Volume 26, Issue 4 pp. 538-542
ORIGINAL ARTICLE

Virological response to darunavir in patients infected with HIV is linked to darunavir resistance–associated mutations corrected by the count of mutations with positive impact and is not associated with pharmacological and combined virological/pharmacological parameters

Eric Dailly

Corresponding Author

Eric Dailly

Clinical Pharmacology Department, CHU de Nantes, Nantes, France

EA 4275 Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Faculté de Médecine–Pharmacie, Université de Nantes, Nantes, France

Correspondence and reprints:
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Audrey Rodallec

Audrey Rodallec

Virology Department, CHU de Nantes, Nantes, France

EA 4271 Immunovirologie et polymorphisme génétique, Faculté de médecine-pharmacie, Université de Nantes, Nantes, France

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Clotilde Allavena

Clotilde Allavena

EA 4271 Immunovirologie et polymorphisme génétique, Faculté de médecine-pharmacie, Université de Nantes, Nantes, France

Infectious Diseases Department, CHU de Nantes, Nantes, France

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Guillaume Deslandes

Guillaume Deslandes

Clinical Pharmacology Department, CHU de Nantes, Nantes, France

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Elisabeth Garnier

Elisabeth Garnier

Virology Department, CHU de Nantes, Nantes, France

EA 4271 Immunovirologie et polymorphisme génétique, Faculté de médecine-pharmacie, Université de Nantes, Nantes, France

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Eric Billaud

Eric Billaud

EA 4271 Immunovirologie et polymorphisme génétique, Faculté de médecine-pharmacie, Université de Nantes, Nantes, France

Infectious Diseases Department, CHU de Nantes, Nantes, France

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Virginie Ferré

Virginie Ferré

Virology Department, CHU de Nantes, Nantes, France

EA 4271 Immunovirologie et polymorphisme génétique, Faculté de médecine-pharmacie, Université de Nantes, Nantes, France

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Véronique Reliquet

Véronique Reliquet

EA 4271 Immunovirologie et polymorphisme génétique, Faculté de médecine-pharmacie, Université de Nantes, Nantes, France

Infectious Diseases Department, CHU de Nantes, Nantes, France

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Régis Bouquié

Régis Bouquié

Clinical Pharmacology Department, CHU de Nantes, Nantes, France

EA 4275 Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Faculté de Médecine–Pharmacie, Université de Nantes, Nantes, France

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François Raffi

François Raffi

EA 4271 Immunovirologie et polymorphisme génétique, Faculté de médecine-pharmacie, Université de Nantes, Nantes, France

Infectious Diseases Department, CHU de Nantes, Nantes, France

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Pascale Jolliet

Pascale Jolliet

Clinical Pharmacology Department, CHU de Nantes, Nantes, France

EA 4275 Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Faculté de Médecine–Pharmacie, Université de Nantes, Nantes, France

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First published: 05 May 2011
Citations: 3

Abstract

The relationships between virological (darunavir resistance–associated mutations), pharmacological (darunavir trough plasma concentration), combined virological/pharmacological [darunavir genotypic inhibitory quotient (GIQ)] parameters and virological response were evaluated in experienced patients infected with human immunodeficiency virus. In this retrospective study (48 patients), the relationship between these parameters and the virological response was investigated by multivariate logistic regression. Darunavir GIQ is defined as the ratio between darunavir trough plasma concentration and the count of darunavir resistance–associated mutations (V11I, V32I, L33F, I47V, I50V, I54L/M, T74P, L76V, I84V, L89V) corrected or not corrected by the count of mutations with positive impact (V82A and E35D). The pharmacological and combined virological/pharmacological parameters failed to predict virological response. The count of darunavir resistance–associated mutations corrected by the count of V82A and E35D mutations was the single parameter significantly (P =0.027) associated with virological response. This result suggests that both negative and positive impacts of mutations including V82A and E35D should be considered to predict virological response in experienced patients.

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