Phenotypic (Antivirogram®; Janssen Diagnostics BVBA, Mechelen, Belgium) and genotypic assays were performed by Janssen Diagnostics BVBA (Mechelen, Belgium) to assess the development of resistance in VFs. VF was defined as loss of (rebounders) or never achieving (never suppressed) HIV-1 RNA < 50 copies/mL. The TLOVR non-VF-censored algorithm was used as a basis for this analysis, with the following additional rules: patients who discontinued before
week 12 were not taken into account to determine VF because these patients did not have the full opportunity to show virological response; patients who had a single detectable last viral load measurement were considered VFs regardless of the reason for discontinuation. Initially, phenotypic and genotypic determinations were only performed on plasma samples with HIV-1 RNA ≥ 1000 copies/mL at screening, baseline, and weeks 24, http://www.selleckchem.com/products/ABT-263.html 48, 96 and 192 (or withdrawal). To better assess the relationship between VF and resistance, additional Hydroxychloroquine testing was also performed on samples from VFs with HIV-1 RNA ≥ 50 copies/mL. The development of a mutation was defined as the
detection of a mutation by population sequencing at endpoint that was not present at baseline or screening. Loss of phenotypic susceptibility to an antiretroviral drug was defined as having a fold-change value above the biological/clinical cut-off of the Antivirogram® at endpoint, but not at baseline. The ITT population was used for the safety analysis. The incidence and severity of AEs and laboratory abnormalities (Division of AIDS toxicity grading table) were recorded and causality was assessed by the investigator. Safety results were compared by Fisher’s exact tests. All conducted tests were two-sided. Of the 843 patients screened, 689 were randomized and treated with DRV/r 800/100 mg once daily (n = 343) or LPV/r 800/200 mg (n = 346). Of patients in the LPV/r group, 75.1% received LPV/r twice daily, 14.5% received LPV/r once daily and 10.4% switched from LPV/r twice daily to once daily. At the time of the week 192 analysis, 86.7% of patients had switched from the LPV/r capsule to tablet formulation, 11.6%
had started and remained on capsules and 1.7% see more had started and remained on tablets. In comparison, at the time of the week 48 analysis, 83% of patients had switched from the LPV/r capsule to tablet formulation, 15% had started and remained on capsules and 2% had started and remained on tablets . Baseline characteristics, as described previously , were well balanced across treatment arms and stratification factors. At baseline, 34% of patients had HIV-1 RNA ≥ 100 000 copies/mL and 42% had CD4 cell count < 200 cells/μL. The overall discontinuation rate through week 192 was lower in the DRV/r arm than in the LPV/r arm. Of the 689 randomized patients receiving treatment, 85 (24.8%) and 114 (32.9%), respectively, discontinued by week 192 (P = 0.02; post hoc analysis).