the newfangled pills known as protease inhibitors are about as close as you can get to a wonder drug for AIDS.

"People don't have to die anymore," said Dr. Mary Romeyn, a prominent San Francisco AIDS physician. "We're not just talking about buying a little more time. We're talking about the possibility of living out a full life-span -- of outliving your mother."

The protease inhibitors, which have been used for about two years, are carefully designed molecular monkey wrenches that doctors throw into the reproductive machinery of HIV, the virus that causes AIDS.

Protease is the common name for an enzyme the AIDS virus uses to reproduce itself. If the action of this enzyme is thwarted, the AIDS virus can't spread.

Different protease inhibitors have been introduced in rapid succession by some of the world's leading drug companies, including Roche, Merck & Co. and Glaxo Wellcome.

A powerful new protease inhibitor from San Diego-based Agouron Pharmaceutical Inc., called Viracept, is expected to gain Food and Drug Administration approval within a few weeks.

People who fail to show improvement using one drug often can get better results by switching to another. Some people are even taking two or more protease in- hibitors at once.

The protease inhibitors appear to be ineffective beyond a few months for about 10 percent of all cases in which they are tried.

The best results seem to come when the virus is hit hard and early. By trying different pills in different combinations, doctors hope to stay one step ahead as the deadly microbe tries to mutate into drug-resistant forms. By the same token, physicians warn that the pills can do more harm than good if people start and then stop taking them.

And the protease inhibitors only work effectively when used in combination with older AIDS medicines, such as AZT and 3TC. Those drugs act at different stages in the viral reproductive cycle.

The latest clinical evidence buttresses hundreds of individual tales of people bouncing back from the edge of death with the so-called triple-drug cocktails.

A government-sponsored nationwide study involving more than 1,000 people with HIV showed death rates were cut in half when people took Merck's protease inhibitor, Crixivan, along with AZT and 3TC, as compared with a control group of patients taking the two older drugs alone.

Previous studies had shown that a multidrug cocktail could reduce "viral load" -- the amount of virus circulating in the blood -- to undetectable levels, while allowing key measures of the body's natural disease-fighting system to recover. AIDS typically kills by wiping out the immune system, leaving the victim vulnerable to other infections.

"Now we have truly dramatic evidence of a clinical benefit from the triple combination," said Ron Baker, director of treatment and education at the San Francisco AIDS Foundation. "It really does have a payoff in terms of survival and disease progression."

It was so dramatic that the study was halted early so that people receiving the two-drug therapy could start getting a protease inhibitor. In fact, doctors at the front lines of the AIDS war in San Francisco refused to participate in the study at all, arguing it was unethical to subject patients in the two- drugs-only group to a therapy that they had already concluded was ineffective.

In the end, "it took very little follow-up to see what was happening," said Dr. Steven Deeks at San Francisco General Hospital. "It was just absolutely clear."

What is still uncertain is how long people will have to be on the heavy pill-popping regimens. Many experts hope that if infections are caught early on the virus essentially can be vanquished before it has a chance to really burrow in.

That might allow at least some people to be backed off the expensive new drugs, which can cost upwards of $15,000 to $20,000 a year.

This has inspired some tentative talk of a bona fide cure for newly infected people. But that's not expected to be in the cards for the vast majority of people with HIV, who instead face a lifetime battle to keep the virus from emerging out of its various hiding places.

For them, keeping HIV at bay would require constant vigilance and a full medicine cabinet for life.

This attitude toward AIDS has inspired a new race among the drug companies to design pills that are easier to take over a long period of time -- one or two pills per day instead of three or four; once- daily dosing rather than twice or three times a day; pills that can be taken without regard to when you have last eaten a meal and with fewer dangerous interactions with other medicines.

Within a few years, Baker said, the typical person with chronic HIV may have to simply take a few pills each morning and then forget about it until the next day.

"Protease inhibitors have given us all a new lease on life, including the drug companies," Baker said. "There's a lot more enthusiasm now for AIDS drug research."
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