title: Lopinavir/ritonavir single agent therapy as a universal combination antiretroviral therapy stopping strategy: results from the STOP 1 and STOP 2 studies.
abstract: OBJECTIVE
  We designed two different studies to evaluate two different combination antiretroviral therapy (cART) stopping strategies namely a 'staggered stop' approach (STOP 1 study) and a 'protected stop' approach (STOP 2 study) to find the best 'universal stop' strategy.
  
  
  METHODS
  Patients who stopped cART for any reason were recruited. In STOP 1, 10 patients on efavirenz continued dual nucleos(t)ide reverse transcriptase inhibitors (NRTIs) for 1 week after discontinuing efavirenz. Efavirenz concentrations were measured weekly for up to 3 weeks. In STOP 2, 20 patients stopped their cART and replaced it with two tablets of lopinavir/ritonavir (Kaletra) (100/50 mg) twice daily for 4 weeks. Lopinavir, efavirenz, nevirapine and tenofovir concentrations were measured weekly for up to 4 weeks. Virological and resistance testing were performed.
  
  
  RESULTS
  In STOP 1 five patients still had efavirenz present (median t(1/2)=148.4 h) 3 weeks after stopping. In STOP 2, 15/20 patients had a viral load (VL) of <40 copies/mL and 3/20 patients had a reduction in VL by 4 weeks. Six patients opted not to stop lopinavir/ritonavir and still had <40 copies/mL at week 8. Week 1-4 median trough lopinavir concentrations were well above the EC(95). Six patients still had detectable concentrations of original cART persisting for >1 week after stopping. No patients developed new resistance mutations.
  
  
  CONCLUSIONS
  Plasma efavirenz concentrations can persist up to 3 weeks after patients stop efavirenz-containing regimens. This suggests a strategy of stopping efavirenz only 1 week before NRTIs may not be long enough for some individuals. The use of lopinavir/ritonavir monotherapy for a 4 week period may be an alternative pharmacologically and virologically effective universal stopping strategy which warrants further investigation.
authors.affiliation: Department of Sexual Health and HIV Medicine, Directorate of Infection, Birmingham Heartlands Hospital, Birmingham, UK. steve.taylor@heartofengland.nhs.uk
authors.forename: Stephen
authors.initials: S
authors.lastname: Taylor
authors.forename: Ashini
authors.initials: A
authors.lastname: Jayasuriya
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.forename: Sris
authors.initials: S
authors.lastname: Allan
authors.forename: Ed
authors.initials: E
authors.lastname: Wilkins
authors.forename: Gerry
authors.initials: G
authors.lastname: Gilleran
authors.forename: Lisa
authors.initials: L
authors.lastname: Heald
authors.forename: Sarah
authors.initials: S
authors.lastname: Fidler
authors.forename: Andrew
authors.initials: A
authors.lastname: Owen
authors.forename: David
authors.initials: D
authors.lastname: Back
authors.forename: Erasmus
authors.initials: E
authors.lastname: Smit
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D005260:Female; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry / Q000821:virology; D019438:Ritonavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D061466:Lopinavir; D019438:Ritonavir