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


METHODS
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.


METHODS
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.


METHODS
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.
Elovaara
I
I
Department of Infectious Diseases, Aurora Hospital, Helsinki, Finland.
Poutiainen
E
E
Lähdevirta
J
J
Hokkanen
L
L
Raininko
R
R
Mattinen
S
S
Virta
A
A
Suni
J
J
Ranki
A
A
D000328:Adult; D016516:CD4-CD8 Ratio; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D003072:Cognition Disorders / Q000209:etiology; D015483:HIV Antibodies / Q000032:analysis / Q000096:biosynthesis; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D015215:Zidovudine / Q000627:therapeutic use*; D001613:beta 2-Microglobulin / Q000032:analysis / Q000134:cerebrospinal fluid
D015483:HIV Antibodies; D007074:Immunoglobulin G; D001613:beta 2-Microglobulin; D015215:Zidovudine