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December 28, 2006
HIV Suppressed More in CSF Than Plasma (Reuters Health)
Antiretroviral therapy has a greater impact on HIV levels in cerebrospinal fluid (CSF) than in plasma, according to a report in the December 15th issue of The Journal of Infectious Diseases.
"This response is the opposite of that predicted on the basis of the limitations of treating infection within an isolated tissue compartment," the study's authors, led by Dr. Serena S. Spudich from the University of California, San Francisco, write.
The team investigated the relationships between HIV-1 RNA levels in CSF and plasma, measures of drug resistance in each compartment, and indices of CSF inflammation in 139 treated and untreated HIV-1-infected patients and in 48 HIV-negative controls.
CSF HIV-1 RNA levels were consistently lower than those in plasma using ultrasensitive testing, the authors report, indicating "that virological 'escape' in the CSF is unusual in the setting of systemic viral suppression."
Contrary to what was seen in plasma, the results indicate, CSF HIV-1 RNA levels were much lower in subjects with failed antiretroviral therapy than in those not receiving therapy, and this reduction was maintained throughout the range of plasma HIV-1 RNA levels.
The disproportionate impact of therapy on CSF HIV-1 RNA levels was not explained by differences in susceptibility or drug resistance of organisms in the CSF and plasma, the researchers note.
Untreated patients commonly showed CSF pleocytosis, the report indicates, whereas CSF from treated patients (successful or failed) did not differ from HIV-negative controls. Treatment also reduced markers of intrathecal inflammation.
"Although one must still bear in mind the general caveat that CSF infection is not always indicative of the more-important HIV encephalitis that underlies AIDS dementia complex, to the extent that CSF findings do reflect viral events in the brain, these observations provide some optimism regarding the treatment and prevention of AIDS dementia complex, even in the face of systemic treatment failure," the authors conclude.
The investigators add, "These results may also have implications for the prevention of AIDS dementia complex in resource-poor areas of the world, where treatment options after the development of drug resistance are more limited than those in the developed world."
"Given the continued impact of HIV-associated cognitive dysfunction across the world and the evolving nature of neurological damage, we argue that it is ever more important to study the CSF in the context of HIV infection," write Dr. Justin C. McArthur from Johns Hopkins University, Baltimore, Maryland and Dr. Scott L. Letendre from University of California, San Diego, in a related editorial.
"We need the equivalent of the excellent surrogate marker plasma viral load to apply to the diagnosis, staging, and treatment of HIV-associated dementia," the editorial concludes.
