Drugs Tried as Preventive AIDS Measure
WASHINGTON — Frustrated in their efforts to develop an AIDS vaccine, scientists have started to explore a wholly new approach to preventing the disease.
In animal and human experiments, drugs now used to treat acquired immune deficiency syndrome are instead being administered to keep the virus from taking hold in the body in the first place.
The idea is called chemoprevention. If this strategy proves successful, people would be given virus-fighting drugs immediately after exposure to the AIDS virus--or even before--to prevent infection and subsequent disease.
Scientists compare the approach to the use of chloroquine, a malaria-fighting drug, which is given to people visiting malaria-infested areas to prevent them from contracting the disease.
Both regimens involve using what is normally thought of as a treatment and turning it into a preventive measure--a sort of chemical vaccine.
Distinctions Become Blurred
“There are times when these distinctions blur,” said Dr. Samuel Broder of the National Cancer Institute, the first scientist to demonstrate the value of the drug AZT against AIDS.
Likely candidates for AIDS chemoprevention are emergency-room personnel and other health workers, who are regularly exposed to blood.
In early 1989, medical researchers plan to start a program with AIDS-infected pregnant women to see if chemoprevention can protect their infants from the virus.
“The ideal thing is to have a vaccine, no doubt about it,” said AIDS researcher William Haseltine of Harvard University. “But we don’t know when or if we’ll have a vaccine.” In fact, most experts believe that a traditional, polio-style vaccine against human immunodeficiency virus, if one is possible, is at least a decade away.
In September, a key federal AIDS policy steering panel identified chemoprevention as an area “strongly recommended for increased effort,” according to Dr. Daniel Hoth, director of the AIDS program at the National Institute of Allergy and Infectious Diseases. A formal proposal to boost research in this area is to be made next month.
Research Focuses on AZT
Most attention is focused on AZT, which was shown in 1986 to extend the lives of patients with advanced AIDS. Since then, AZT has been used earlier and earlier in the disease. Studies are already under way to see if AIDS symptoms can be prevented, or at least postponed, in people who are infected but still healthy.
In chemoprevention, treatment would take place before the patient developed AIDS antibodies, the sign of infection.
At Harvard, scientists have shown that AZT can prevent a virus similar to the human AIDS virus from gaining a foothold in mice. Experiments in monkeys have had similar results.
Dr. Ruth Ruprecht, one of the scientists who performed the mouse experiments, believes there is a window of time--probably several hours in the case of needle exposure, and possibly longer for sexual exposure--between the time the AIDS virus enters the body and the time its genes invade human cells, creating a permanent infection. If virus-killing drugs are already in the bloodstream at the time of exposure, or if they can be administered quickly enough, the experiments suggest, infection can be prevented.
“In my eyes, infection is reversible,” Ruprecht said, as long as viral genes have not entered human cells. It is possible to have “virus exposure without true infection.”
In experiments on monkeys, Harold McClure of Emory University in Atlanta has had similar success. McClure treated three of his 12 monkeys within an hour of AIDS exposure, and one did not develop an infection. It was surprising that even one monkey was apparently protected, McClure said, because he was using an especially potent form of monkey-AIDS virus that always causes infection and rapid death.
Monkey Tests Encouraging
Monkeys treated within 24 hours generally lived longer than those whose treatment began 72 hours after infection. McClure, who presented these results recently at a scientific conference in California, emphasized that the findings are preliminary.
In another project, researchers at Burroughs Wellcome Co., the firm that makes AZT, are trying to see if chemoprevention with AZT can protect lab technicians and health workers who accidentally stick themselves with AIDS-infected needles.
People who call the company’s hotline--1-800-HIV-STIK--are given a six-week course of either a placebo or of AZT. By late next year, Burroughs Wellcome scientists hope to have preliminary data showing whether rapid use of AZT prevents the virus from taking hold.
The study, however, has drawbacks. It is possible that only those lab workers with the most severe needle sticks--and thus the greatest fear of developing AIDS--enter the program. That would skew the results and make AZT appear less effective. What’s more, since only an estimated 1 in 200 needle sticks results in infection, it could take large numbers of cases to see if the treatment is having any significant effect. So far, only about 50 people have enrolled in the study.
Studies on Pregnant Women
In another human experiment, doctors at Columbia University in New York plan to begin treating pregnant AIDS carriers, in the last stages of pregnancy, with AZT in an effort to protect the fetus. Estimates vary, but many scientists believe about half of such babies ultimately develop AIDS. Ruprecht’s mouse experiments at Harvard have shown that AZT can cross the placenta and kill AIDS-like viruses in the fetus.
Doctors do not know when during pregnancy or birth AIDS infection occurs or why some infants become infected while others do not. But they do know the problem is growing, with some intravenous drug-using areas of New York and New Jersey reporting AIDS infection in one out of 60 births.
Widespread use of AZT in healthy people raises difficult policy questions because of the drug’s side effects. AZT can cause anemia and other changes to the bone marrow, usually after eight weeks of use.
In people at relatively high risk of getting AIDS--those stuck with needles, newborns of infected mothers and the spouses or lovers of infected people--the risk of potential side effects may be acceptable.
Safer Treatment Sought
But to use chemoprevention more extensively--some scientists, for example, envision a “morning-after pill” for use following a risky sexual encounter--a less-toxic treatment would have to be found.
As AIDS continues to spread--nearly 80,000 cases have been reported in the United States--directors of some hospital emergency rooms are enthusiastic about a drug to be given immediately after exposure. According to the Centers for Disease Control in Atlanta, 25 health-care workers around the world have become infected on the job, mostly from needle sticks. Such infections remain extremely rare, but hospital workers still worry.
“If I had a magic bullet, I could calm some of my nurses considerably,” said Dr. Douglas White, clinical director of Georgetown University Hospital’s emergency room. Staff members have quit Georgetown’s emergency room, he said, for fear of being exposed to AIDS-infected blood.
At the Johns Hopkins hospital emergency room in Baltimore, a study found 5.2% of patients to be AIDS carriers, according to Dr. Gabor Kelen, director of research. A drug treatment for exposed workers “would make people a little happier about work,” he said, “but may make people a little more lackadaisical in infection precautions, because they’d have something to fall back on, so exposures may go up.”
Drug Mixture Probable
As drug research continues, scientists hope to develop a drug mixture--probably AZT and one of several other anti-virals or immune-boosting drugs--that would be effective at lower doses.
Haseltine, the Harvard researcher who was one of the first to propose investigations into AIDS chemoprevention, thinks such a “drug cocktail” could be given before exposure to the virus in areas where AIDS is prevalent, such as parts of Africa or in some U.S. urban areas.
