Good news about AIDS can be a scary thing. When good news is heard, people who have tracked the twists in this 15-year-old epidemic swallow hard, then brace for letdown.
But 1996 has been a buoyant time on the AIDS front. Suddenly, doctors and advocates are daring to use phrases like "new era." At the heart of their enthusiasm is a series of new drugs -- most of them belonging to a class called "protease inhibitors" -- that appear more powerful than any AIDS medications previously developed.
Recent studies have shown that protease inhibitors can greatly reduce concentrations of the human immunodeficiency virus -- HIV -- floating in a person's bloodstream. This means less virus crippling the immune system and, consequently, more white blood cells to quell the infections that ultimately kill people with AIDS.
The drugs are not used alone but in combinations with older medications such as AZT or DDi. These "cocktails" have produced remarkable results in the short run, the sort of findings that usually provoke expectations of failure in the long run. The disease is so tenacious that early success has often been a prelude to failure.
But scientists are daring to voice optimism.
"Patients put on weight; they feel great. It's really wonderful," says Dr. Steven Schnittman, assistant director for clinical research at the National Institutes of Health's Division of AIDS.
Just listen to Martin Delaney, a long-term critic of the AIDS research establishment who heads Project Inform, a San Francisco-based patient advocacy group: "It's clearly a threshold we've never been at before. What the long-term effect is, we don't know. But they are a real order of magnitude more potent."
The new drugs work by inhibiting an enzyme that is critical to viral replication. This is important because HIV kills by infecting TC white blood cells, then turning those cells into factories that make more virus. It's an insidious spiral that ultimately destroys the immune system and, with it, a person's ability to defend against all types of infection.
Drugs such as AZT belong to a different class called nucleoside analogues. They interfere with viral replication, too, but at an earlier stage in HIV's life cycle. Patients combining two of the drugs can attack the virus from two different angles -- a strategy that might enable them to outmaneuver the virus for years.
At least that's the hope.
So far, in studies that have lasted less than a year, patients taking the regimens are dying at a much slower pace than did patients taking old-line drugs alone. Why?
First, the combinations are drastically reducing "viral load" -- the number of virus particles that can be measured in a quantity of blood. Taken individually, drugs like AZT can cause viral load to drop to a third of its previous level. Protease inhibitors can cut viral load to one-hundredth.
But when the old and new drugs are combined, the results are startling: as little as one-thousandth of the amount of free-floating HIV.
Patients have also made dramatic gains in another index of health -- their CD4 counts. This is the index of disease-fighting white blood cells that are ordinarily devastated by the AIDS virus.
What this means for a patient's long-term survival is unclear. Longer studies will answer that question.
Nobody, however, is expecting a cure -- just prolongation of life. Although patients can harbor the HIV for 10 years or longer before progressing to the full-blown disease, they usually die within two years after reaching the AIDS threshold. (Some patients live longer, though nobody knows why.)
One goal would be to extend survival so long that patients could simply live out their lives holding the virus at bay with a variety of drugs. At that point, AIDS (acquired immune deficiency syndrome) would become a chronic disease like diabetes, effectively managed without ever going away.
"We're not at that point yet, but with these drugs we are a lot closer than we ever were," says Dr. Richard Chaisson, director of the B. Frank Polk AIDS Unit at the Johns Hopkins Hospital.
But as doctors look for the best ways to use the drugs, they are drawing an analogy to another disease: tuberculosis.
From the 1920s into the 1940s, researchers searched for antibiotics capable of destroying the bacteria that cause the deadly respiratory disease. Finally, in the mid-1940s, doctors rejoiced when they were given streptomycin -- a drug that proved amazingly effective. A Nobel Prize was awarded to Selman Waksman, a biologist at Rutgers University who discovered the miracle agent in soil. People got better. The battle seemed won.
But jubilation gave way to disappointment. Many people relapsed into TB. The drug killed most of the bacteria, but not resistant strains that soon multiplied until the disease raged again. Eventually, doctors discovered that they could outfox the bacteria with combinations of two or more antibiotics.
The logic was simple. Bacteria that resisted one drug succumbed to another. Today, patients who faithfully take all their all their medications for six months are generally cured. Those who don't can relapse with nasty strains.
AIDS drug combinations have come into vogue not just because they assault the virus from different angles, but because they fight resistance in much the same manner as the TB drugs. But there is a crucial difference.
"The difference is that TB can be cured with a given duration of treatment," Dr. Chaisson said. "We can actually get rid of all the bugs in the body. Thus far, with HIV we can't do that."
For now, doctors are assuming that people will become resistant to the cocktails, too -- eventually. The goal is to squeeze maximum potency, in part by finding the combinations and dosing schedules that forestall resistance the longest.
Doctors are debating whether to give the drugs early or late in the disease progression. Give them early and a patient might live a relatively healthy life for many years, free of the crippling infections that are common in AIDS' late stages. Give them late and the patient is armed when times are worst.
Whenever they are given, the drugs will be expensive. Insurance companies that now spend $5,000 to $7,000 annually per patient for AIDS drugs will be paying twice that. Maryland and a handful of other states have budgeted more money to provide new drugs to the uninsured. But pharmacy assistance programs in other states are facing cutbacks -- not increases.
In the meantime, groups like Project Inform and the National Minority AIDS Council are urging patients to take the new drugs exactly as ordered -- to refrain from the self-experimentation that has been a common feature in this epidemic.
"If they don't use them right, they'll just get a short-term boost," Mr. Delaney says. "I think it's going to take some retraining."
For now, AIDS remains the supreme challenge. Doctors can quash bacterial diseases with antibiotics, but they do not have equally effective drugs to kill viruses. The immune system is a person's best defense, but AIDS renders that helpless.
"Other viral diseases we're used to -- measles, chicken pox, influenza -- come along and either kill you, or you get sick and get better," Dr. Chaisson said. "This is an infection that gets established and destroys the immune system over a period of years. It's an entirely new type of disease."
Pub Date: 4/21/96