Open AccessVirological and Pharmacological Parameters Predicting the Response to Lopinavir-Ritonavir in Heavily Protease Inhibitor-Experienced Patients
Author(s) -
AnneGeneviève Marcelin,
Isabelle Cohen-Codar,
Martin King,
Philippe Colson,
Emmanuel Guillevic,
Diane Descamps,
C. Lamotte,
Véronique Schneider,
Jacques Ritter,
Michel Segondy,
H. Peigue-Lafeuille,
Laurence MorandJoubert,
Anne Schmuck,
Annick Ruffault,
Pierre Palmer,
MarieLaure Chaix,
Vincent Mackiewicz,
Véronique Brodard,
Jacques Izopet,
J. Cottalorda,
Évelyne Kohli,
JeanPaul Chauvin,
Dale J. Kempf,
Gilles Peytavin,
Vincent Cálvez
Publication year - 2005
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.49.5.1720-1726.2005
Subject(s) - lopinavir , ritonavir , lopinavir/ritonavir , protease inhibitor (pharmacology) , virology , protease , medicine , drug resistance , pharmacology , biology , viral load , immunology , human immunodeficiency virus (hiv) , antiretroviral therapy , microbiology and biotechnology , enzyme , biochemistry
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.