Researchers reported in the British medical journal The Lanceton Saturday that initial results of the longest, broadest trial ofthe anti-viral drug AZT to date showed, after three years offollow-up, no cumulative decrease in risk of death or diseaseprogression in individuals treated before symptoms of HIVinfection appear.
The study was intended to determine the value of earlytreatment with AZT, which has been recommended for patientswho have CD4-cell counts below 500 per millimeter blood,based on results from four smaller, shorter studies in the U.S.
The results, while not completely analyzed and presented, arenot terribly surprising, said Mark Jacobson, director of clinicalresearch of the AIDS Program at San Francisco General Hospitaland assistant professor of medicine at the University ofCalifornia, San Francisco.
"It reinforces that AZT therapy alone is inadequate," he said.AZT generally yields improved CD4 counts for about a year, hesaid, but as the disease progresses and HIV becomes resistantto AZT, also known as zidovudine, therapy is switched.
Since switching to newer drugs or combination therapies laterin the disease reflects the emerging practice, he said the studyis "a little bit anachronistic. ... We're looking forward, notbackward."
Added Paul Volberding, director of the AIDS program at SanFrancisco General Hospital, "While we know that AZT can helppatients in the short term, the real focus of AIDS clinicalresearch today is on developing other treatment strategies,such as sequential or combination therapies that are effectiveand well-tolerated over extended periods of time."
The randomized, double-blind study of 1,749 patients in theUnited Kingdom, Ireland and France involved giving 877patients 250 mg of AZT four times a day and 872 patientsplacebo. The protocol was modified in October 1989 to allowparticipants to begin AZT on the basis of at least two CD4counts of less than 500 one month apart.
Although treated patients showed an increase in CD4 cells afterthree months (a median change of +20 cells, compared to -10cells in the placebo group), authors Jean-Pierre Aboulker andAnn Marie Swart of the so-called "Concorde" trial said therewas no significant difference in clinical outcome. The three-year survival rate was 92 percent in the group that receivedimmediate treatment and 93 percent in the placebo group.
Most patients entering the trial, 912, had CD4 counts between200-500; 710 had counts above 500 (normal is 800-1,200) and103 had counts below 200.
Four previous trials with median follow-ups of one year foundearly treatment with AZT in certain patients can delay onset ofsevere disease, pointed out Daniel Hoth, director of the Divisionof AIDS at the National Institute of Allergy and InfectiousDiseases.
"At this time we see no basis for changing the currentrecommendation to initiate anti-retroviral therapy for HIV-infected persons whose CD4+ T cell count falls below 500 percubic millimeter of blood," he said.
AZT producer Burroughs Wellcome agreed, issuing a statementthat said in part, "The relevance of Concorde's final results tofuture clinical practice is ... likely to be limited," and pointed tointerest in combining treatment with such drugs as Bristol-Myers Squibb Co.'s ddI and Hoffmann-La Roche's ddC.
-- Nancy Garcia Associate Editor
(c) 1997 American Health Consultants. All rights reserved.