ABSTRACT: Objectives: We assessed in a prospective randomized study the relevance of plasma protease inhibitor (PI) trough level in patients failing combination therapy (HIV-1 RNA >10000 copies/ml, at least 6 month treatment with nucleoside analogues and 3 months with protease inhibitors) managed with genotypic assay.
Methods: Patients were randomized in two arms: control group (C), treatment modifed according to standard of care; and genotypic group (G), treatment modified according to resistance mutations. Analysis was on an intent-to-treat basis with the viral load as the primary endpoint. Monthly PI plasma levels were analysed in patients for 6 months. The levels of the PIs were determined by HPLC. Suboptimal concentration (SOC) was defined as at least two PI plasma levles below wild-type strain IC50. Others were considered as optimal concentration (OC). Patients were categorized in four groups: G1 (SOC/control),
Results: Eighty-five patients [mean age of 39.7±8 years, 81 males, stage CDC C (52.7%)] were included. The two groups were comparable in terms of risk factor, age, sex, previous treatment, CD4 cell counts, log10HIV-1 RNA at baseline and mean PI plasma concentrations. Linear regression analysis showed a significant relationship between PI concentration and decline of HIV RNA in plasma. 28.2% (24/85) had SOC of drug. Mean change in HIV RNA from baseline at month 6 were: -0.27±0.29 (G1), -0.92±0.28 (G2), -0.835±0.41 (G3), -1.33±0.19 (G4) log10copies/ml. PI plasma concentration was an independent predictive value of HIV RNA evolution [RR 2.48 (1.75-114); P=0.013] in a multivariate analysis.
Conclusions: Multiple parameters determine the response to antiretroviral therapy and other causes than development of drug resistance should be considered. Therapeutic drug monitoring of PI plasma concentration could be recommended to optimize antiretroviral therapy.
