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Previous Volume 336:1704-1712 June 12, 1997 Number 24 Next

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ABSTRACT

Background Zidovudine has been the drug of choice for the initial treatment of symptomatic children infected with the human immunodeficiency virus (HIV). This trial was designed to assess the efficacy and safety of treatment with zidovudine alone as compared with either didanosine alone or combination therapy with zidovudine plus didanosine.

Methods In this multicenter, double-blind study, symptomatic HIV-infected children 3 months through 18 years of age were stratified according to age (<30 months or >30 months) and randomly assigned to receive zidovudine, didanosine, or zidovudine plus didanosine. The primary end point was length of time to death or to progression of HIV disease.

Results Of the 831 children who could be evaluated, 92 percent had never received antiretroviral therapy and 90 percent had acquired HIV perinatally. An interim analysis (median follow-up, 23 months) showed a significantly higher risk of HIV-disease progression or death in patients receiving zidovudine alone than in those receiving combination therapy (relative risk, 0.61; 95 percent confidence interval, 0.42 to 0.88; P = 0.007). The study arm with zidovudine alone was stopped and unblinded; the other two treatment arms were continued. At the end of the study, didanosine alone had an efficacy similar to that of zidovudine plus didanosine (median follow-up, 32 months) (relative risk of disease progression or death, 0.98; 95 percent confidence interval, 0.70 to 1.37; P = 0.91). A significantly lower risk of anemia or neutropenia was seen in patients receiving didanosine alone (P = 0.036).

Conclusions In symptomatic HIV-infected children, treatment with either didanosine alone or zidovudine plus didanosine was more effective than treatment with zidovudine alone. The efficacy of didanosine alone was similar to that of the combination therapy and was associated with less hematologic toxicity.

Source Information

From the Departments of Pediatrics and of Microbiology and Immunology, Baylor College of Medicine, Houston (J.A.E., C.J.B.); the Department of Biostatistics, Harvard School of Public Health, Boston (C.R.); the Department of Pediatrics, Duke University School of Medicine, Durham, N.C. (R.E.M.); Frontier Science and Technology Research Foundation, Amherst, N.Y. (B.P.); the National Institute of Allergy and Infectious Diseases, Bethesda, Md. (M.G.F.); the Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center, Houston (D.P.); the Department of Pediatrics, Columbia University, New York (A.G.); the Department of Pediatrics, Children's Hospital of New Jersey, Newark (G.D.M.); the Department of Pediatrics, Harlem Hospital, New York (E.J.A.); the Department of Pediatrics, Albert Einstein College of Medicine, New York (J.S.); and the Department of Pediatrics, University of Massachusetts, Amherst (J.L.S.). Other authors were Rachel Behrman, M.D. (Food and Drug Administration, Kensington, Md.), James C. Connor, M.D. (University of California, San Diego), Seth Hetherington, M.D. (Glaxo–Wellcome Pharmaceuticals, Research Triangle Park, N.C.), Marta H. Lifschitz, M.D. (Baylor College of Medicine, Houston) (deceased), Colin McLaren, Ph.D. (Bristol-Myers Squibb Pharmaceuticals, Wallingford, Conn.), Herman Mendez, M.D. (State University of New York Health Science Center, Brooklyn), Karen Millison, B.S., Clinical Trials Specialist (ACTG Operations Office, Bethesda, Md.), Jack Moye, M.D. (Pediatric and Adolescent Branch, National Institute of Child Health and Human Development, Bethesda, Md.), Molly Nozyce, Ph.D. (Bronx Lebanon Hospital, New York), Karen O'Donnell, Ph.D. (Duke University School of Medicine, Durham, N.C.), Lynette Purdue, Pharm.D. (National Institute of Allergy and Infectious Diseases, Bethesda, Md.), David Schoenfeld, Ph.D. (Harvard School of Public Health, Boston), Gwendolynn Scott, M.D. (University of Miami School of Medicine, Miami), Stephen A. Spector, M.D. (University of California, San Diego), and Diane W. Wara, M.D. (University of California, San Francisco).

Address reprint requests to Dr. Englund at the Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030.

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