ABSTRACT
OBJECTIVE: To determine the durability over 96 weeks of safety and efficacy of lopinavir/ritonavir (LPV/r) and raltegravir (RAL) which was demonstrated to have non-inferior efficacy relative to a regimen of LPV/r with nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) (Control) in primary analysis at 48 weeks. DESIGN: Open label, centrally randomised trial. SETTING: Recruitment was from 37 primary and secondary care sites from Africa, Asia, Australia, Europe and Latin America. SUBJECTS: 541 HIV-1 infected adults virologically failing first-line non-NRTI + 2N(t)RTI, with no previous exposure to protease inhibitors or integrase strand transfer inhibitors were analysed, 425 completed 96 weeks follow up on randomised therapy. INTERVENTION: Randomisation was 1:1 to Control or RAL. MAIN OUTCOME MEASURES: Differences between the proportion of participants with plasma HIV-1 RNA (VL) <200 copies/mL by intention to treat were compared with a non-inferiority margin of -12%. Differences in biochemical, haematological and metabolic changes were assessed using T-tests. RESULTS: VL <200 copies/mL at 96 weeks was: RAL 80.4%, Control 76.0% (difference: 4.4 [95%CI -2.6, 11.3]) and met non-inferiority criteria. The RAL arm had a significantly higher mean change (difference Control-RAL; 95%CI) in haemoglobin (-2.9; -5.7, -1.1), total lymphocytes (-0.2; -0.3, -0.0), total cholesterol (-0.5; -0.8, -0.3), HDL cholesterol (-0.1; -0.1, -0.0) and LDL cholesterol (-0.3; -0.5, -0.2). CONCLUSION: At 96 weeks, both RAL and Control maintained efficacy greater than 75% and continued to demonstrate similar safety profiles. These results support the use of a combination LPV/r and RAL regimen as an option following failure of 1st line NNRTI + 2N(t)RTIs. TRIAL REGISTRATION: ClinicalTrials.gov NCT00931463.
