Zidovudine reduces intrathecal immunoactivation in patients with early human immunodeficiency virus type 1 infection
I. Elovaara, E. Poutiainen, J. Lahdevirta, L. Hokkanen, R. Raininko, S. Mattinen, A. Virta, J. Suni and A. Ranki
Department of Infectious Diseases, Aurora Hospital, Helsinki, Finland.
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.