Virological and pharmacological parameters predicting the response to lopinavir-ritonavir in heavily protease inhibitor-experienced patients.
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.
Marcelin
Anne-Geneviève
AG
Department of Virology, Pitié-Salpêtrière Hospital, 83 Boulevard de l'hôpital, 75013 Paris, France. anne-genevieve.marcelin@psl.ap-hop-paris.fr
Cohen-Codar
Isabelle
I
King
Martin S
MS
Colson
Philippe
P
Guillevic
Emmanuel
E
Descamps
Diane
D
Lamotte
Claire
C
Schneider
Véronique
V
Ritter
Jacques
J
Segondy
Michel
M
Peigue-Lafeuille
Hélène
H
Morand-Joubert
Laurence
L
Schmuck
Anne
A
Ruffault
Annick
A
Palmer
Pierre
P
Chaix
Marie-Laure
ML
Mackiewicz
Vincent
V
Brodard
Véronique
V
Izopet
Jacques
J
Cottalorda
Jacqueline
J
Kohli
Evelyne
E
Chauvin
Jean-Pierre
JP
Kempf
Dale J
DJ
Peytavin
Gilles
G
Calvez
Vincent
V
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*
D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D019438:Ritonavir