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Session 110 Poster Abstracts
Therapeutic Drug Monitoring
Friday, 1:30 - 3:30 pm
Hall A


639    
Prospective Trial to Evaluate how Therapeutic Drug Monitoring of Protease Inhibitors Increases Virologic Success and Tolerance of HAART (COPHAR 2 - ANRS 111 trial)
F Mentré2, Xavier Duval*1, E Rey3, G Peytavin4, S Auleley2, M Legrand2, M Biour5, A Bouxin6, C Goujard7, A M Taburet7, C Katlama8, B Diquet8, C Lascoux9, J M Tréluyer3, and D Salmon-Céron10
1Hosp Bichat-Claude Bernard, Paris, France; 2INSERM EMI 0357, Hosp Bichat-Claude Bernard, Paris, France; 3Hosp St-Vincent de Paul, Paris, France; 4Hosp Bichat-Claude Bernard, Paris, France; 5Hosp St-Antoine, Paris, France; 6French Agency for AIDS Res, Paris, France; 7Hosp Bicêtre, Paris, France; 8Hosp Pitie-Salpetriere, Paris, France; 9Hosp St-Louis, Paris, France; and 10Hosp Cochin, Paris, France

Background:  Therapeutic drug monitoring of protease inhibitor (PI) has been proposed to improve efficacy and tolerance of PI-containing HAART.

Methods:  To evaluate this hypothesis, we performed an open, non-comparative multicenter prospective trial in PI-naive patients, with repeated therapeutic drug monitoring at weeks 2, 8 or 16, 24, and 48 after the initiation of HAART including either indinavir (IDV) boosted with ritonavir (RTV), lopinavir (LPV), or the new 625-mg formulation of nelfinavir (NFV) twice daily. If trough concentrations were out of the range of 150 to 550, 2500 to 7000, or 1500 to 5500 ng/mL for IDV, LPV, and NFV, respectively, PI doses were adjusted once or more if necessary during the first 24 weeks. Adjustments were made by increments of 1 pill twice daily (200, 133/33, or 250 mg for IDV, LPV, or NFV, respectively). Failure of the strategy was defined by either 2 consecutive viral loads ≥ 200 copies/mL between weeks 16 and 48, or a PI-related adverse grade 3 or 4 and a grade 2 dose-dependent like diarrhoea or renal colic. Patients without early adverse events were defined as assessable if they had at least the week 16 virologic assessment.

Results:  A total of 115 patients were included (42 IDV, 38 LPV, 35 NFV). The percentage of patients with trough concentrations in the therapeutic ranges increased throughout the trial are shown in the table. For NFV, the high rate of below-range concentrations and the lack of success of initial dose adjustment, led to the proposition of an RTV boost that was well tolerated and efficiently increased the concentrations in 6 of 10 patients thus treated. After 48 weeks of follow-up, failure of the strategy was observed in 3, 5, and 12 patients in the IDV, LPV, and NFV groups, respectively. Among the 30, 30, and 31 assessable patients, the intent-to-treat and the on-treatment success rates were 70% and 87% in the IDV group, 73% and 81% in the LPV group, and 45% and 54% in the NFV group.

 

 

Week 2

Week 8/16

Week 24

Week 48

 IDV

51% (20/39)

69% (22/32)

77% (21/27)

76% (16/21)

 LPV

38% (13/34)

58% (19/33)

59% (17/29)

72% (18/25)

 NFV

44% (15/34)

38% (11/29)

50% (13/26)

56% (9/16)

Keywords: Protease Inhibitors; Therapeutic Drug Monitoring; Clinical Trial