title: Prevalence and Correlates of Persistent HIV-1 RNA in Cerebrospinal Fluid During Antiretroviral Therapy.
abstract: BACKGROUND
  Neurocognitive disorders remain common among human immunodeficiency virus (HIV)-positive adults, perhaps owing to persistent HIV-1 RNA in cerebrospinal fluid (CSF) during antiretroviral therapy (ART).
  
  
  METHODS
  Using a single-copy assay, we measured HIV-1 RNA levels in CSF and plasma specimens from 220 HIV-positive adults who were taking suppressive ART. Fifty-five participants were tested twice.
  
  
  RESULTS
  HIV-1 RNA was detected in 42.3% of CSF and 65.2% of plasma samples. Correlates of higher CSF HIV-1 RNA levels included higher nadir and current CD4+T-cell counts, a plasma HIV-1 RNA level of ≥ 1 copy/mL, and a lower central nervous system penetration-effectiveness score (model P < .001). Worse neurocognitive performance was associated with discordance in HIV-1 RNA detection between plasma and CSF, lower overall CSF HIV-1 RNA level, and longer ART duration, among others (model P < .001). In the longitudinal subgroup, CSF HIV-1 RNA persisted in most participants (69%) over 7 months.
  
  
  CONCLUSIONS
  Low-level HIV-1 RNA in CSF is common during suppressive ART and is associated with low-level HIV-1 RNA in blood, better immune status, and lower ART drug distribution into CSF. The association between HIV-1 RNA discordance and HIV-associated neurocognitive disorder (HAND) may reflect compartmentalization. The relationship between HAND, lower HIV-1 RNA levels in CSF, and lower CD4+T-cell counts may reflect disturbances in the immune response to HIV-1 in the CNS.
authors: Emory University School of Medicine, Atlanta, Georgia.
authors: Albert M
authors: AM
authors: Anderson
authors: Germans Trias i Pujol University Hospital, Barcelona, Spain.
authors: Jose A
authors: JA
authors: Muñoz-Moreno
authors: bioMONTR Labs, Research Triangle Park, North Carolina.
authors: Daniel R
authors: DR
authors: McClernon
authors: University of California, San Diego.
authors: Ronald J
authors: RJ
authors: Ellis
authors: University of California, San Diego.
authors: Debra
authors: D
authors: Cookson
authors: Washington University, St. Louis, Missouri.
authors: David B
authors: DB
authors: Clifford
authors: University of Washington, Seattle.
authors: Ann C
authors: AC
authors: Collier
authors: University of Texas Medical Branch, Galveston.
authors: Benjamin B
authors: BB
authors: Gelman
authors: University of Washington, Seattle.
authors: Christina M
authors: CM
authors: Marra
authors: Johns Hopkins University, Baltimore, Maryland.
authors: Justin C
authors: JC
authors: McArthur
authors: University of California, San Diego.
authors: J Allen
authors: JA
authors: McCutchan
authors: Icahn School of Medicine at Mount Sinai, New York.
authors: Susan
authors: S
authors: Morgello
authors: Johns Hopkins University, Baltimore, Maryland.
authors: Ned
authors: N
authors: Sacktor
authors: Icahn School of Medicine at Mount Sinai, New York.
authors: David M
authors: DM
authors: Simpson
authors: University of California, San Diego.
authors: Donald R
authors: DR
authors: Franklin
authors: University of California, San Diego.
authors: Robert K
authors: RK
authors: Heaton
authors: University of California, San Diego.
authors: Igor
authors: I
authors: Grant
authors: University of California, San Diego.
authors: Scott L
authors: SL
authors: Letendre
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019965:Neurocognitive Disorders / Q000209:etiology / Q000821:virology; D015995:Prevalence; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid*; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral
keywords: HIV; antiretroviral therapy; cerebrospinal fluid; cognitive disorders