Article

Cerebrospinal fluid HIV infection and pleocytosis: Relation to systemic infection and antiretroviral treatment

Department of Neurology, University of California, San Francisco, USA.
BMC Infectious Diseases (Impact Factor: 2.61). 11/2005; 5(1):98. DOI: 10.1186/1471-2334-5-98
Source: PubMed

ABSTRACT

Central nervous system (CNS) exposure to HIV is a universal facet of systemic infection. Because of its proximity to and shared barriers with the brain, cerebrospinal fluid (CSF) provides a useful window into and model of human CNS HIV infection.
Prospective study of the relationships of CSF to plasma HIV RNA, and the effects of: 1) progression of systemic infection, 2) CSF white blood cell (WBC) count, 3) antiretroviral therapy (ART), and 4) neurological performance. One hundred HIV-infected subjects were cross-sectionally studied, and 28 were followed longitudinally after initiating or changing ART.
In cross-sectional analysis, HIV RNA levels were lower in CSF than plasma (median difference 1.30 log10 copies/mL). CSF HIV viral loads (VLs) correlated strongly with plasma VLs and CSF WBC counts. Higher CSF WBC counts associated with smaller differences between plasma and CSF HIV VL. CSF VL did not correlate with blood CD4 count, but CD4 counts <50 cells/microL associated with a low prevalence of CSF pleocytosis and large differences between plasma and CSF VL. CSF HIV RNA correlated neither with the severity of the AIDS dementia complex (ADC) nor abnormal quantitative neurological performance, although these measures were associated with depression of CD4 counts. In subjects starting ART, those with lower CD4 counts had slower initial viral decay in CSF than in plasma. In all subjects, including five with persistent plasma viremia and four with new-onset ADC, CSF HIV eventually approached or reached the limit of viral detection and CSF pleocytosis resolved.
CSF HIV infection is common across the spectrum of infection and is directly related to CSF pleocytosis, though whether the latter is a response to or a contributing cause of CSF infection remains uncertain. Slowing in the rate of CSF response to ART compared to plasma as CD4 counts decline indicates a changing character of CSF infection with systemic immunological progression. Longer-term responses indicate that CSF infection generally responds well to ART, even in the face of systemic virological failure due to drug resistance. We present simple models to explain the differing relationships of CSF to plasma HIV in these settings.

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Available from: Ellen E Paxinos, Jul 13, 2014
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    • "While not true for all individuals, it is often observed that measured HIV-1 RNA levels in the CSF are anywhere from 1-2 log10 lower than those measured in contemporaneous plasma [72,73]. In an attempt to determine if the differences observed in genetic diversity (APD) of the paired CSF and plasma compartments in the group was simply a refection of differences in HIV-1 RNA levels (VL) within the compartments, linear regression analysis comparing the ratio of each individuals’ plasma to CSF APD to the log of the ratio of the plasma to CSF VL was performed. "
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    • "Analysis of one or a few novel biomarkers using multiplex assays is relatively straightforward at this exploratory level because of the circumscribed number of variables examined. This type of cross-sectional design can be supplemented by longitudinal studies to define the natural history and progression or response to therapy of individual subjects (Spudich et al. 2005b). "
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