Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. AIDS Clinical Trials Group 243 Team

N Engl J Med. 1998 May 7;338(19):1345-51. doi: 10.1056/NEJM199805073381903.


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, respectively) 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / mortality
  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiviral Agents / therapeutic use*
  • Cytarabine / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / mortality
  • HIV-1*
  • Humans
  • Infusions, Intravenous
  • Injections, Spinal
  • Leukoencephalopathy, Progressive Multifocal / drug therapy*
  • Leukoencephalopathy, Progressive Multifocal / etiology
  • Leukoencephalopathy, Progressive Multifocal / mortality
  • Male
  • Middle Aged
  • Survival Analysis
  • Treatment Failure


  • Anti-HIV Agents
  • Antiviral Agents
  • Cytarabine