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ACTG 116B/117: High Levels of AZT Resistance May Predict HIV Disease Progression

Date: June 8, 1993
Source: National Institutes of Health (NIH)
Author: National Institute of Allergy and Infectious Diseases (NIAID)

Patients carrying strains of HIV highly resistant to the drug zidovudine (AZT) may be more likely than those with less-resistant strains to develop new HIV-related symptoms, according to a supplemental analysis of an AIDS clinical trial supported by the National Institute of Allergy and Infectious Diseases.

Victoria A. Johnson, M.D., of the University of Alabama at Birmingham plans to present preliminary data from the analysis in a poster at the IXth International Conference on AIDS in Berlin on June 8.

The researchers found that patients who had entered the since-completed clinical trial with HIV strains highly resistant to AZT were 2.9 times more likely to die or suffer new HIV-related symptoms than those with AZT-sensitive strains. Patients with moderate levels of resistance had 1.6 times the risk of dying or suffering new HIV-related symptoms. In the clinical trial, known as AIDS Clinical Trials Group (ACTG) 116b/117, all of the patients had advanced HIV disease and had taken AZT for at least 16 weeks.

For the current analysis, which is ongoing, the study investigators have tested 145 samples of HIV derived from blood drawn from patients at study entry. The researchers have observed AZT resistance in 56 (39 percent) of these samples, and high levels of resistance in an additional 22 samples (15 percent).

ACTG 116B/117 compared the safety and effectiveness of AZT and didanosine (ddI) in patients with advanced disease who had taken and tolerated AZT for at least 16 weeks. The study demonstrated that switching to 500 milligrams of ddI daily was more effective than continued AZT therapy in slowing the progression of HIV disease in certain patients. These results appeared in the August 27, 1992 New England Journal of Medicine.

The investigators conclude that the beneficial effects of switching to ddI reported last year cannot be explained by ddI's effectiveness against AZT-resistant strains of HIV because they observed an increased risk of disease progression associated with AZT resistance among patients receiving AZT and those receiving ddI.

The implication of the results of the resistance analysis for the clinical management of patients remains unclear," says x. "Further clinical and laboratory investigation will be necessary to define how best to use results of drug susceptibility tests."

Another study, ACTG 194, is investigating AZT resistance in persons who have taken AZT for a year or more and have not taken other antiretroviral drugs. This study will provide information on the clinical significance of AZT resistance for individuals on long-term AZT therapy.

The ACTG is a nationwide network of AIDS clinical research centers funded by NIAID that conducts studies to evaluate the safety of new drugs, drug combinations and vaccines in adults and children at various stages of HIV disease.

NIAID, a component of the National Institutes of Health, supports research on allergies, immunology and infectious diseases. NIH is an agency of the U.S. Public Health Service, part of the U.S. Department of Health and Human Services.

"HIV-1 drug resistance and syncytium-inducing phenotype: Associations with disease progression among ACTG 116B/117 subjects." Victoria A. Johnson, M.D., University of Alabama at Birmingham; Richard T. D'Aquila, M.D., Harvard Medical School and Massachusetts General Hospital; Dan Kuritzkes, M.D., University of Colorado, Denver; Anthony Japour, M.D., and Clyde S. Crumpacker, M.D., Harvard Medical School and Beth Israel Hospital, Boston; Douglas D. Richman, M.D., University of California, San Diego, et. al. for the NIAID AIDS Clinical Trials Group Virology Committee Working Group and the ACTG Protocol 116B/117 Team.

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