The Miami Herald, Inc.: Sunday, September 21, 1997
Stephen Smith, Herald Health Writer

And that could have profound implications for the course of the epidemic: Now, patients find it tough to adhere to regimens requiring them to gulp down dozens of pills several times a day. Patients who stop taking the medicines risk developing new, more virulent forms of the virus.

Using a metaphor from chess, Dr. David Ho told the 2,500 AIDS patients and activists gathered in Miami Beach for the U.S. Conference on AIDS that researchers have reached the endgame, or the final stage.

The combination drug therapies are enjoying wide success in making the virus undetectable in people's bloodstreams. Significantly, though, Ho reported that he and his colleagues have discovered tiny, dogged traces of virus in bits of lymph tissues, the very heart of the immune system.

"We still don't know whether it's feasible to eradicate HIV, mainly because we don't know if it's feasible to eradicate the last residual bit of virus," Ho told an audience that hailed him with gusto typically reserved for a rock star. "Where we are is sort of at the endgame, like a chess game. But the endgame could be as tough as any part of the game."

Ho, a New York virologist who was named Time Magazine's 1996 Man of the Year for his pioneering AIDS work, is credited with developing three-drug therapies that have reshaped the war on the epidemic.

Gone are days when a single drug, such as AZT, was the preferred course for patients. Today, if patients have the money or the private or public insurance to cover bills topping $15,000 a year, they take two older-generation medicines in combination with a drug from the newest, strongest category, protease inhibitors.

Timing essential

That means downing scores of pills, several times a day. And the timing can prove daunting: David Barr, the director of the Forum for Collaborative HIV Research, told an audience Saturday about his regime, which requires him not to eat two hours before or one hour after swallowing the drugs.

"Taking the pills wrong," Barr said, "can be worse than not taking them at all."

That's because taking them the wrong way allows development of strains of the virus resistant to any drugs now on the market. And that's why it has become a singular goal of pharmaceutical companies and researchers to develop drugs that aren't so demanding, drugs that won't spawn the side effects -- diarrhea, especially -- common with protease inhibitors.

Drug makers are developing protease drugs that would be taken once a day, and Ho believes that trials involving patients could begin within six months.

"In terms of once-a-day drugs, we see on the horizon several such candidates," Ho said at a press conference. "It would be great if we could come up with a triple- or quadruple-drug combination that the patient takes once in the morning or once in the evening and that's it.

"Then, I'll bet you the adherence rates will be much higher and the outcomes will be much better."

Declining deaths

Already, with the existing regimens, the outcomes have been impressive: In 1996, for the first time since the start of the epidemic, AIDS deaths declined nationwide.

Doctors have reported staggering decreases in blood-borne virus. In a small study of patients taking the drugs for more than two years, Ho reported no detectable HIV levels.

But scientists fretted that the virus, dreaded for its stealthy ways, could be lurking within the body. So Ho and his associates decided to extract lymph tissue and analyze its contents.

They found that about 99 percent of their samples showed no evidence of AIDS virus. But as they squinted at their microscopes, they would inevitably find a tiny, telling glow in at least one section of tissue from almost every patient that indicated the existence of a bit of virus.

Now, Ho is considering giving patients a vaccine, while continuing the drug therapies, that could protect them from the rogue pieces of virus.

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