ABSTRACT
Human immunodeficiency virus type 1 (HIV-1) RNA can be detected in the cerebrospinal fluid (CSF) of 75-90% of all HIV-infected patients. However, it is not yet known which factors influence the amount of HIV-1 in the CSF, either qualitatively or quantitatively. We have analysed HIV-1 RNA in CSF samples from 24 HIV-infected patients using zidovudine who underwent lumbar puncture in order to establish a diagnosis for a neurological disorder. Several factors were examined for possible correlation with the amount of HIV-1 RNA in the CSF: age, gender, the medical indication for lumbar puncture, the most recent CD4 cell count in blood, zidovudine dose, duration of treatment with zidovudine, the zidovudine concentration in plasma and CSF, and the total protein concentration in plasma and CSF. The only statistically significant factor was the total protein level in the CSF, which showed a positive relation with the amount of HIV-1 RNA in the CSF. This study indicates that increased levels of HIV-1 RNA in the CSF of neurologically symptomatic patients are the result of damage to the blood-brain barrier.
Subject(s)
AIDS Dementia Complex/etiology , Blood-Brain Barrier , HIV Infections/virology , HIV-1/isolation & purification , RNA, Viral/cerebrospinal fluid , Adult , CD4 Lymphocyte Count , Female , HIV Infections/cerebrospinal fluid , HIV-1/genetics , Humans , Male , Middle AgedABSTRACT
It has been hypothesized that didanosine has a low efficacy in the prevention and treatment of patients with the dementia complex of acquired immunodeficiency syndrome (AIDS) because "... the drug has not been detected in the cerebrospinal fluid". We investigated didanosine concentrations in cerebrospinal fluid (CSF) and plasma of four patients with AIDS who were using didanosine chronically. Didanosine levels, 4 h after the last drug administration, averaged 0.16 (+/- 0.03) mumol/l in CSF and 0.70 (+/- 0.27) mumol/l in plasma. When compared with historical data from patients using zidovudine, didanosine concentrations in CSF appeared to be approximately half (on a molar base) those of zidovudine concentrations in the CSF. Whether this difference in CSF levels is the explanation for the presumed lower efficacy of didanosine in the prevention and treatment of AIDS dementia complex remains to be proven. However, it is clear from this study, in contrast with earlier suggestions, that didanosine is able to pass the blood-CSF barrier in human immunodeficiency virus-infected individuals.
