An experimental antibiotic may prevent or delay the onset of a life-threatening and difficult-to-treat infection that afflicts thousands of AIDS patients, according to previously confidential data made available to The Times.
A recently completed study of 590 AIDS patients has shown that the drug, rifabutin, can nearly cut in half the rate at which patients develop the infection, which is known as Mycobacterium avium complex, or MAC.
"At this point, rifabutin appears to prevent or delay MAC infections in the bloodstream, which are a significant source of suffering in AIDS patients," said Beverley Wynne, the project leader for rifabutin at Adria Laboratories of Dublin, Ohio, which manufacturers the drug.
The advance could benefit many of the approximately 75,000 AIDS patients in the United States, most of whom have yet to develop a MAC infection of their bloodstream.
An effective preventive treatment for Mycobacterium avium complex would be "a major step forward," said Dr. Harry Hollander, an AIDS expert at UC San Francisco who was not involved in the research. "Over a quarter of the people (in the late stages of human immunodeficiency virus) disease are ultimately developing symptomatic MAC disease."
The U.S. Food and Drug Administration considered the preliminary data sufficiently compelling that on March 6 it authorized the pre-approval distribution of rifabutin to AIDS patients with severely impaired immune systems. Such patients are at greatest risk for developing the infection.
But there has been very little publicity about the FDA action, partly because the company, wishing to avoid the appearance of prematurely promoting the drug, has not released its favorable data. As a result, many AIDS patients and their physicians may be unaware of the new information and unable to benefit from it.
After an inquiry from The Times, officials of Adria Laboratories released some of their findings Tuesday. They said additional data from clinical trials of rifabutin will be presented Monday at a meeting in Washington of the federally funded AIDS Clinical Trials Group and at the international AIDS meeting in Amsterdam in July.
To prevent Mycobacterium avium complex, rifabutin is taken as two 150-milligram capsules a day, Wynne said. Wynne and Bethany A. Beck, a vice president of Adria Laboratories, said they expect that about 5,000 AIDS patients eventually will receive the drug through the expanded distribution program, which is known in FDA parlance as a treatment IND. As of the end of March, only 50 to 75 patients had been enrolled, officials said.
The FDA is considering an application from the company to allow prescription sales of the drug. A price has not been set.
MAC is common in patients who have had AIDS for several years, particularly those with very low levels of the CD4 cell in their blood stream. The CD4 cell is a key immune system cell that is attacked by the AIDS virus.
The bacteria that cause MAC, which are related to the germ that causes tuberculosis, are usually harmless to people with normal immune systems. But the Mycobacterium avium germs can wreak havoc in AIDS patients, causing fever, weight loss, fatigue, and abdominal problems.
Patients can become very sick when the infection spreads to the bloodstream, bone marrow, lymph nodes or liver. Treatment typically requires several drugs and is often unsuccessful. Side effects, such as abdominal problems, can be severe.
Rifabutin is related to rifampin, an antibiotic that is used to treat tuberculosis.
The company has recently completed two studies comparing rifabutin to a placebo capsule in patients with AIDS and fewer than 200 CD4 cells per cubic millimeter of blood. Both studies have been stopped and all participants placed on rifabutin because of "significant differences" favoring the use of the drug, Wynne said.
The first study began in February, 1990. As of November, 1991, 14.4% of the 298 patients receiving the placebo had developed MAC infections in their bloodstreams, compared to 8.2% of the 292 patients given rifabutin, a difference that was very significant, Wynne said. Even among the people who became infected, rifabutin appeared to significantly delay the development of the illness.
The second study, involving 556 AIDS patients, began in the Summer of 1990. Wynne said the results were "supportive" of the first study. But she declined to give details, saying the results were still being analyzed.
The most serious side effects associated with rifabutin appear to be low white blood-cell counts. Very few patients in the two studies had to discontinue the drug for this reason, Wynne said, adding, "This drug turned out to be remarkably safe."
Since the expanded distribution of AZT in 1986, it has become customary for AIDS researchers and companies sponsoring large AIDS clinical trials to release results in summary form when the federal government allows an experimental drug to be made widely available.
But Adria Laboratories has taken a low-profile approach. The researchers who conducted the MAC prevention trials had to sign confidentiality agreements prohibiting them from discussing the results, according to Beck.
When asked why, Beck said the company--a division of Erbamont Inc., a Montedison-Ferruzzi company--"did not want to be accused of promoting the drug before it was approved (for prescription sales) or making representations . . . which didn't turn out to be correct."
Physicians interested in enrolling their patients in the rifabutin treatment IND program can contact Adria Laboratories at 1-800-552-7228.