The war on acquired immune deficiency syndrome has entered a new stage in which an array of experimental drugs that have begun to show positive effects against the disease will be tried in thousands of AIDS victims in coordinated tests across the United States.
While no successful treatment is certain to be found, the front in the AIDS battle is advancing from the laboratory, where the new drugs have been developed, into the hospitals and treatment centers of more than a half-dozen major American cities.
The new group of drugs being tested includes at least one that has given some hints of being able to retard the incessant and deadly progress of the AIDS virus in the body.
A half-dozen drugs now appear to be the best candidates for large-scale tests and a drug selection committee at the National Institutes of Health has begun choosing the most promising ones, setting aside those not up to standards.
"I'm hopeful," said Dr. Martin Hirsch of the Massachusetts General Hospital in Boston. "What is most hopeful is that there are six or eight different agents all showing positive activity in the lab, and they are all in various human trials now."
Dr. Paul Volberding of the University of California at San Francisco, one of the key research centers, said he was optimistic that something will be found to successfully combat AIDS.
But he cautioned that it is not possible yet to fix optimism on a single drug. "So far we have been too publicly optimistic, too soon," he said.
Dr. Samuel Broder, head of the clinical oncology program at the National Cancer Institute and chairman of the drug selection committee, said the large-scale testing of many drugs will allow researchers to make direct, detailed comparisons of what works and what doesn't, what is more toxic or less toxic. AIDS is caused by a virus that attacks the key cells of the body's immune system, rendering people defenseless to a variety of infectious diseases. AIDS, which has claimed 18,000 victims in the United States since 1981, appears to be virtually 100 percent fatal.
Among the several promising drugs, the one with the freshest results is Azidothymidine (AZT). It now appears that a substantial number of 19 AIDS patients in a trial of the drug for toxic effects were measurably improved. Toxic effects turned out to be moderate.
Fifteen of the 19 showed an increase in the number of "helper T cells," which are crucial to the functioning of the immune system. These cells are the main targets of the AIDS virus.
AIDS patients often fail to respond to tests to see if their immune systems can react to challenges. In six patients who failed to respond, the drug appeared to restore the system's ability to react as their T-cell levels rose. Most of the patients also gained weight and their spirits and appetites improved.
The drug does not eliminate the AIDS virus from the body. It merely prevents the virus from multiplying. It is hoped that retarding the virus will allow a victim's immune system to recover its strength.
AZT is one of a broader class of drugs being developed that attack the virus by gumming up its ability to multiply. It floods the cell with "false" building blocks that the virus uses to make copies of itself. Laboratory work has demonstrated that when the virus cannot make copies of itself, no further infection can take place.
One young woman, who was given AZT in early tests, said in an interview yesterday that "I know I am not cured, but the drug made me better . . . . I am in a completely different state than than I was," she said. The patient, Elizabeth B., asked that her identity not be divulged.
She said that when she started the drug test in October she was extremely weak and depressed and could not bathe or take care of herself. She had large sores in her mouth, and a severe infection that was causing her fingernails to rot and drop off, according to medical records. The conditions have cleared up and she is now strong enough to lead an active life again.
Instead of continuing to lose weight as AIDS victims do, the patient group as a whole gained an average of 5 pounds each during the six-week trial; the greatest gain was about 26 pounds.
In the patient group, six had detectable amounts of AIDS virus when they started on the drug; none was found in their systems by the end of the trial.
AZT is made by Burroughs Wellcome Co. of Research Triangle Park, N.C. The British medical journal Lancet is expected to publish the details of the AZT trials this week.
The tests were conducted by Dr. Broder and Robert Yarchoan at the National Cancer Institute, working with researchers at Duke University Medical Center, the University of Miami, and the University of California at Los Angeles.
Several other promising drugs work by similar mechanisms and could ultimately prove as good or better than AZT when all have been through their full cycle of tests. Some of the promising antiviral drugs being tested include Virazole (ribavirin), Foscarnet, Rifabutin (ansamycin), and a group of AZT-related drugs called "nucleoside analog" drugs.
AIDS continues to spread rapidly. It is estimated that between 1 million and 2 million people in the United States are infected and are carriers of the AIDS virus. Between 15 and 40 percent of those infected may get the disease, according to studies.
Though medicine has been able to find drugs to control bacteria, it has largely failed to find drugs that stop viruses. So far, viral diseases have been controlled by vaccines, not drugs. But even the most optimistic predicitions suggest that a vaccine for AIDS may not be available until the 1990s, if then.
Thus, hopes for an effective weapon against AIDS still rest with the risky and difficult effort to find a drug that attacks the virus without also destroying the cells that harbor the virus.
The drugs that finally prove useful will have to show a strong ability to stop the AIDS virus from multiplying, without strong toxic effects, according to criteria established by the NIH drug selection committee.
The drugs should also be capable of being taken orally, which is important because patients may have to take them daily for years. Because the virus can attack the brain, the drugs must be able to pass through the membrane system called the blood-brain barrier and enter the brain. They must also be capable of being manufactured on a large scale