title: Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation.
abstract: OBJECTIVE
  Though combination antiretroviral therapy reduces the concentration of HIV-1 RNA in both plasma and cerebrospinal fluid (CSF) below the detection limit of clinical assays, low levels of HIV-1 RNA are frequently detectable in plasma using more sensitive assays. We examined the frequency and magnitude of persistent low-level HIV-1 RNA in CSF and its relation to the central nervous system (CNS) immune activation.
  
  
  METHODS
  CSF and plasma HIV-1 RNA were measured using the single-copy assay with a detection limit of 0.3 copies/ml in 70 CSF and 68 plasma samples from 45 treated HIV-1-infected patients with less than 40 copies/ml of HIV-1 RNA in both fluids by standard clinical assays. We also measured CSF neopterin to assess intrathecal immune activation. Theoretical drug exposure was estimated using the CNS penetration-efficacy score of treatment regimens.
  
  
  RESULTS
  CSF HIV-1 RNA was detected in 12 of the 70 CSF samples (17%) taken after up to 10 years of suppressive therapy, compared to 39 of the 68 plasma samples (57%) with a median concentration of less than 0.3 copies/ml in CSF compared to 0.3 copies/ml in plasma (P < 0.0001). CSF samples with detectable HIV-1 RNA had higher CSF neopterin levels (mean 8.2 compared to 5.7 nmol/l; P = 0.0085). Patients with detectable HIV-1 RNA in CSF did not differ in pretreatment plasma HIV-1 RNA levels, nadir CD4 cell count or CNS penetration-efficacy score.
  
  
  CONCLUSIONS
  Low-level CSF HIV-1 RNA and its association with elevated CSF neopterin highlight the potential for the CNS to serve as a viral reservoir and for persistent infection to cause subclinical CNS injury.
authors.affiliation: aDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet and Swedish Institute for Communicable Disease Control, Stockholm, Sweden bDepartment of Neurology, University of California San Francisco, San Francisco, USA cDivision of Biological Chemistry, Biocentre, Innsbruck Medical University, Innsbruck, Austria dDepartment of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden eCentre for Virus Research, Westmead Millennium Institute, Westmead fThe University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Viktor
authors.initials: V
authors.lastname: Dahl
authors.forename: Julia
authors.initials: J
authors.lastname: Peterson
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.forename: Magnus
authors.initials: M
authors.lastname: Gisslen
authors.forename: Sarah
authors.initials: S
authors.lastname: Palmer
authors.forename: Richard W
authors.initials: RW
authors.lastname: Price
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000821:virology*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000134:cerebrospinal fluid*; D010949:Plasma / Q000821:virology; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid*; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral; D019798:Neopterin