Benefit of therapeutic drug monitoring of protease inhibitors in HIV-infected patients depends on PI used in HAART regimen – ANRS 111 trial.

As a result of high inter-patient variability, and efficacy–concentration and toxicity–concentration relationships, optimization of HIV-protease inhibitor (PI) doses based on plasma concentrations could be beneficial. During a 48-week open prospective non-randomized interventional study of 115 protease inhibitor-naïve patients initiating an indinavir/ritonavir- or lopinavir/ritonavir-, or nelfinavir-containing therapy, protease inhibitor dose was modified when plasma trough concentrations ( Ctrough) at weeks 2, 8, 16 and 24 were outside predefined optimal concentration ranges. Failure of the strategy was defined as the proportions of patients with HIV-RNA above 200 copies/mL from weeks 24 to 48 and/or experiencing grades 2, 3 or 4 PI-related adverse events during the study; proportion of patients with last Ctrough measurement outside the concentration range was determined at each visit. Virological failure and/or occurrence of adverse event were observed in 37/94 assessable patients (39%; 95% CI: 29.4–50.0). In the on-treatment analysis, failure of the strategy was noted in 16% of indinavir/r- or lopinavir/r-treated patients (8/51; 95% CI: 7.0–28.6; virological failure: 2; adverse event: 6) but in 44% of nelfinavir-treated patients (11/25; 95% CI: 24.4–65.1; virological failure: 10; adverse event: 1); Ctrough concentrations outside the range were less frequent at the last measurement than at W2 (41% vs. 66%; P < 0.05), with proportions of 35% for indinavir/r- or lopinavir/r-treated patients, but 57% for nelfinavir-treated patients. The proposed strategy of therapeutic drug monitoring may be beneficial to indinavir/r- and lopinavir/r-treated patients, but failed to move concentrations into the predefined range and to produce the expected virological success for nelfinavir-treated patients. [ABSTRACT FROM AUTHOR]