title: Cerebrospinal fluid HIV-1 RNA levels in asymptomatic patients with early stage chronic HIV-1 infection: support for the hypothesis of local virus replication.
abstract: OBJECTIVE
  To assess HIV-1 RNA levels in cerebrospinal fluid (CSF) and their potential correlation with plasma viral load and central nervous system (CNS) HIV-1 infection markers in stable asymptomatic patients with a CD4 T cell count >500x10(6) cells/l.
  
  
  METHODS
  Consecutive patients screened for two trials were eligible for lumbar puncture assessment. At day 0, simultaneous samples of CSF and plasma were obtained and levels of total proteins, albumin, IgG, antibodies against HIV-1 p24 antigen, HIV-1 RNA (using the polymerase chain technique) and white cells were measured.
  
  
  RESULTS
  The integrity of the blood-brain barrier was preserved (albumin index > or =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, there 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 log10 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 associated 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 preserved integrity of the blood-brain barrier. The important discrepancies between plasma and CSF viral load, and the independent association between CSF abnormalities and CSF viral load, support the hypothesis of local production of HIV-1.
authors.affiliation: Infectious Diseases Unit, Institut d'Investigacions Biomèdiques, August Pi I Sunyer Hospital Clínic, Faculty of Medicine, University of Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: García
authors.forename: G
authors.initials: G
authors.lastname: Niebla
authors.forename: J
authors.initials: J
authors.lastname: Romeu
authors.forename: C
authors.initials: C
authors.lastname: Vidal
authors.forename: M
authors.initials: M
authors.lastname: Plana
authors.forename: M
authors.initials: M
authors.lastname: Ortega
authors.forename: L
authors.initials: L
authors.lastname: Ruiz
authors.forename: T
authors.initials: T
authors.lastname: Gallart
authors.forename: B
authors.initials: B
authors.lastname: Clotet
authors.forename: J M
authors.initials: JM
authors.lastname: Miró
authors.forename: T
authors.initials: T
authors.lastname: Pumarola
authors.forename: J M
authors.initials: JM
authors.lastname: Gatell
mesh_terms: D000328:Adult; D001812:Blood-Brain Barrier; D002494:Central Nervous System Infections / Q000097:blood / Q000134:cerebrospinal fluid* / Q000821:virology; D002908:Chronic Disease; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid* / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D012367:RNA, Viral