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Effects of chronic zidovudine administration on CNS function and virus burden after perinatal SIV infection in rhesus
D M Rausch1, M Heyes, L E Eiden
1Section on Molecular Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, MD.
Insights
Long-term zidovudine (AZT) treatment in infant macaques delayed motor impairment and doubled lifespan by reducing virus burden. This study examined AZT
Area of Science:
- Virology
- Neuroscience
- Pediatric Infectious Diseases
Background:
- Zidovudine (AZT) showed promise for cognitive function in HIV-infected children.
- Long-term effects of AZT on perinatally infected children, including antiviral efficacy and neurodevelopment, remain under-examined.
Purpose of the Study:
- To systematically evaluate the long-term effects of zidovudine (AZT) treatment.
- To assess antiviral efficacy and impacts on cognitive and motor function in a primate model of infantile HIV infection.
Main Methods:
- Rhesus macaque infants were infected at birth with SIVSMM/B670, a model for infantile HIV.
- Infants received continuous or intermittent zidovudine (AZT) administration during the first six months post-infection.
Main Results:
- Zidovudine (AZT) administration approximately doubled lifespan.
- Treatment delayed the onset of motor impairment.
- Lowered virus burden and quinolinic acid levels in cerebrospinal fluid (CSF) were observed.
Conclusions:
- Continuous or intermittent zidovudine (AZT) administration offers significant benefits in a primate model of infantile HIV.
- AZT treatment improves survival, delays motor deficits, and reduces viral load and neuroinflammation markers.
Abstract:
Continuous intravenous administration of zidovudine (AZT) has been reported to improve cognitive function in HIV-infected pediatric patients (Pizzo et al., 1988). The effects of long-term zidovudine treatment in the perinatally infected pediatric population, including antiviral efficacy and effects on cognitive and motor function has not been systematically examined. These questions were addressed in rhesus macaque infants infected at birth with SIVSMM/B670, a primate model for infantile HIV infection and disease (Eiden et al., 1993a). Continuous or intermittent administration of AZT during the first 6 months following infection resulted in about a doubling of lifespan, a delay in the occurrence of motor impairment, and lower virus burden and quinolinic acid levels in cerebrospinal fluid (CSF) following administration of the antiviral drug.