PharmAdapt: a randomized prospective study to evaluate the benefit of therapeutic monitoring of protease inhibitors: 12 week results.

OBJECTIVE: A randomized study to evaluate the usefulness of protease inhibitor (PI) therapeutic drug monitoring (TDM) in antiretroviral-experienced HIV-infected patients.
METHODS: In the control arm, treatment was modified according to genotypic resistance testing. In the TDM arm, therapy was modified on the basis of genotypic resistance testing and at week 8 according to PI plasma trough levels measured at week 4. The major endpoint was the change in HIV-RNA levels at week 12.
RESULTS: A total of 183 patients, 96 in the control arm and 87 in the TDM arm, were included in the study. Low-dose ritonavir to enhance the associated PI was prescribed to 62.5% of patients in the control arm and 65.5% of patients in the TDM arm. Using our PI concentration targets, 17/81 patients (21%) in the TDM arm were considered to have suboptimal or partly optimal PI plasma levels at week 4. Physician and protocol-driven PI modifications were performed in 18/85 patients (23.5%) in the TDM arm, and in seven of 94 patients (7%) in the control arm (P < 0.01). Week 12 HIV RNA dropped 2 log10 copies/ml in the control arm and 1.7 log10 copies/ml in the TDM arm, respectively.
CONCLUSION: We found no statistically significant difference between the TDM arm and control arm in virological outcome at week 12. The utility of TDM could be dependent on the presence of low-dose ritonavir as a booster and the antiretroviral experience of the studied population. Effective non-toxic target concentrations for resistant viruses have still to be determined. Copyright 2002 Lippincott Williams &; Wilkins

RCT Entities:   Population Interventions Outcomes