Few people are as blessed as Newton Butler. Despite the best efforts of researchers and caregivers, haft of all HIV-positive people develop AIDS within nine years of contracting the virus, and 40 percent die within that period. But last week, Butler’s life seemed a plausible picture of the future. As Magic Johnson prowled gracefully on the basketball court, five years after learning he was infected, researchers were unveiling some of the most promising clinical advances to date. Speaking at a weeklong scientific conference in Washington, the researchers showed that a new class of drugs called protease inhibitors can change the course of HIV disease, delaying both symptoms and death. Questions remain about how best to deploy the new drugs, and how to pay for them. But scientists and activists are elated. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, declares flatly: “These are the best drug findings we have had in the AIDS epidemic.”

HIV is a wily foe. Armed with special enzymes, it splices its own genes into the immune cells it infects, turning them into factories for producing more HIV (chart). Few AIDS researchers expect any drug to reverse the infection once it occurs; the goal is simply to make the virus less noxious, by foiling its efforts to reproduce within the body. The first signs of progress came in the mid-1980s, when researchers discovered that a failed cancer drug called AZT helped to keep HIV from integrating itself into host cells. In clinical studies, the drug reduced death rates among people with AIDS and delayed the onset of symptoms in those who were still healthy. But the benefits proved temporary. Because the virus mutates so rapidly within the body, it simply evades AZT after a year or two. Drugmakers have since come up with several agents (ddC, ddI, d4T and 3TC) that work on the same principle as AZT and can extend its effect when combined with it. But until recently, there was no stopping HIV once it had eluded this first line of defense.

That’s where the new protease inhibitors come in. Unlike AZT and its cousins, which help keep HIV out of the host cell’s chromosomes, these drugs help to keep successfully integrated HIV from reproducing at the cell’s expense (chart). The Food and Drug Administration approved the first protease inhibitor–Hoffmann-La Roche’s saquinavir–in December. Neither of the two drugs creating the buzz last week has been licensed for marketing. But both appear more potent than saquinavir, and both could win approval as early as next month.

The first, developed by Merck & Co., is called indinavir. In a study headed by Dr. Roy Gulick of New York University, doctors at four hospitals treated HIV-positive patients with indinavir, alone and in combination with two other drugs, for periods of four months. All the participants started with high levels of HIV in their blood, despite past treatment with AZT, but most responded dramatically to the new drug. After four months, 13 of 26 patients taking indinavir alone had no detectable virus in their blood, suggesting that the HIV in their cells had virtually stopped replicating. And 24 out of 26 patients combining indinavir with two other drugs (AZT and STC) achieved that result. The study was admittedly small and short-term, and it wasn’t designed to measure the treatment’s effect on the patients’ overall health. But experts say no other drug has shown such a striking ability to hold the virus in check.

The other new protease inhibitor, Abbott Laboratories’ ritonavir, is looking just as promising. In a large international study reported at last week’s meeting, 1,090 patients with severely compromised immune systems added either ritonavir or a placebo to whatever antivirals they were already taking. Researchers in 10 countries monitored the patients’ health and survival rates for seven months, and the results were dramatic. By the end of the study, 18 percent of the ritonavir patients had died or developed new AIDS-related illnesses, compared with 27 percent of the placebo patients. The mortality rate for ritonavir patients was 4.8 percent, just over half the 8.4 percent mortality in the placebo group.

Encouraging as they are, the new findings leave important questions unanswered. Because the studies were so brief, no one knows how long the new drugs’ effects will last. In the ritonavir study, patients’ vital levels climbed steadily after a sharp initial decline, suggesting that drug resistance was already setting in. If the protease inhibitors have long-lasting effects, then prolonged, early treatment will bring the greatest benefits. But if the drugs quickly lose their punch, it will make more sense to save them for later stages of infection. At the moment, no one knows which strategy is best–and since few patients want to postpone what may be a life-sustaining treatment, finding out could be difficult. “We’ve been here before,” says Fauci, recalling the early enthusiasm over AZT, “only to see years later we are finding real trouble.”

Even if their effects prove transient, the new drugs should improve patients’ prospects simply by creating more obstacles for the virus. “The medical tool kit is growing by leaps and bounds,” says Annette Ramirez, executive director of New York’s Hispanic AIDS Forum. If patients who exhausted one combination of drugs could always turn to another one, HIV infection might become a chronic but manageable condition, much like diabetes or kidney failure. The catch, of course, is that combination therapy can be breathtakingly expensive. The three-drug regimens now coming into vogue can cost $18,000 a year–and neither government programs nor private insurers are eager to absorb that shock. “We may have all these drugs approved,” says Moises Agosto of the National Minority. AIDS Council in Washington. “But if the programs can’t afford them, who’s going to have access?” Not the impoverished minority communities that are now at the center of the epidemic. “The new drugs are wonderful in terms of individual medicine,” says virologist June Osborne, who chaired the now defunct National Commission on AIDS. “But they have nothing to do with public health.”

Whatever their role, the new protease inhibitors aren’t the only signs that AIDS research is coming of age. The past few months have brought a spate of significant discoveries and innovations. In November Australian researchers identified the critical features of a naturally benign strain of HIV–a discovery that suggests new strategies for disabling the more aggressive strains now in wide circulation. In December German and American researchers identified several chemicals, produced by the body’s own cells, that can paralyze HIV in a culture dish. Dr. Robert Gallo, who led the U.S. team, predicts that combining such agents with other drugs will soon make AIDS “clinically curable.” Just weeks later, a 38-year-old AIDS patient named Jeff Getty checked into San Francisco General Hospital to have a baboon’s bone marrow pumped into his blood (baboons don’t get AIDS). In principle, the procedure could leave him with an immune system impervious to HIV.

No one pretends that the baboon procedure is anything but a gamble. But no one would deny that, like Magic Johnson, Getty embodies a new attitude toward HIV. Infected in 1980, he fell ill in ‘87 and says he has “almost bought it four or five times.” But he has aggressively sought out every new treatment in the book, from egg lipids to a three-drug combination including indinavir. And though he hasn’t had as smooth a ride as Newton Butler, he has managed to stay alive. “If you never do anything bold,” he says, “you never get any important answers.” We may not have them all yet, but the case for boldness gets stronger every day.

HIV turns infected cells into virus factories. Drugs that block specific reactions can foil the process, at least temporarily.

1 Virus attaches to receptors on a host cell, releasing its genetic material as RNA.

2 An enzyme converts the vital RNA into DNA.

Drugs called nucleoside analogues, such as AZT, can interrupt this process.

3 The viral DNA is integrated into the host cell’s chromosomes.

4 The infected cell produces new viral RNA, which generates proteins and other constituents of whole viruses.

5 The protease enzyme creates more proteins by cutting them into shorter pieces.

Protease inhibitors fight replication by neutralizing the enzyme.

6 The newly milled proteins fold together to form HIV capsules.

7 Completed HIV capsules break away to infect other cells.

SOURCE: MERCK & CO., INC.

PHOTO (COLOR): Bill T. Jones

THE POSITIVE OUTLOOK

HIV-INFECTED AMERICANS ON MAGIC, HEARTBREAK AND HOPE

Bill T. Jones, 43, dancer-choreographer, diagnosed HIV-positive in 1984. “When I tell someone I’m HIV-positive, I can see in their eyes that they feel sorry for me, that I’m already dead. And that makes me mad. When did I cross over?”

Bob Hattoy, 44, White House liaison for the Department of the Interior. Tested HIV-positive in 1988, diagnosed with AIDS in 1992. “The highs are that it’s allowed caring people to demonstrate their love to me. The lows are the amazing bigotry and stupidity. I’m glad Magic got to play again, but that’s not the reality of most people.”

Edmund White, 56, author. Diagnosed HIV-positive in 1985. “I do feel cautiously optimistic now [about the new drugs]. But some people will feel bitter regret that they lost lovers who could have been saved if they held on for two more years.”

Larry Kramer, 60, writer; founder of ACT UP; cofounder of Gay Men’s Health Crisis. Diagnosed HIV-positive in 1988. “I’m glad Magic’s playing again. But he made a lot of promises about how he’d be an advocate, and he has not been out there as a leader. Most of the sick people are people of color and can’t afford the drugs that Magic and I can afford.”

Bill Goldsworthy, 51, retired hockey player. Diagnosed with AIDS in 1994. “They look at you as if you’re either gay or use drugs. I’m not either. I have two lovely children, and I really worry about what people say.”

Mary Fisher, 47, activist and author. Diagnosed HIV-positive in 1991. “I’m hopeful about protease inhibitors, but I wouldn’t switch from what I’m on now. Magic’s coming back makes a statement. He’s playing ball, and I’m a mom. I can show my children what I do best.”

Greg Louganis, 36, diver. Diagnosed HIV-positive in 1988. “I knew it was ridiculous, but . . . I [felt] that I deserved to be HIV-positive. I was a faggot and this was the faggot’s punishment,” he writes in his book, “Breaking the Surface.” “[But now] I really feel like I’m starting life all over again.”