Popular Drug for AIDS Seen as Ineffective

New scientific data indicates that oral dextran, one of the most popular underground AIDS remedies, is unlikely to be effective, The Times has learned.

Government AIDS scientists and some researchers have been aware of the data for more than a month but have made no public announcement, Dr. Frank E. Young, the commissioner of the U.S. Food and Drug Administration, said in an interview.

The experimental drug, which had been considered promising, is not significantly absorbed into the bloodstream, according to new human and animal studies. As a result, oral dextran is unlikely to protect infection-fighting white blood cells against the ravages of the human immunodeficiency virus, which is the cause of AIDS.

Young said the decision to remain silent reflected the “preliminary” nature of the results and his fears that an announcement might dash the hopes of thousands of HIV-infected individuals who are believed to be taking oral dextran.

But some AIDS physicians said it is important to get the new information out so that individuals who are taking the drug and their physicians can reassess the use of the medication.

Young confirmed Friday that the initial results of government-sponsored tests show that oral dextran “does not appear to be significantly absorbed” and “does not have the promise of effectiveness that a lot of people thought and that we hoped prior to having this information.”

Young said in a telephone interview that he “felt compelled to answer (The Times) honestly.” He said that patients “should really stay tuned for further information.”

Dr. Daniel Hoth, the director of the AIDS Program at the National Institute of Allergy and Infectious Diseases, cautioned that the data is preliminary and that it is “theoretically possible” that those who take the compound for many months can have “increased absorption of dextran over time.” But he acknowledged that “clinical pharmacologists have told me that there is not much precedent for this.”

Hoth added that officials at the institute and university researchers working with the drug are reviewing data from a six-month 60-patient study of oral dextran. That government-sponsored study, which began last August, is expected to help answer the lingering question about the absorption of oral dextran and provide new data about its effectiveness against HIV.

“I don’t think there is any great mystery about why there has been no announcement,” Hoth said. “We are dealing with scientific complexity, and we want to make sure that everything is pulled together before making a strong public statement.”

‘Harmful’ to Inject

Young also issued a strong warning to individuals who might now consider injecting the medication directly into the bloodstream. That “could be very, very harmful,” he said. When injected, dextran, a potent blood thinner, can cause bleeding, infections or severe allergic reactions.

Previous data has suggested that the oral dextran is unlikely to be harmful when taken by mouth, although it may cause gastrointestinal side-effects, such as bloating and diarrhea.

Dr. Michael S. Gottlieb, the Los Angeles AIDS physician who first described cases of the mysterious disease in 1981, said he tells his patients that they should “make up their own minds” about oral dextran but emphasizes that there is “no evidence” that the drug is absorbed.

“Most patients are enlightened enough to know that something that is not absorbed from their gastrointestinal tract is unlikely to benefit the widespread viral infection in their body,” said Gottlieb, who practices at Sherman Oaks Community Hospital.

Gottlieb added that the health establishment has a “duty” to make public early information about AIDS therapies that appear unlikely to be effective, like dextran, as well as therapies that appear beneficial, like AZT and aerosol pentamidine.

Once Considered Promising

Oral dextran had been considered a promising experimental therapy because of laboratory studies showing that the compound can both prevent the AIDS virus from infecting immune system cells in test tubes and interfere with the ability of the virus to kill these cells. The drug is manufactured by Ueno Fine Chemical Industry Ltd. of Osaka, Japan.

Over the last two years, HIV-infected individuals from across the country have organized “buyers’ clubs” that import the inexpensive drug from Japan, where it has been sold for many years without prescription as a treatment for atherosclerosis, or fatty collections in the arteries.

The buyers’ clubs make oral dextran available to people who want to purchase it for their own use. Some take the drug under the supervision of physicians and some use it surreptitiously, even while taking part in trials of other experimental agents.

Complaints from buyers’ clubs and other AIDS support organizations about difficulties in obtaining oral dextran prompted the FDA last summer to allow patients to legally import small quantities of unapproved medicines for personal use against AIDS and other diseases. These groups, however, have continued to criticize the FDA and the national institute for delays in initiating federal tests of oral dextran and other anti-AIDS drugs.

The new studies shedding doubt on the absorption of oral dextran involve six healthy human volunteers at Johns Hopkins Medical Center in Baltimore and FDA studies in laboratory rats. According to Young, they indicated that the “bioavailability (of dextran) by the oral route was essentially non-existent.”

Conference Call Report

The dose tested in humans--1,800 milligrams--is within the range of doses that AIDS patients have been administering to themselves.

These findings were shared among officials of the FDA, the national institute and AIDS investigators involved in other dextran studies in a conference telephone call on Jan. 11, Young said. Some people active in AIDS support organizations have been informally made aware of the findings.

The studies involved two techniques. First, FDA scientists attempted to directly measure the drug in the bloodstream of the rats by “high pressure liquid chromatography” but were unable to detect it, according to Young.

Second, a team of Johns Hopkins scientists used an indirect detection method that was considered even more sensitive by the FDA. This method took advantage of dextran’s ability, when injected directly into a vein, to interfere with the ability of the blood to clot.

When oral dextran was administered to the healthy volunteers as a single oral dose, no effect on blood clotting was found, Young said. By comparison, when dextran was administered intravenously to the volunteers in a lower dose, easily measurable blood thinning effects were observed. For this reason, AIDS researchers hope to begin studies of intravenous dextran.

San Francisco Study

Young said the FDA and Johns Hopkins findings also appear to be supported by a recent study of oral dextran at San Francisco General Hospital, conducted by a research team led by Dr. Donald I. Abrams.

The results of this eight-week, 34-patient study were published Feb. 1 in the Annals of Internal Medicine. The study found that the patients’ blood clotted just as quickly when they received the highest doses of oral dextran (5,400 milligrams a day) as it did when no dextran was administered.

Abrams, who is also the principal investigator for the ongoing 60-patient dextran study, could not be reached for comment on the new data.

Scientists are uncertain why dextran appears not to be absorbed. One possibility is that a coating, which protects the drug from destructive stomach acids, interferes with absorption through the intestine. Another is that the drug is degraded by enzymes in the intestine. Still another possible explanation may be related to the large size of the molecule.

Dextran is the generic name for a family of large “polysaccharide” molecules that contain both glucose and sulfur. The dextran being tested against AIDS has a “molecular weight” of 7,000 to 8,000 daltons. By comparison, AZT, or azidothymidine, the oral antiviral drug that has been shown to prolong the life of some AIDS patients, has a molecular weight of only 267 daltons.