Cerebrospinal fluid HIV-1 RNA levels in asymptomatic patients with early stage chronic HIV-1 infection: support for the hypothesis of local virus replication

Objective: To assess HIV-1 RNA levels in cerebrospinal fluid (CSF) and thei r potential correlation with plasma viral load and central nervous system ( CNS) HIV-1 infection markers in stable asymptomatic patients with a CD4 T c ell count > 500 x 10(6) cells/l. Patients and methods: Consecutive patients screened for two trials were eli gible for lumbar puncture assessment. At day 0, simultaneous samples of CSF and plasma were obtained and levels of total proteins, albumin, IgG, antib odies against HIV-1 p24 antigen, HIV-1 RNA (using the polymerase chain tech nique) and white cells were measured. Results: The integrity of the blood-brain barrier was preserved (albumin in dex greater than or equal to 7) in 59 out of 70 patients (84%). Intrathecal production of antibodies against HIV-1 p24 antigen was demonstrated in 55 out of 70 individuals (78%). Viral load in CSF was significantly lower than plasma values (3.13 +/- 0.95 versus 4.53 +/- 0.53, P = 0.0001). HIV-1 RNA was not detected in CSF in only three of the 70 patients (4%). Overall, the re was a significant correlation between plasma and CSF HIV-1 RNA levels (r = 0.43, P = 0.0001); however, in 29 patients (41%) there were significant differences (> 1.5 log(10) copies/ml) between the viral loads in plasma and CSF. In the multivariate analysis, a high level of protein and white cells in CSF, but not the HIV-1 RNA plasma level, were factors independently ass ociated with a higher level of HIV-1 RNA in CSF (P = 0.0001). Conclusions: HIV-1 RNA can be detected almost always in CSF of asymptomatic patients in early stages of HIV-1 infection including those with a preserv ed integrity of the blood-brain barrier. The important discrepancies betwee n plasma and CSF viral load, and the independent association between CSF ab normalities and CSF viral load, support the hypothesis of local production of HIV-1. (C) 1999 Lippincott Williams & Wilkins.