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Circulating p24 Antigen Levels and Responses to Dideoxycytidine in Human Immunodeficiency Virus (HIV) Infections
A Phase I and II Study
- Thomas C. Merigan, MD;
- Gail Skowron, MD;
- Samuel A. Bozzette, MD;
- Douglas Richman, MD;
- Raj Uttamchandani, MD;
- Margaret Fischl, MD;
- Robert Schooley, MD;
- Martin Hirsch, MD;
- Whaijen Soo, MD, PhD;
- Carla Pettinelli, MD, PhD; and
- Herbert Schaumburg, MD
Abstract
Study Objective: To determine the safety and efficacy of dideoxycytidine in patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex.
Design: A partially randomized phase I and II outpatient, dose-ranging study.
Setting: Four university medical centers involving government-supported referral AIDS Clinical Trial Units.
Patients: Sixty-one patients with AIDS or advanced AIDS-related complex and 100 pg/mL or more serum p24 antigen titers.
Interventions: Dideoxycytidine was administered orally at 0. 06, 0.03, 0.01, or 0.005 mg/kg body weight every 4 hours for 3 to 6 months depending on tolerance and benefit.
Measurements and Main Results: In patients receiving 0. 06 and 0.03 mg/kg, diffuse erythematous rash, fever, and aphthous stomatitis occurred in the first weeks of therapy, but resolved later. Hematopoietic suppression was rare. Peripheral sensory neuropathy occurred in patients receiving 0.06 mg/kg and 0.03 mg/kg and improved after discontinuation of therapy. Serum p24 antigen fell significantly (P < 0.01) from baseline entry values in most of these patients. The CD4 lymphocytes rose transiently at the 0.03 mg/kg dosage. At the 0.005 mg/kg dosage, skin rash, fever, and aphthous stomatitis were mild or absent. Peripheral neuropathy, which occurred in all patients receiving 0.01 mg/kg was less severe than at higher dosages. At the 0.005 mg/kg dosage, peripheral neuropathy was occasionally seen. Significant suppression of serum p24 antigen was seen in most patients with AIDS-related complex receiving 0.01 mg/kg and less frequently in patients receiving 0.005 mg/kg.
Conclusions: Less toxic regimens of dideoxycytidine merit clinical assessment for advanced anti-human immunodeficiency virus-1 (HIV) infection. Several studies alternating dideoxycytidine and zidovudine are in progress.
Article and Author Information
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From Stanford University School of Medicine, Stanford; University of California, San Diego, California; University of Miami School of Medicine, Miami, Florida; and Harvard University, Boston, Massachusetts. For current author addresses, see end of text.
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Grant Support: All four institutions participating in this study are supported from cooperative group grants from the AIDS program of the National Institute of Allergy and Infectious Diseases.
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Requests for Reprints: Thomas C. Merigan, MD, Division of Infectious Diseases, S-156, Stanford University School of Medicine, Stanford, CA 94305.
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Current Author Addresses: Drs. Merigan and Skowron: Division of Infectious Diseases, S-156, Stanford University School of Medicine, Stanford, CA 94305.
Dr. Bozzette: UCSD Treatment Center, 3821 Fourth Avenue, H-208, San Diego, CA 92103.
Dr. Richman: Infectious Diseases, HlF, VA Medical Center, 3350 La Jolla Village Drive, San Diego, CA 92161.
Dr. Uttamchandani: University of Miami, Department of Medicine, D-90, P. O. Box 016960, Miami, FL 33101.
Dr. Fischl: University of Miami, Department of Medicine, R-60, P. O. Box 016960, Miami, FL 33101.
Drs. Schooley and Hirsch: Infectious Disease Unit, Massachusetts General Hospital, Boston, MA 02114.
Dr. Soo: Building 115, Room 587, Clinical Research and Development, Hoffmann La-Roche Inc., 340 Kinslnad Street, Nutley, NJ 07110.
Dr. Pettinelli: AIDS Program, National Institute of Allergies and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892.
Dr. Schaumburg: Albert Einstein College of Medicine, Department of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461.
- © 1989 American College of Physicians
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