Science / Medicine : New...
The recent decision by the National Institutes of Health to offer the drug AZT to employees with “significant” occupational exposures to the AIDS virus has raised questions about how and when the drug should be used. Some AIDS specialists fear that the NIH recommendation may be misinterpreted as a call for indiscriminate use of an expensive and potentially toxic drug.
AZT has been used primarily as a treatment for AIDS-infected individuals who have developed acquired immune deficiency syndrome or other evidence of severe immune deficiency. The drug, which is manufactured by Burroughs Wellcome Co. of Research Triangle Park, N.C., blocks the replication of the human immunodeficiency virus, the cause of AIDS, but does not rid the body of HIV infection.
Leading AIDS physicians said the NIH decision to offer AZT as a preventive treatment for uninfected individuals was simply a recommendation for “case by case” decisions about a relatively unusual circumstance, such as accidental needle sticks. They said the NIH policy, announced Feb. 25, should not be seen as an endorsement of other unproven uses of the antiviral pill outside of experimental trials.
The implications of the decision for other clinical situations “should really be quite limited,” said Dr. Harry Hollander, chief AIDS physician at UC Medical Center, San Francisco. “This is a unique situation where you know the exact time of exposure to the virus. . . . Personally, I think you are on very dangerous ground extrapolating any further.”
Dr. Richard Chaisson, director of the AIDS service at Johns Hopkins Hospital in Baltimore, said there were “a lot of troubling questions about the prophylactic use of AZT,” such as the possibility of “long-term toxicity following even short-term exposure.”
Chaisson said one possible use of AZT, as a “morning-after” pill for an uninfected person who has had sexual intercourse with an infected individual, “is really stretching things a lot.” He cited the difficulty of defining a “significant” sexual exposure to the virus and the lack of generally accepted data defining the risk of HIV infection from a single or multiple episodes of sexual intercourse.
Other physicians also cautioned that excessive use of AZT could create more problems than it would solve. The drug can cause severe anemia, requiring blood transfusions or discontinuation of the medicine. AZT can also cause nausea, muscle aches and sleeplessness. Long-term toxicities, including the risk of cancer or birth defects, are unknown.
Dr. Paul Volberding of San Francisco General Hospital said the most important message from the NIH action was the need for all medical centers to have a knowledgeable physician available at all times to give “an immediate assessment of risk” to health-care workers who may be exposed to HIV. At San Francisco General, an assigned physician carries a “needle-stick beeper” and gives such advice.
As a result, the decision about the use of AZT can be reached quickly, preferably within hours after the exposure. “There is general belief that if AZT is going to have any value, the sooner you take it the better,” said Volberding, who was a consultant to the NIH committee that developed the new policy.
In 1987, the U.S. Food and Drug Administration approved prescription sales of AZT, which is also known as azidothymidine or zidovudine.
AZT has not been shown to prevent the development of AIDS in HIV-infected individuals who are not ill or to prevent HIV-infection in uninfected individuals who are exposed to the virus. The fact that a drug works at one stage of a disease--for example, in the advanced stages of HIV infection--does not mean that it will necessarily work at another stage of the disease, such as to prevent infection or in the early stages of infection. Human and animal tests of AZT in these situations are in progress.
But once a drug is approved for marketing by the FDA, physicians are free to prescribe it as they wish. As a result, physicians, exercising what in medical parlance is known as “clinical judgment,” often prescribe drugs for reasons that are not covered in the FDA-approved drug labeling or validated in rigorous clinical tests.
Even in the absence of good data, some physicians who care for AIDS patients say AZT should be prescribed early on in the course of HIV-infection, given the progressive and ultimately fatal nature of AIDS.
AIDS patients commonly take AZT every four hours around-the-clock for an indefinite period. Health-care workers with HIV exposure are prescribed AZT in a similar fashion, usually for a period of six weeks.
When a health-care worker sustains a “significant” exposure to HIV, the risk of becoming infected is about one in 250, according to Dr. Henry Masur, chief of the critical care medicine department at the NIH and chairman of the committee that recommended the institutes’ new policy.
The distinction between “significant” and “insignificant” exposures is somewhat arbitrary. Most AIDS specialists believe that a deep needle-stick injury into a muscle or the accidental injection into body tissues of blood or laboratory solutions containing HIV are very significant. But a situation, for instance, where a HIV-contaminated needle grazes the skin but does not draw blood may not pose as serious a risk.
The new NIH policy has evolved over the last six months, Masur said. Previously, the institutes, the research arm of the federal government, had recommended that their employees consider participating in a Burroughs Wellcome study, in which some HIV-exposed health-care workers receive AZT and others receive a placebo. A spokeswoman for the company said there are no plans to discontinue the study, which has enrolled about 70 individuals since last May.
According to Masur, NIH officials have become convinced that the Burroughs Wellcome study is unlikely to provide a definitive answer, one way or the other, about the role of AZT in preventing HIV infections. In addition, he said there are “very preliminary” studies in mice which suggest that AZT can prevent these rodents from becoming infected with a mouse virus that has similarities to the AIDS virus.
“We are dealing with a situation where honest people have to admit that they have very little data,” Masur said. “We have decided that we must do something and (offering AZT) is the most reasonable course of action in February, 1989.”
Masur acknowledged that “this may not be the correct course,” adding that “other well-informed people may make a different decision because we are all groping in the dark.” Masur said his committee will review its recommendations in April.
At present, about 15 to 30 NIH employees a year have significant exposures to HIV. In recent months, about half have “elected to go on AZT,” a percentage Masur said was “not expected to change” with the new policy.
One of the AIDS specialists who takes a more cautious view is UCSF’s Hollander. He urged physicians to “learn as much as possible” about the specifics of each possible HIV exposure and not simply prescribe AZT for “all health-care workers who believe they have had a significant contact.” Hollander predicted that broad prescription of AZT in such situations would “lead to a great deal of unnecessary cost” and eventually “demonstrate that there are toxicities of this therapy even in healthy adults.”
