title: Benefit of therapeutic drug monitoring of protease inhibitors in HIV-infected patients depends on PI used in HAART regimen--ANRS 111 trial.
abstract: 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 (C(trough)) 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 C(trough) 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); C(trough) 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.
authors.affiliation: Inserm CIC 007, Hôpital Bichat, Paris, France. xavier.duval@bch.aphp.fr
authors.forename: Xavier
authors.initials: X
authors.lastname: Duval
authors.forename: France
authors.initials: F
authors.lastname: Mentré
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rey
authors.forename: Solange
authors.initials: S
authors.lastname: Auleley
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Michel
authors.initials: M
authors.lastname: Biour
authors.forename: Annie
authors.initials: A
authors.lastname: Métro
authors.forename: Cecile
authors.initials: C
authors.lastname: Goujard
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Taburet
authors.forename: Cecile
authors.initials: C
authors.lastname: Lascoux
authors.forename: Xaviere
authors.initials: X
authors.lastname: Panhard
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tréluyer
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon-Céron
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000378:metabolism; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral