Zidovudine reduces intrathecal immunoactivation in patients with early human immunodeficiency virus type 1 infection

Arch Neurol. 1994 Sep;51(9):943-50. doi: 10.1001/archneur.1994.00540210117021.


Objective: To evaluate the effect of zidovudine on human immunodeficiency virus type 1 (HIV-1)-associated central nervous system infection in Centers for Disease Control and Prevention stage II or III disease.

Design: In an open-ended trial, patients received 500 mg of zidovudine twice a day for 12 months. Lumbar punctures, neurological, neuropsychological, and neuroradiological examinations were repeatedly performed during the trial period and were compared with pretrial values. In 11 patients post-trial neurological follow-up of 10 to 20 months was performed.

Patients: Initially, 14 volunteers with stage II or III disease and intrathecal synthesis of HIV-1-specific antibodies were enrolled. Additionally, patients had slight neuropsychological disturbance or brain atrophy unrelated to other agents than HIV-1. Two patients dropped out because of poor compliance.

Main outcome measures: Intrathecal and systemic immune and virological responses, cognitive performance, and brain images were repeatedly monitored.

Results: After 6 weeks of zidovudine therapy, initial low-grade pleocytosis and elevated levels of beta 2-microglobulin, both in cerebrospinal fluid and in serum samples, declined. Intrathecal HIV-1 antibody synthesis could no longer be detected in half of the patients after 12 months of zidovudine therapy. Patients with defective cognition transiently improved cognitive speed and flexibility after 6 months of therapy. Slight atrophic brain changes, however, remained unchanged.

Conclusions: Zidovudine reduces intrathecal immuno-activation and transiently improves cognitive functioning in HIV-1-infected subjects who show evidence of central nervous system involvement by HIV-1 but are otherwise asymptomatic.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-CD8 Ratio
  • Central Nervous System Diseases / drug therapy*
  • Central Nervous System Diseases / etiology
  • Central Nervous System Diseases / immunology
  • Cognition Disorders / etiology
  • HIV Antibodies / analysis
  • HIV Antibodies / biosynthesis
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV-1 / immunology
  • Humans
  • Immunoglobulin G / biosynthesis
  • Male
  • Middle Aged
  • Zidovudine / therapeutic use*
  • beta 2-Microglobulin / analysis
  • beta 2-Microglobulin / cerebrospinal fluid


  • HIV Antibodies
  • Immunoglobulin G
  • beta 2-Microglobulin
  • Zidovudine