title: Cerebrospinal fluid and plasma lopinavir concentrations and viral response in virologically suppressed patients switching to lopinavir/ritonavir monotherapy once daily.
abstract: Lopinavir/ritonavir (LPV/r) monotherapy is used in selected virologically suppressed HIV-infected patients. Some would prefer a once-daily (OD) dose instead of the usual twice-daily dose to favour adherence. However, trough concentrations of the drug in blood and particularly in cerebrospinal fluid (CSF) may not be adequate to maintain viral suppression.
  
  
  
  Prospective, open-label pilot study to evaluate the efficacy and safety of LPV/r monotherapy OD. HIV-1-infected patients, virologically suppressed for at least 6 months were enrolled. HIV viral load (VL) was determined at baseline and at weeks 4, 8, 12, 16, 24, 36 and 48. Lumbar puncture was performed in a subgroup of patients to evaluate CSF VL and CSF LPV concentrations.
  
  
  
  A total of 21 patients were included. At week 48, 85.7% (n=18) showed viral suppression (VL<40 copies/ml). Two patients had viral failure (9.5%) and a third was withdrawn from the study because of gastrointestinal symptoms. Nine patients were enrolled in the substudy. CSF VL was <40 copies/ml in all cases. Median (range) LPV concentration was 9.78 ng/ml (1.93-78.3) in CSF and 1,970 (154-16,700) ng/ml in plasma; the CSF/plasma ratio was 0.004 (0.001-0.186).
  
  
  
  In this small pilot study, LPV/r monotherapy OD maintained plasma HIV RNA suppression at 48 weeks in most patients, with no cases of CSF viral escape. However, CSF LPV concentrations were close to the 50% inhibitory concentration threshold in several patients; hence, this intervention should be avoided in patients with advanced immune suppression and/or those individuals presenting with significant comorbidities such as hepatitis C coinfection.
authors.affiliation: HIV Unit, Infectious Disease Department, Bellvitge University Hospital, L'Hospitalet, Barcelona, Spain. jmtiraboschi@bellvitgehospital.cat.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Tiraboschi
authors.forename: Hernando
authors.initials: H
authors.lastname: Knobel
authors.forename: Arkaitz
authors.initials: A
authors.lastname: Imaz
authors.forename: Judith
authors.initials: J
authors.lastname: Villar
authors.forename: Elena
authors.initials: E
authors.lastname: Ferrer
authors.forename: Maria
authors.initials: M
authors.lastname: Saumoy
authors.forename: Alicia
authors.initials: A
authors.lastname: González
authors.forename: Nerea
authors.initials: N
authors.lastname: Rozas
authors.forename: Antonia
authors.initials: A
authors.lastname: Vila
authors.forename: Jordi
authors.initials: J
authors.lastname: Niubó
authors.forename: Jordi
authors.initials: J
authors.lastname: Curto
authors.forename: Daniel
authors.initials: D
authors.lastname: Podzamczer
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D019438:Ritonavir / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D004338:Drug Combinations; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; D019438:Ritonavir