Abstract 260B - Usefulness of Protease Inhibitor Therapeutic Drug Monitoring? PharmAdapt : A Prospective Multicentric Randomized Controlled Trial: 12 Weeks Results

260B Usefulness of Protease Inhibitor Therapeutic Drug Monitoring? PharmAdapt : A Prospective Multicentric Randomized Controlled Trial: 12 Weeks Results

P. Clevenbergh*¹, J. Durant¹, R. Garraffo¹, M. Kirstetter², J. P. Daures³, P. Dellamonica¹, and Infectio-SUD Group.
Univ. Hosp.,¹Nice,²Paris, and³Nimes, France

Background:Protease inhibitors (PI) seem to be good candidates for TDM. Objective : to evaluate the usefulness of PI TDM in pretreated patients.

Design/Methods: We randomized HIV-infected patients (pts) failing therapy (HIV RNA > 2000 copies/ml, treatment with at least 6 months NRTI and/or NNRTI and/or PI) into 2 arms. In the control arm (PK-), treatment was modified according to genotypic resistance testing. In the study arm (PK+), therapy was modified according to genotypic resistance testing and PI plasma trough levels measured at week 4. The chosen cutoff for optimal PI concentration was trough level higher than the protein-adjusted IC50 for WT strains. The end-points were the changes in HIV-RNA and the proportion of pts with a HIV-RNA below level of quantification at week 12. Statistical analysis was performed on an Intent-To-Treat basis.

Results:256 pts were randomized into: PK- arm: 131 pts, PK+ arm: 125 pts. A PI containing regimen was given in 178/256 (69%) pts. Low dose ritonavir to enhance PI was prescribed in 60% pts (PK-) and 61% (PK+) at study entry. At week 4, suboptimal PI trough levels was found in: IDV : 8% / 21%, SQV 0% / 75%, NFV 23% / 0%, APV : 5%/12%, lopinavir: 0% /0%, RTV : 69%/64%, in PK- and PK+ arms, respectively. PI modification at W8 was performed in 10% (PK-, physician driven) versus 22 % (PK+, physician and protocol driven) (p = 0.02). At week 12, in PI treated patients, median drop in HIV-RNA was comparable in both arms : 2.61 log10 copies /ml (PK-) versus 2.32 log10 copies /ml (PK+) (p=.3). At W 12, HIV-RNA was below level of detection in 50% pts (PK-) versus 43% pts (PK+) (p=.38).

Conclusions:Virologic outcome was comparable in both arms. Frequent use of low dose ritonavir enhanced PI containing regimens at baseline could have diminished the benefit of PI therapeutic drug monitoring. The chosen cutoff for optimal concentration, clinician’s adherence to genotypic/pharmacologic recommendations, and patient’s compliance could have affected the results. Use of TDM to monitor drug toxicity has still to be