VIRADAPT: Efficacy According to Drug Levels & Randomization Arm
Notes:
In a prospective randomized study, the impact of plasma protease inhibitor (PI) trough levels on changes in HIV RNA were assessed in patients treated with genotypic-guided therapy. Patients failing combination therapy (HIV-1 RNA > 10,000 copies/ml, and at least 6 months of therapy with nucleoside analogues and 3 months with PI) were randomly assigned into two arms: control group (C) in which the treatment was modified according to the standard of care; genotypic group (G) in which the treatment was modified according to resistance mutation profiles. In this pharmacokinetic substudy, 81 patients had 575 serial PI levels done over the 12 month study period.
Optimal conc. (OC) if ³2 samples >IC50; Suboptimal conc. (SOC) if ³2 samples <IC50
Viral load reductions at 48 weeks: Genotype Control
OC 1.33 (±0.19) 0.92 (±0.28)
SOC 0.835 (±0.41) 0.27 (±0.29)
In a multivariate analysis: OR (95% CI) p
PI level > IC50 2.48 (1.75-114) 0.013
use of genotyping 2.20 (1.23-31.79) 0.027
presence 1o PI mutations 2.67 (0.012-0.50) 0.008
baseline viral load 1.79 (0.07-1.12) 0.07
Durant J. Clevenbergh P. Garraffo R. Halfon P. Icard S. Del Giudice P. Montagne N. Schapiro JM. Dellamonica P. Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study. AIDS 2000;14(10):1333-9.