title: A pilot, prospective, open-label simplification study to evaluate the safety, efficacy, and pharmacokinetics of once-daily lopinavir-ritonavir monotherapy in HIV-HCV coinfected patients: the MONOCO study.
abstract: BACKGROUND
  A safe, effective, easy-to-dose antiretroviral therapy that minimizes hepatic complication risk is essential in optimizing HIV-HCV treatment. Nucleoside-sparing boosted protease inhibitor monotherapy may achieve this goal.
  
  
  METHODS
  A prospective, open-label pilot simplification study of once-daily lopinavir/ritonavir (LPV/r) monotherapy in HIV-HCV coinfected patients was conducted in patients on HAART with undetectable HIV RNA for ≥6 months. The primary outcome was maintenance of HIV RNA<50 copies/mL through week 48. HIV RNA, immune measures, metabolic markers, and pharmacokinetics were assessed.
  
  
  RESULTS
  Twenty participants received once-daily LPV/r monotherapy. Mean baseline age was 46.9 years and CD4 467 cells/L. By per protocol analysis, 71.4% (95% CI, 45.4-88.3) remained on once-daily LPV/r monotherapy with virologic suppression at week 48. Virologic breakthrough (HIV RNA>50 copies/mL on 2 consecutive measures) occurred in 7 patients (mean standard error [SE] time to breakthrough, 38.3 [4.8] weeks). Resuppression occurred with improved adherence in 2 participants and improved adherence plus addition of nucleosides in 2 others. LPV C min was <1 mg/L in 8 patients and was associated with virologic breakthrough in 2 cases but with no development of resistance. No clinically significant changes in CD4, lipids, or glucose were noted. Three participants developed transient≥5-fold liver enzyme elevations. None of 9 severe adverse events were LPV/r- or liver-related. Six discontinued participation for withdrawal of consent (n=1), poor adherence (n=3), or drug intolerance (n=2).
  
  
  CONCLUSIONS
  Once-daily LPV/r monotherapy in HIV-HCV coinfected individuals offers a safe and effective approach to the management of the HIV infection, with a predictable pharmacokinetic profile.
authors: The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada. ccooper@toh.on.ca
authors: Curtis
authors: C
authors: Cooper
authors: Charles
authors: C
authors: la Porte
authors: Harout
authors: H
authors: Tossonian
authors: John
authors: J
authors: Sampalis
authors: Nabil
authors: N
authors: Ackad
authors: Brian
authors: B
authors: Conway
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D060085:Coinfection / Q000188:drug therapy*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D019438:Ritonavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D061466:Lopinavir; D019438:Ritonavir