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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
Author(s) -
Dailly Eric,
Rodallec Audrey,
Allavena Clotilde,
Deslandes Guillaume,
Garnier Elisabeth,
Billaud Eric,
Ferré Virginie,
Reliquet Véronique,
Bouquié Régis,
Raffi François,
Jolliet Pascale
Publication year - 2012
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2011.00949.x
Subject(s) - darunavir , medicine , logistic regression , virology , viral load , human immunodeficiency virus (hiv) , oncology , antiretroviral therapy
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.