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Vidarabine versus Acyclovir Therapy in Herpes Simplex Encephalitis

List of authors.
  • Richard J. Whitley, M.D.,
  • Charles A. Alford, M.D.,
  • Martin S. Hirsch, M.D.,
  • Robert T. Schooley, M.D.,
  • James P. Luby, M.D.,
  • Fred Y. Aoki, M.D.,
  • Daniel Hanley, M.D.,
  • Andre J. Nahmias, M.D.,
  • Seng-Jaw Soong, P.D.,
  • and The NIAID Collaborative Antiviral Study Group*

Abstract

We randomly assigned 208 patients who underwent brain biopsy for presumptive herpes simplex encephalitis to receive either vidarabine (15 mg per kilogram of body weight per day) or acyclovir (30 mg per kilogram per day) for 10 days. Sixty-nine patients (33 percent) had biopsy-proved disease; 37 received vidarabine, and 32 acyclovir. The mortality in the vidarabine recipients was 54 percent, as compared with 28 percent in the acyclovir recipients (P = 0.008). Six-month mortality varied according to the Glasgow coma score at the onset of therapy. For scores of >10, 7 to 10, and ≤6, mortality was 42, 46, and 67 percent in the patients treated with vidarabine, as compared with 0, 25, and 25 percent in those treated with acyclovir. A six-month morbidity assessment using an adapted scoring system revealed that 5 of 37 patients receiving vidarabine (14 percent) as compared with 12 of 32 receiving acyclovir (38 percent) were functioning normally (P = 0.021). Eight vidarabine-treated patients (22 percent) and three acyclovir-treated patients (9 percent) had moderate debility. Patients under 30 years of age and with a Glasgow coma score above 10 had the best outcome with acyclovir treatment. We conclude that acyclovir is currently the treatment of choice for biopsy-proved herpes simplex encephalitis. (N Engl J Med 1986; 314:144–9.)

Funding and Disclosures

Address reprint requests to Dr. Whitley at the Department of Pediatrics, Suite 653, Children's Hospital Tower, 1600 Seventh Ave. S., University of Alabama at Birmingham, Birmingham, AL 35294.

Initiated under and supported by a contract (NOl-AI-12667) with the Development and Applications Branch of the National Institute of Allergy and Infectious Diseases, and by grants from the National Cancer Institute (CA-13148), the General Clinical Research Centers Programs (RR-032) of the National Institutes of Health, and the state of Alabama.

Author Affiliations

From the Departments of Pediatrics, Microbiology, and Biostatistics, University of Alabama at Birmingham; the Department of Medicine, Massachusetts General Hospital, Boston; the Department of Medicine, University of Texas Health Science Center at Dallas-Southwestern; the Department of Medicine, University of Manitoba, Winnipeg, Manitoba; the Department of Neurology, Johns Hopkins University, Baltimore; and the Department of Pediatrics, Emory University, Atlanta.

*The members of the National Institute of Allergy and Infectious Diseases (NIAID) Collaborative Antiviral Study Group were M. Myers (project officer), NIAID, National Institutes of Health; R. Whitley, C. Alford, S. Soong, G. Caddell, C.G. Cobbs, J. Gnann, R. Morawetz, J.W. Benton, O. Snead, Central Unit, University of Alabama at Birmingham; M.S. Hirsch, R.T. Schooley, Massachusetts General Hospital, Boston; R. Dolin, R. Betts, R. Reichman, University of Rochester; L. Corey, University of Washington; F. Aoki, G.W. Hammond, University of Manitoba, Winnipeg; M. Levin, R. Andersen, University of Colorado; A. Nahmias, H. Keyserling, S. Schwartzmann, Emory University, Atlanta; J. Wolinsky, University of Texas-Houston; D. Hanley, The Johns Hopkins University; J. Connor, S. Spector, M. Oxman, D. Richman, University of California, San Diego; F. Hayden, J. Greenlee, University of Virginia; S. Greenberg, L. Taber, Baylor University, Houston; J. Luby, University of Texas Health Science Center at Dallas-Southwestern Medical School; M. Myers, C. Linnemann, University of Cincinnati; D. Powell, Ohio State University, Columbus; D. Durak, Duke University; R. Pollard, University of Texas, Galveston; J. Joncas, St. Justine's Hospital, Montreal; G. Albert, Hôpital du Sacre-Coeur, Montreal; A. Arvin, A. Yeager (deceased), Stanford University; P. Wright, C Edwards, Vanderbilt University; T.J. Marrie, Dalhousie University, Halifax; H. Balfour, University of Minnesota; M. Marks, V. San Joaquin, University of Oklahoma; L. Frenkel, New Jersey College of Medicine and Dentistry; M. Kleiman, K. Fife, University of Indiana; K. Liu, D. Hinthorn, University of Kansas; S. Starr, S. Plotkin, University of Pennsylvania; G. Pazin, M. Ho, University of Pittsburgh; C. Sumaya, University of Texas, San Antonio; R. Baringer, University of Utah; Y. Bryson, University of California, Los Angeles; M. Cohen, S. Lemon, University of North Carolina at Chapel Hill; A. Chow, University of British Columbia, Vancouver; R. Haynes, Wright State University, Dayton, Ohio; M. Weil, Harbor–UCLA Medical Center, Torrance; A.W. Karchmer, S. Hammer, New England Deaconess Hospital, Boston; J. Tilles, University of California, Irvine; R. Buchanan, E. Marcus, S. Thornton, E. Thibodeau, Parke-Davis Company, Ann Arbor, Mich.; D. Barry, D. King, R. Keeney, R. Clemons, Burroughs Wellcome Company, Research Triangle Park, N.C.

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