The National Institute of Allergy and Infectious Disease (NIAID) has opened a trial for HIV-infected people to compare combinations of Zidovudine (AZT), Zalcitabine (ddC) and Ro 31-8959, an experimental drug that inhibits an enzyme HIV needs to reproduce.
The Phase II trial is the first U.S. study to examine Ro 31-8959. Made by Hoffmann-LaRoche Inc., Ro 31-8959 previously has been studied in Phase I and II trials in Europe, which found no significant side effects when the drug was given alone or in combination with AZT. In the NIAID trial, investigators at 10 sites of the AIDS Clinical Trial Group network will evaluate the combination therapies for safety, tolerance and immune system response.
This trial will further extend out knowledge of Ro 31-8959 as an HIV therapy," says Anthony S. Fauci, M.D., director of NIAID. "Using this drug to target and interfere with a particular aspect of HIV's life cycle may lead to a more effective and safer therapy for HIV disease."
Ro 31-8959 interferes with the activity of the protease enzyme that HIV uses to separate large proteins into smaller parts that are needed to make new copies of virus. If the proteins are not cleaved by protease, new virus still is assembled, but it cannot function properly or cause infection.
During the study, 300 participants will be assigned at random to take one of three combinations: Ro 31-8959 and AZT; AZT and ddC; or Ro 31-8959, AZT and ddC. Of the three drugs, only AZT is approved by the Food and Drug Administration as a single therapy for HIV infection. The FDA has approved ddC, but only for use in combination with AZT.
To enroll, participants must be HIV infected and have counts of the immune system cell, CD4+ T, of between 300 and 50 per cubic milliliter of blood (mm3). A healthy uninfected adult has 800 to 1,200/mm3 of such cells. All participants must have taken a minimum dose of 500 milligrams AZT a day for at least four months without any serious side effects.
Participants will receive one combination for 24 weeks. Investigators will measure CD4+ T cell responses and the amount of virus present in each participant's peripheral blood.
The 10 sites for the trial, ACTG #229, are: New York University Medical Center, N.Y.; Northwestern University School of Medicine, Chicago, Ill,; Ohio State University Hospitals, Columbus; Stanford University Medical Center, Calif.; University of Alabama at Birmingham; University of Colorado Health Sciences Center, Denver; University of Pennsylvania, Philadelphia; University of Rochester Medical Center, N.Y.; University of Texas at Galveston; and University of Washington, Seattle.
Ann C. Collier, M.D., chairs the study and Lawrence Corey, M.D., serves as co-chair. Both are the University of Washington.
NIAID, a component of the National Institutes of Health (NIH), supports research on allergy, immunology and infectious disease. NIH is an agency of the U.S. Public Health Service, Department of Health and Human Services.
For more information about this or other trials, call the AIDS Clinical Trials Service at 1-800-Trials-A from 9 a.m. to 7 p.m., EST.