McCutchan JA, Ellis R, Hsia K, Heaton R, Wallace M, Nelson J, Wolfson T, Grant I, Spector SA; HIV Neurobehavioral Research Center, UCSD, San Diego, CA.
Two studies (Brew et al. and McClernon et al.) have found elevated plasma and CSF RNA levels in HIV+ patients with dementia, but the value of CSF RNA as a correlative marker of HIV-induced cognitive dysfunction and its relationships to plasma RNA, stage of disease, and CSF pleocytosis are unclear. Using PCR (Amplicor, Roche Molecular Systems) we assayed RNA levels in 100 matched plasma and CSF samples collected routinely in patients with a broad spectrum of immunosuppression and cognitive impairment between 1990 and 1993. CSF RNA was measurable (greater than 200 copies/ml) in 83 of 100 patients (median 500, range 0-320,000) and was almost always lower than in plasma (median 17,310, range 0-580,000). Unlike plasma RNA, CSF RNA did not increase with CDC clinical stage of disease or low CD4 counts. CSF RNA correlated with degree of pleocytosis. Plasma RNA correlated with CSF RNA (N=29, r=.65, P is less than .0001) only in patients (all clinical stage A or B) with CSF pleocytosis (greater than 4 cells/ul), but not (N=34, r=.26, P greater than .10) in patients without pleocytosis (less than 2 cells/ul) who are in clinical stage C. Plasma contamination or a "leaky" blood brain barrier did not explain these findings because neither CSF RBC counts nor albumin levels correlated with CSF RNA levels. Global cognitive ratings correlated with CSF RNA weakly (N=16, r=.24, p=.05) in patients with advanced disease (CD4 less than 100), but not (n=81, r=.005, p=.52) in those with CD4 greater than 99. We conclude that in advanced AIDS CSF RNA varies independently of plasma RNA and may correlate with cognitive impairment. CSF RNA, a potential measure of CNS viral load, may be useful for diagnosis and therapeutic monitoring in HIV-induced cognitive dysfunction.
Keywords: AEGIS, HIV Infections, CD4 Lymphocyte Count, Viral Load, Acquired Immunodeficiency Syndrome, Plasma, RNA, Viral, HIV, RNA, Anti-HIV Agents, Polymerase Chain Reaction, Blood-Brain Barrier, Case-Control Studies, Human, cerebrospinal fluid, AIDS
