Randomized open-label trial of two simplified, class-sparing regimens following a first suppressive three or four-drug regimen

Objectives: Complex antiretroviral regimens can be associated with increased toxicity and poor adherence. Our aim was to compare the efficacy and safety of switching to two simplified, class-sparing antiretroviral regimens. Methods: We conducted a randomized, open-label study in 236 patients with virologic suppression who were taking a three- or four-drug protease inhibitor or non-nucleoside reverse transcriptase inhibitor regimen for ≥18 months. Patients received lopinavir/ ritonavir (LPV/r) 533mg/133mg twice daily+efavirenz (EFV) 600mg once daily or EFV+two nucleoside reverse transcriptase inhibitors (NRTI). Primary study endpoint was time to first virologic failure (VF, confirmed HIV-1 RNA >200copies/ml) or discontinuation because of study drug-related toxicity. Results: After 2.1 years of follow up, patients receiving LPV/r+EFV discontinued treatment at a greater rate than patients receiving EFV+NRTI (P<0.001). Twenty one patients developed VF (14 receiving LPV/r + EFV and seven receiving EFV+ NRTI) and 26 discontinued because of a study drug-related toxicity (20 receiving LPV/r + EFV and six receiving EFV + NRTI). Time to VF or study drug related-toxicity discontinuation was significantly shorter for LPV/r + EFV than EFV + NRTIs (P= 0.0015). A significantly higher risk of drug-related toxicity occurred with LPV/r + EFV, mainly for increased triglycerides (P-0021). A trend toward a higher VF rate occurred with LPV/r + EFV in an intent-to-treat and as-treated analyses (P= 0.088 and P= 0.063 respectively). Conclusions: Switching to EFV+NRTI resulted in better outcomes, fewer drug-related toxicity discontinuations and a trend to fewer virologic failures compared to switching to LPV/r+EFV.