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

Volume 330:657-662 March 10, 1994 Number 10 Next

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

ABSTRACT

Background Both didanosine and zalcitabine are commonly used to treat patients with human immunodeficiency virus (HIV) infection who cannot tolerate zidovudine treatment or who have had disease progression despite it. The relative efficacy and safety of these second-line therapies are not well defined.

Methods In this multicenter, open-label trial we randomly assigned 467 patients who previously received zidovudine and had 300 or fewer CD4 cells per cubic millimeter or a diagnosis of the acquired immunodeficiency syndrome (AIDS) to treatment with either didanosine (500 mg per day) or zalcitabine (2.25 mg per day).

Results After a median follow-up of 16 months, disease progression or death occurred in 157 of 230 patients assigned to didanosine and 152 of 237 patients assigned to zalcitabine, for a relative risk of 0.93 for the zalcitabine group as compared with the didanosine group (P = 0.56), which decreased to 0.84 (P = 0.15) after adjustment for the CD4 count, Karnofsky score, and presence of AIDS at base line. There were 100 deaths in the didanosine group and 88 in the zalcitabine group, for a relative risk of 0.78 (P = 0.09) and an adjusted relative risk of 0.63 (P = 0.003).

A majority of patients in each group (66 percent) had at least one adverse event during treatment (153 patients taking didanosine and 157 taking zalcitabine). Peripheral neuropathy and stomatitis occurred more often with zalcitabine and diarrhea and abdominal pain more frequently with didanosine.

Conclusions For patients with HIV infection who have not responded to treatment with zidovudine, zalcitabine is at least as efficacious as didanosine in delaying disease progression and death.

Source Information

From the San Francisco Community Consortium on AIDS, University of California, San Francisco (D.I.A., A.H.); the Division of Biostatistics, University of Minnesota, Minneapolis (A.I.G., C.L., J.D.N.); the Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. (J.A.K., L.D.); the Comprehensive AIDS Alliance of Detroit, Harper Hospital, Detroit (L.R.C.); Denver Community Programs for Clinical Research on AIDS, Denver Public Health, Denver (M.G., D.L.C.); Chicago Community Programs for Clinical Research on AIDS, Chicago (S.W.); R.O.W. Sciences, Rockville, Md. (K.M.); Pharmaceutical Product Development, Wilmington, N.C. (S.K.); the Department of Medicine, St. Joseph Hospital, Chicago (R.L.-H.); the Division of Infectious Diseases, Henry Ford Hospital, Detroit (N.M.); the Research and Education Group, Portland, Oreg. (J.H.S.); and AIDS Research Consortium of Atlanta, Atlanta (M.T.).

Address reprint requests to Dr. Deyton at the National Institute of Allergy and Infectious Diseases, National Institutes of Health, 6003 Executive Blvd., Bethesda, MD 20892.

Full Text of this Article

This article has been cited by other articles:

• Korn, E. L, Hunsberger, S., Freidlin, B., Smith, M. A, Abrams, J. S (2008). Comments on `Maintaining confidentiality of interim data to enhance trial integrity and credibility' by TR Fleming et al. Clin Trials 5: 364-365  
• Fleming, T. R, Sharples, K., McCall, J., Moore, A., Rodgers, A., Stewart, R. (2008). Response to the letter from Korn et al. Clin Trials 5: 365-366  
• Fleming, T. R, Sharples, K., McCall, J., Moore, A., Rodgers, A., Stewart, R. (2008). Maintaining confidentiality of interim data to enhance trial integrity and credibility. Clin Trials 5: 157-167 [Abstract]  
• Roedling, S, Pearl, D, Manji, H, Hanna, M G, Holton, J L, Miller, R F (2004). Unusual muscle disease in HIV infected patients. Sex. Transm. Infect. 80: 315-317 [Abstract] [Full Text]  
• Resino, S, Bellon, J M, Sanchez-Ramon, S, Gurbindo, D, Ruiz-Contreras, J, Leon, J A, Ramos, J T, Munoz-Fernandez, M A (2002). Impact of antiretroviral protocols on dynamics of AIDS progression markers. Arch. Dis. Child. 86: 119-124 [Abstract] [Full Text]  
• Schwarcz, S. K., Hsu, L. C., Vittinghoff, E., Katz, M. H. (2000). Impact of Protease Inhibitors and Other Antiretroviral Treatments on Acquired Immunodeficiency Syndrome Survival in San Francisco, California, 1987-1996. Am J Epidemiol 152: 178-185 [Abstract] [Full Text]  
• Grinspoon, S., Corcoran, C., Rosenthal, D., Stanley, T., Parlman, K., Costello, M., Treat, M., Davis, S., Burrows, B., Basgoz, N., Klibanski, A. (1999). Quantitative Assessment of Cross-Sectional Muscle Area, Functional Status, and Muscle Strength in Men with the Acquired Immunodeficiency Syndrome Wasting Syndrome. J. Clin. Endocrinol. Metab. 84: 201-206 [Abstract] [Full Text]  
• Collier, A. C., Coombs, R. W., Schoenfeld, D. A., Bassett, R. L., Timpone, J., Baruch, A., Jones, M., Facey, K., Whitacre, C., McAuliffe, V. J., Friedman, H. M., Merigan, T. C., Reichman, R. C., Hooper, C., Corey, L., The AIDS Clinical Trials Group, (1996). Treatment of Human Immunodeficiency Virus Infection with Saquinavir, Zidovudine, and Zalcitabine. NEJM 334: 1011-1018 [Abstract] [Full Text]  
• (1995). Antiretroviral Drug Resistance: Clinical Significance and Implications for HIV Pathogenesis. AIDS Clin Care 1995: 1-1 [Full Text]  
• Bozzette, S. A., Kanouse, D. E., Berry, S., Duan, N., R, , Gocke, D. J., Marlowe, S. I., Pottage, J. C. Jr, Follansbee, S. E., Remick, S., Klimas, N., Jensen, P., Henry, D. H., Olson, R., Turner, P. A., Lalezari, J. P., Phair, J., Pollard, R., Pierce, P. F., Saravolatz, L. D., Cohen, S., Cate, T., Pegram, P. S., Spotkov, J., Carey, J. T., Perez, G., Pettinelli, C., DownesLeGuin, T., Hill, D., Edwards, C., Mazel, R., Hays, R., Stewart, A., Soo, W., Salgo, M., Anthony, M., Dixon, D., Myers, M. (1995). Health Status and Function With Zidovudine or Zalcitabine as Initial Therapy for AIDS: A Randomized Controlled Trial. JAMA 273: 295-301 [Abstract]  
• Volberding, P. A., Lagakos, S. W., Grimes, J. M., Stein, D. S., Balfour, H. H. Jr, Reichman, R. C., Bartlett, J. A., Hirsch, M. S., Phair, J. P., Mitsuyasu, R. T., Fischl, M. A., Soeiro, R., the AIDS Clinical Trials Group of the National Ins, , Pettinelli, C. B., Martinez, A. I., Liou, S.-H., Henry, K., Simpson, M., DePaolis-Jones, A., Hewitt, R. G., Blair, D. C., Packard, M. V., Fowler, C., Crumpacker, C. S., Allan, J. D., Fitch, H. F., Dybeck, K., Coleman, R., Jacobson, M., Phair, J. P., Murphy, R., Benson, C., Hardy, W. D., Chafey, S. A., Kruger, S., Reese, J., Dale, E., Harris, C., Steigbigel, N., Becker, R. L., Rexroad, V. E., Feinberg, J. E., Spector, S. A., Richman, D. D., Snyder, R., Merigan, T. C. Jr, Fessel, J., Katzenstein, D., Zachary, J. A., Mushatt, D. M., Hyslop, N. E. Jr, Collier, A. C., Corey, L., Coombs, R. W., Para, M. F., Fass, R. J., Whitacre, C., Sacks, H. S., Mildvan, D., Mendoza, H., Fife, K., Powderly, W. G., Gelb, L. D., Klebert, M., Leedom, J. M., Liggins, M., Quesada, N., Wong, B., Brinkdopke, J., Hoelle, M., Gocke, D. J., McAuliffe, V. J., Valentine, F. T., Dowling, J., Wallace, M., PaulJarrett, V., Cargill, V., McKinley, G. F., Grieco, M. H., Polsky, B., Brown, D. C., van der Horst, C., Fiscus, S., Ragan, D., Cheeseman, S. H., Fairchild, P. G., Lai, K. K., Ho, M., McMahon, D., Armstrong, J. A., Eyster, M. E., Ehmann, W. C., Irwin, D., Steigbigel, R. T., Fuhrer, J., Tenzler, R., Ponticello, L., Giordano, M. F., Murray, H. W. (1994). The Duration of Zidovudine Benefit in Persons With Asymptomatic HIV Infection: Prolonged Evaluation of Protocol 019 of the AIDS Clinical Trials Group. JAMA 272: 437-442 [Abstract]  
• Saag, M. S. (1994). What to Do When Zidovudine Fails. NEJM 330: 706-707 [Full Text]