title: Virological and pharmacological parameters predicting the response to lopinavir-ritonavir in heavily protease inhibitor-experienced patients.
abstract: The genotypic inhibitory quotient (GIQ) has been proposed as a way to integrate drug exposure and genotypic resistance to protease inhibitors and can be useful to enhance the predictivity of virologic response for boosted protease inhibitors. The aim of this study was to evaluate the predictivity of the GIQ in 116 protease inhibitor-experienced patients treated with lopinavir-ritonavir. The overall decrease in human immunodeficiency virus type 1 (HIV-1) RNA from baseline to month 6 was a median of -1.50 log(10) copies/ml and 40% of patients had plasma HIV-1 RNA below 400 copies/ml at month 6. The overall median lopinavir study-state C(min) concentration was 5,856 ng/ml. Using univariate linear regression analyses, both lopinavir GIQ and the number of baseline lopinavir mutations were highly associated with virologic response through 6 months. In the multivariate analysis, only lopinavir GIQ, baseline HIV RNA, and the number of prior protease inhibitors were significantly associated with response. When the analysis was limited to patients with more highly mutant viruses (three or more lopinavir mutations), only lopinavir GIQ remained significantly associated with virologic response. This study suggests that GIQ could be a better predictor of the virologic response than virological (genotype) or pharmacological (minimal plasma concentration) approaches used separately, especially among patients with at least three protease inhibitor resistance mutations. Therapeutic drug monitoring for patients treated by lopinavir-ritonavir would likely be most useful in patients with substantially resistant viruses.
authors.affiliation: Department of Virology, Pitié-Salpêtrière Hospital, 83 Boulevard de l'hôpital, 75013 Paris, France. anne-genevieve.marcelin@psl.ap-hop-paris.fr
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cohen-Codar
authors.forename: Martin S
authors.initials: MS
authors.lastname: King
authors.forename: Philippe
authors.initials: P
authors.lastname: Colson
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Guillevic
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
authors.forename: Claire
authors.initials: C
authors.lastname: Lamotte
authors.forename: Véronique
authors.initials: V
authors.lastname: Schneider
authors.forename: Jacques
authors.initials: J
authors.lastname: Ritter
authors.forename: Michel
authors.initials: M
authors.lastname: Segondy
authors.forename: Hélène
authors.initials: H
authors.lastname: Peigue-Lafeuille
authors.forename: Laurence
authors.initials: L
authors.lastname: Morand-Joubert
authors.forename: Anne
authors.initials: A
authors.lastname: Schmuck
authors.forename: Annick
authors.initials: A
authors.lastname: Ruffault
authors.forename: Pierre
authors.initials: P
authors.lastname: Palmer
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
authors.forename: Vincent
authors.initials: V
authors.lastname: Mackiewicz
authors.forename: Véronique
authors.initials: V
authors.lastname: Brodard
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cottalorda
authors.forename: Evelyne
authors.initials: E
authors.lastname: Kohli
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Chauvin
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Kempf
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
mesh_terms: D000328:Adult; D000368:Aged; D004338:Drug Combinations; D016903:Drug Monitoring; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D016014:Linear Models; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011237:Predictive Value of Tests; D011744:Pyrimidinones / Q000627:therapeutic use*; D012367:RNA, Viral / Q000235:genetics; D019438:Ritonavir / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D019438:Ritonavir