A Randomized Controlled Trial of a Reduced Daily Dose of Zidovudine in Patients with the Acquired Immunodeficiency Syndrome

作者：Margaret A. Fischl, Corette B. Parker, Carla Pettinelli, Michael S. Wulfsohn, Martin Hirsch, Ann C. Collier, Diana Antoniskis, Monto Ho, Douglas D. Richman, Edward J. Fuchs, Thomas C. Merigan, Richard C. Reichman, JONATHAN W. M. GOLD, Neal H. Steigbigel, Gifford S. Leoung, Suraiya Rasheed, Anastasios A. Tsiatis · 发表于：New England Journal of Medicine · 年份：1990 · DOI：10.1056/nejm199010113231501 · 被引用次数：325 · 研究领域：Pneumocystis jirovecii pneumonia detection and treatment、HIV/AIDS drug development and treatment、Pneumonia and Respiratory Infections

BACKGROUND: The initially tested dose of zidovudine for the treatment of patients with advanced disease caused by the human immunodeficiency virus type 1 (HIV) was 1500 mg. Although this dose is effective, it is associated with substantial toxicity. METHODS: To evaluate the efficacy and safety of a reduced dose, we conducted a randomized controlled trial in 524 subjects who had had a first episode of Pneumocystis carinii pneumonia. The subjects were assigned to receive zidovudine in either a dose of 250 mg taken orally every four hours (the standard-treatment group, n = 262) or a dose of 200 mg taken orally every four hours for four weeks and thereafter 100 mg taken every four hours (the low-dose group, n = 262). RESULTS: The median length of follow-up was 25.6 months. At 18 months the estimated survival rates were 52 percent for the standard-treatment group and 63 percent for the low-dose group (P = 0.012 by the log-rank test). At 24 months the estimated survival rates were 27 percent for the standard-treatment group and 34 percent for the low-dose group (P = 0.033). In both groups, 82 percent of the subjects had another opportunistic infection, and the length of time to that infection was similar in the two groups (P = 0.56 by the log-rank test). CD4 T-lymphocyte counts improved transiently in both groups, and serum levels of HIV antigen decreased in the subjects with antigenemia. The hemoglobin level declined to less than 5 mmol per liter (80 g per liter) in 101 subjects i...