FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

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

	Full Text PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

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.

Full Text of this Article

This article has been cited by other articles:

• Rajasekaran, S., Jeyaseelan, L., Ravichandran, N, Gomathi, C., Thara, F., Chandrasekar, C. (2008). Efficacy of Antiretroviral Therapy Program in Children in India: Prognostic Factors and Survival Analysis. J Trop Pediatr 0: fmm073v1-fmm073 [Abstract] [Full Text]  
• (2005). Additional Information. JAMA 294: E1-E3 [Full Text]  
• Berk, D. R., Falkovitz-Halpern, M. S., Hill, D. W., Albin, C., Arrieta, A., Bork, J. M., Cohan, D., Nilson, B., Petru, A., Ruiz, J., Weintrub, P. S., Wenman, W., Maldonado, Y. A., for the California Pediatric HIV Study Group, (2005). Temporal Trends in Early Clinical Manifestations of Perinatal HIV Infection in a Population-Based Cohort. JAMA 293: 2221-2231 [Abstract] [Full Text]  
• Jeremy, R. J., Kim, S., Nozyce, M., Nachman, S., McIntosh, K., Pelton, S. I., Yogev, R., Wiznia, A., Johnson, G. M., Krogstad, P., Stanley, K., for the Pediatric AIDS Clinical Trials Group 338, (2005). Neuropsychological Functioning and Viral Load in Stable Antiretroviral Therapy-Experienced HIV-Infected Children. Pediatrics 115: 380-387 [Abstract] [Full Text]  
• Ioannidis, J. P.A., Evans, S. J.W., Gotzsche, P. C., O'Neill, R. T., Altman, D. G., Schulz, K., Moher, D., for the CONSORT Group*, (2004). Better Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement. ANN INTERN MED 141: 781-788 [Abstract] [Full Text]  
• Capparelli, E. V., Englund, J. A., Connor, J. D., Spector, S. A., McKinney, R. E., Palumbo, P., Baker, C. J., the PACTG 152 Team, (2003). Population Pharmacokinetics and Pharmacodynamics of Zidovudine in HIV-Infected Infants and Children. J Clin Pharmacol 43: 133-140 [Abstract] [Full Text]  
• Cooper, D. A. (2002). Update on Didanosine. J Int Assoc Physicians AIDS Care (Chic Ill) 1: 15-25 [Abstract]  
• (2001). Five year follow up of vertically HIV infected children in a randomised double blind controlled trial of immediate versus deferred zidovudine: the PENTA 1 trial. Arch. Dis. Child. 84: 230-236 [Abstract] [Full Text]  
• Sáez-Llorens, X., Nelson Jr, R. P., Emmanuel, P., Wiznia, A., Mitchell, C., Church, J. A., Sleasman, J., Van Dyke, R., Richardson, C. G., Cutrell, A., Spreen, W., Hetherington, S., the CNAA3006 Study Team, (2001). A Randomized, Double-Blind Study of Triple Nucleoside Therapy of Abacavir, Lamivudine, and Zidovudine Versus Lamivudine and Zidovudine in Previously Treated Human Immunodeficiency Virus Type 1-Infected Children. Pediatrics 107: 4e-4 [Abstract] [Full Text]  
• Pearson, D. A., McGrath, N. M., Nozyce, M., Nichols, S. L., Raskino, C., Brouwers, P., Lifschitz, M. C., Baker, C. J., Englund, J. A., for the Pediatric AIDS Clinical Trials 152 St, (2000). Predicting HIV Disease Progression in Children Using Measures of Neuropsychological and Neurological Functioning. Pediatrics 106: 76e-76 [Abstract] [Full Text]  
• de Martino, M., Tovo, P.-A., Balducci, M., Galli, L., Gabiano, C., Rezza, G., Pezzotti, P., for the Italian Register for HIV Infection in Chil, (2000). Reduction in Mortality With Availability of Antiretroviral Therapy for Children With Perinatal HIV-1 Infection. JAMA 284: 190-197 [Abstract] [Full Text]  
• Italian Register for HIV Infection in Children Wri, , Galli, L, de Martino, M, Tovo, P-A, Gabiano, C, Zappa, M (2000). Predictive value of the HIV paediatric classification system for the long-term course of perinatally infected children. Int J Epidemiol 29: 573-578 [Abstract] [Full Text]  
• Committee on Pediatric AIDS, (2000). Education of Children With Human Immunodeficiency Virus Infection. Pediatrics 105: 1358-1360 [Abstract] [Full Text]  
• Nachman, S. A., Stanley, K., Yogev, R., Pelton, S., Wiznia, A., Lee, S., Mofenson, L., Fiscus, S., Rathore, M., Jimenez, E., Borkowsky, W., Pitt, J., Smith, M. E., Wells, B., McIntosh, K., for the Pediatric AIDS Clinical Trials Group 338 S, (2000). Nucleoside Analogs Plus Ritonavir in Stable Antiretroviral Therapy-Experienced HIV-Infected Children: A Randomized Controlled Trial. JAMA 283: 492-498 [Abstract] [Full Text]  
• Sharma, P. L., Crumpacker, C. S. (1999). Decreased Processivity of Human Immunodeficiency Virus Type 1 Reverse Transcriptase (RT) Containing Didanosine-Selected Mutation Leu74Val: a Comparative Analysis of RT Variants Leu74Val and Lamivudine-Selected Met184Val. J. Virol. 73: 8448-8456 [Abstract] [Full Text]  
• Hollis, S., Campbell, F. (1999). What is meant by intention to treat analysis? Survey of published randomised controlled trials. BMJ 319: 670-674 [Abstract] [Full Text]  
• Raskino, C., Pearson, D. A., Baker, C. J., Lifschitz, M. H., O'Donnell, K., Mintz, M., Nozyce, M., Brouwers, P., McKinney, R. E., Jimenez, E., Englund, J. A., for the Pediatric AIDS Clinical Trials Group 152 S, (1999). Neurologic, Neurocognitive, and Brain Growth Outcomes in Human Immunodeficiency Virus-Infected Children Receiving Different Nucleoside Antiretroviral Regimens. Pediatrics 104 : e32-e32 [Abstract] [Full Text]  
• Lindegren, M. L., Byers, R. H. Jr, Thomas, P., Davis, S. F., Caldwell, B., Rogers, M., Gwinn, M., Ward, J. W., Fleming, P. L. (1999). Trends in Perinatal Transmission of HIV/AIDS in the United States. JAMA 282: 531-538 [Abstract] [Full Text]  
• Kline, M. W., Van Dyke, R. B., Lindsey, J. C., Gwynne, M., Culnane, M., Diaz, C., Yogev, R., McKinney Jr, R. E., Abrams, E. J., Mofenson, L. M., the Pediatric AIDS Clinical Trials Group 327 , (1999). Combination Therapy With Stavudine (d4T) Plus Didanosine (ddI) in Children With Human Immunodeficiency Virus Infection. Pediatrics 103: 62e-62 [Abstract] [Full Text]  
• Wintergerst, U., Rolinski, B., Sölder, B., Bogner, J. R., Wolf, E., Jäger, H., Roscher, A. A., Belohradsky, B. H. (1999). Lack of Absorption of Didanosine after Rectal Administration in Human Immunodeficiency Virus-Infected Patients. Antimicrob. Agents Chemother. 43: 699-701 [Abstract] [Full Text]  
• (1998). Antiretroviral Therapy and Medical Management of Pediatric HIV Infection. Pediatrics 102: 1005-1062 [Full Text]  
• Palumbo, P. E., Raskino, C., Fiscus, S., Pahwa, S., Fowler, M. G., Spector, S. A., Englund, J. A., Baker, C. J. (1998). Predictive Value of Quantitative Plasma HIV RNA and CD4+ Lymphocyte Count in HIV-Infected Infants and Children. JAMA 279: 756-761 [Abstract] [Full Text]  
• Kline, M. W., Van Dyke, R. B., Lindsey, J. C., Gwynne, M., Culnane, M., McKinney Jr, R. E., Nichols, S., Mitchell, W. G., Yogev, R., Hutcheon, N., the AIDS Clinical Trials Group 240 Team, (1998). A Randomized Comparative Trial of Stavudine (d4T) Versus Zidovudine (ZDV, AZT) in Children With Human Immunodeficiency Virus Infection. Pediatrics 101: 214-220 [Abstract] [Full Text]  
• Committee on Pediatric AIDS, (1998). Surveillance of Pediatric HIV Infection. Pediatrics 101: 315-319 [Abstract] [Full Text]  
• Hammer, S. M., Squires, K. E., Hughes, M. D., Grimes, J. M., Demeter, L. M., Currier, J. S., Eron, J. J., Feinberg, J. E., Balfour, H. H., Deyton, L. R., Chodakewitz, J. A., Fischl, M. A., Phair, J. P., Pedneault, L., Nguyen, B.-Y., Cook, J. C., The AIDS Clinical Trials Group 320 Study Team, (1997). A Controlled Trial of Two Nucleoside Analogues plus Indinavir in Persons with Human Immunodeficiency Virus Infection and CD4 Cell Counts of 200 per Cubic Millimeter or Less. NEJM 337: 725-733 [Abstract] [Full Text]  
• (1997). Antiretroviral Therapy for Children. AIDS Clin Care 1997: 3-3 [Full Text]