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Original Article
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Volume 338:1345-1351 May 7, 1998 Number 19
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Failure of Cytarabine in Progressive Multifocal Leukoencephalopathy Associated with Human Immunodeficiency Virus Infection
Colin D. Hall, M.B., Ch.B., Urania Dafni, Sc.D., David Simpson, M.D., David Clifford, M.D., Patricia E. Wetherill, M.D., Bruce Cohen, M.D., Justin McArthur, M.B., B.S., M.P.H., Harry Hollander, M.D., Constantin Yainnoutsos, Ph.D., Eugene Major, Ph.D., Linda Millar, B.S., Joseph Timpone, M.D., for The AIDS Clinical Trials Group 243 Team

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ABSTRACT

Background Progressive multifocal leukoencephalopathy affects about 4 percent of patients with the acquired immunodeficiency syndrome (AIDS), and survival after the diagnosis of leukoencephalopathy averages only about three months. There have been anecdotal reports of improvement but no controlled trials of therapy with antiretroviral treatment plus intravenous or intrathecal cytarabine.

Methods In this multicenter trial, 57 patients with human immunodeficiency virus (HIV) infection and biopsy-confirmed progressive multifocal leukoencephalopathy were randomly assigned to receive one of three treatments: antiretroviral therapy alone, antiretroviral therapy plus intravenous cytarabine, or antiretroviral therapy plus intrathecal cytarabine. After a lead-in period of 1 to 2 weeks, active treatment was given for 24 weeks. For most patients, antiretroviral therapy consisted of zidovudine plus either didanosine or stavudine.

Results At the time of the last analysis, 14 patients in each treatment group had died, and there were no significant differences in survival among the three groups (P = 0.85 by the log-rank test). The median survival times (11, 8, and 15 weeks) were similar to those in previous studies. Only seven patients completed the 24 weeks of treatment. Anemia and thrombocytopenia were more frequent in patients who received antiretroviral therapy in combination with intravenous cytarabine than in the other groups.

Conclusions Cytarabine administered either intravenously or intrathecally does not improve the prognosis of HIV-infected patients with progressive multifocal leukoencephalopathy who are treated with the antiretroviral agents we used, nor does high-dose antiretroviral therapy alone appear to improve survival over that reported in untreated patients.


Source Information

From the University of North Carolina at Chapel Hill School of Medicine, Chapel Hill (C.D.H.); Harvard School of Public Health, Boston (U.D., C.Y.); Mount Sinai School of Medicine, New York (D.S.); Washington University School of Medicine, St. Louis (D.C.); Yale University School of Medicine, New Haven, Conn. (P.E.W.); Northwestern University School of Medicine, Chicago (B.C.); the Departments of Neurology and Epidemiology, Johns Hopkins School of Medicine, Baltimore (J.M.); the University of California at San Francisco School of Medicine, San Francisco (H.H.); the National Institute of Neurological Disorders and Stroke, Bethesda, Md. (E.M.); Frontier Science and Technology Research Foundation, Amherst, N.Y. (L.M.); and Washington, D.C., General Hospital, Washington, D.C. (J.T.).

Address reprint requests to Dr. Hall at the Department of Neurology, CB7025, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7025.

Full Text of this Article


Related Letters:

Progressive Multifocal Leukoencephalopathy, HIV, and Highly Active Antiretroviral Therapy
Cinque P., Casari S., Bertelli D., Hall C. D., Yiannoutsos C., Clifford D. B.
Extract | Full Text  
N Engl J Med 1998; 339:848-849, Sep 17, 1998. Correspondence

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