AEGiS-Glasgow [PL6.5] Genotypic and phenotypic inhibitory quotients as predictors of the virological response to a ritonavir/amprenavir containing regimen in HIV-1 protease inhibitor experienced patients

Seventh International Congress on Drug Therapy in HIV Infection

Glasgow, UK - 14-17 November 2004

[PL6.5] Genotypic and phenotypic inhibitory quotients as predictors of the virological response to a ritonavir/amprenavir containing regimen in HIV-1 protease inhibitor experienced patients

Int Cong Drug Therapy HIV 2004 Nov 14-18;7:Abstract No. PL6.5

A.G. Marcelin¹, C. Delaugerre¹, N. Ktorza¹, H. Ait-Mohand¹, M. Wirden¹, A. Simon¹, C. Lamotte 2 , P. Bossi¹, F. Bricaire¹, D. Costagliola¹, C. Katlama¹, G. Peytavin², V. Calvez¹
¹Virology, Pitie-Salpetriere Hospital, Paris; ²Clinical Pharmacy, Bichat-Claude Bernard Hospital, Paris, France

Virological response (VR) to protease inhibitors (PI) depends of both resistance and PK. Inhibitory quotients (C_min divided by resistance levels) integrate these two parameters. We assessed the determinants of the VR to a ritonavir (100 mg bid) + amprenavir (600 mg bid) containing regimen in PI experienced but amprenavir naïve patients.

Forty-nine patients, experiencing virological failure, were prospectively followed during 12 weeks including measure of HIV-1 viremia, APV C_min, genotype and phenotype (ViroLogic).

The VR was - 1.32 log at W12. Genotypic score (number of mutations among L10F/I/V, K20M/R, E35D, R41K, I54V, L63P, V82A/F/T/S and I84V) as well as APV W8 C_min were predictive of the VR. But the genotypic inhibitory quotient (W8 APV C_min divided by the number of mutations among the APV genotypic score) was a better predictor (P=0.001) of VR than genotype or C_min used separately. APV phenotypic test (IC₅₀ or fold change) was trendly associated to VR (P=0.14 and P=0.09, respectively). However, the phenotypic inhibitory quotient (W8 APV C_min divided by APV IC₅₀) was predictive of the VR (P=0.01). The median PIQ value adjusted for protein binding was 10.3 that is lower to that observed in the CONTEXT trial (21.7) conducted with less PI experienced patients.

APV harbored high PIQs on resistant strains that is in accordance with an efficacy when boosted by RTV in PI experienced patients. The predictive value of APV IC₅₀ or fold change used alone are enhanced taking account of APV C_min using a PIQ approach.

SESSION 6: RESISTANCE AND PHARMACOKINETICS

2004-11-14
PL6.5

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