Zidovudine treatment prolongs survival and decreases virus load in the central nervous system of rhesus macaques infected perinatally with simian immunodeficiency virus.
To assess the potential therapeutic effects of zidovudine, rhesus macaques were inoculated with simian immunodeficiency virus (SIV) strain SMM/B670 at birth and infused either continuously or intermittently with zidovudine for 6-7 months. Zidovudine did not prevent infection but did significantly increase survival time, which was associated with lower serum p26 viral core antigen levels, a lower virus burden in the cerebrospinal fluid (CSF), and lower CSF quinolinic acid levels than in untreated monkeys. Two of 5 infected, untreated monkeys developed motor impairment within 6 months following infection, whereas motor impairments did not occur in infected, zidovudine-treated monkeys until after the drug was discontinued. Zidovudine treatment was well tolerated by rhesus infants with minimal, transient side effects. These results demonstrate that zidovudine treatment significantly decreases virus load within the central nervous system (CNS) and delays the onset of CNS dysfunction and immune disease in rhesus monkeys perinatally infected with SIV.
Rausch
D M
DM
Section on Molecular Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Heyes
M P
MP
Murray
E A
EA
Eiden
L E
LE
D000818:Animals; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002490:Central Nervous System / Q000821:virology*; D002555:Cerebrospinal Fluid / Q000821:virology*; D003643:Death; D005260:Female; D008253:Macaca mulatta; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017378:Quinolinic Acid / Q000134:cerebrospinal fluid; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification* / Q000502:physiology; D013997:Time Factors; D014758:Viral Core Proteins / Q000097:blood; D015215:Zidovudine / Q000097:blood / Q000627:therapeutic use*
D014758:Viral Core Proteins; D015215:Zidovudine; D017378:Quinolinic Acid