Resistance to Drug Found in Tests of Some AIDS Patients
Scientists have detected resistance to the commonly used anti-AIDS drug AZT in blood samples drawn from a small number of AIDS patients who have received the medication for more than six months, it was announced Tuesday.
The laboratory findings of resistant strains of the AIDS virus--which researchers said were not unexpected--are likely to have no immediate effect on the use of AZT in AIDS patients. AZT was approved by the U.S. Food and Drug Administration in 1987 for many patients with either AIDS or advanced AIDS-related conditions.
But the new research, from the UC San Diego Medical Center and Wellcome Research Laboratories in Britain, is likely to stimulate efforts to design AIDS treatments that combine AZT with other medicines.
Previous research has suggested that AZT can prolong the lives of AIDS patients for an average of one to two years. AZT blocks the replication of HIV, the virus that causes AIDS, but does not rid the body of the infection. As a result, the immunodeficiency caused by HIV continues to progress.
AZT can also cause serious side effects, such as anemia, requiring discontinuation of the drug.
The new findings may also cause some physicians and patients to rethink the use of AZT in the early stages of infection with the human immunodeficiency virus. Although the benefit of AZT in the early stages of HIV infection has not been established, the antiviral drug is widely prescribed in this situation.
“I feel very strongly that no change in the management of individual (AIDS) patients should be based on these data,” Dr. Douglas Richman, a professor of pathology at UC San Diego, said. He expressed concern that misinterpretation of the findings would create inappropriate “fear or hysteria.”
Richman, one of three authors of the new study, said that resistance happens “with all drugs and all bugs and all tumor cells.” He said it was “not surprising” in the case of HIV. A germ is considered resistant when it develops the ability to grow in the presence of even high concentrations of a drug.
“So far, the resistance has not been proven to have clinical significance,” Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., told Associated Press.
“People who are on AZT and are currently benefiting from AZT should not panic and consider this a major setback,” Fauci said. “Just because one can isolate a resistant strain from a patient doesn’t mean AZT is not effective in combatting most of the viral replication in the patient.”
The early announcement of the findings, which are to be published in the journal Science on March 31, was made at press conferences in London and San Diego on Tuesday and in letters mailed by AZT’s manufacturer, Burroughs Wellcome Co. of Research Triangle Park, N.C., to AIDS physicians and infectious disease specialists around the country.
Regulators’ Demand
Kathy Bartlett, a spokeswoman for Burroughs Wellcome, said the results were being released by the company so that physicians could put them “in the proper context if questions came up from their patients.” But, according to Richman, “British regulatory agencies,” which oversee Wellcome PLC, the parent company for Burroughs Wellcome, had “demanded” the release.
Bartlett, Richman and Jeffrey L. Teramani, a spokesman for Science, all declined to make available a copy of the scientific paper. Many physicians consider it impossible to put findings into the proper context without reviewing the actual research report.
The new study involved 11 patients who had received AZT for more than six months, according to Monday’s “Dear Doctor” letter from Dr. S.W. Singleton, vice president of medical affairs for Burroughs Wellcome.
When samples of the patients’ blood were tested in the laboratory, many were of “reduced sensitivity,” including blood from five patients that had “very marked reductions in sensitivity,” the letter said. “Longer durations of treatment were associated with progressively less sensitive virus.”
More Studies Made
Richman said, “Some of the isolates were a hundredfold more resistant (than prior to AZT treatment).” He termed the findings a “pretty straightforward and consistent observation.”
Richman said studies are in progress to determine the mechanism of HIV resistance to AZT and to determine if asymptomatic HIV-infected individuals developed AZT resistance in a comparable fashion.
Singleton’s letter cautioned that “no correlations were evident” between the development of resistance to AZT in the laboratory and changes in the patients’ condition.
The letter said that, “Clinical decisions based on correlations between in vitro (test tube) sensitivities of virus and plasma concentrations of drug may be inappropriate and the clinical implications of these findings are therefore not clear.”
Burroughs Wellcome officials said that more than 20,000 people throughout the world are estimated to be taking AZT, which is also known as azidothymidine or zidovudine.
