title: 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.
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.
authors.affiliation: Clinical Pharmacology Department, CHU de Nantes, Nantes, France. eric.dailly@chu-nantes.fr
authors.forename: Eric
authors.initials: E
authors.lastname: Dailly
authors.forename: Audrey
authors.initials: A
authors.lastname: Rodallec
authors.forename: Clotilde
authors.initials: C
authors.lastname: Allavena
authors.forename: Guillaume
authors.initials: G
authors.lastname: Deslandes
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Garnier
authors.forename: Eric
authors.initials: E
authors.lastname: Billaud
authors.forename: Virginie
authors.initials: V
authors.lastname: Ferré
authors.forename: Véronique
authors.initials: V
authors.lastname: Reliquet
authors.forename: Régis
authors.initials: R
authors.lastname: Bouquié
authors.forename: François
authors.initials: F
authors.lastname: Raffi
authors.forename: Pascale
authors.initials: P
authors.lastname: Jolliet
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000069454:Darunavir; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000097:blood / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D012189:Retrospective Studies; D013449:Sulfonamides / Q000097:blood / Q000627:therapeutic use*; D019562:Viral Load; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D013449:Sulfonamides; D016333:HIV Protease; D000069454:Darunavir