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

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/mu 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.