Use of different inhibitory quotients to predict early virological response to tipranavir in antiretroviral-experienced human immunodeficiency virus-infected patients.
Information about the relationship between pharmacological parameters and an early virological response to tipranavir (TPV) is scarce. Human immunodeficiency virus (HIV)-infected patients who had received TPV as part of a salvage regimen were analyzed retrospectively. A virological response was defined as a decline in the HIV RNA level of > or = 1 log unit or to <50 copies/ml between weeks 4 and 12 of therapy. The virtual inhibitory quotient (vIQ) was calculated as the ratio of the TPV plasma trough concentration (C(trough))/virtual change in the 50% inhibitory concentration. Three genotypic inhibitory quotients (gIQs) were calculated by using different TPV resistance mutation scores (from the International AIDS Society-USA [IAS-USA], Randomized Evaluation of Strategic Intervention in Multidrug-Resistant Patients with Tipranavir [RESIST], and Agence Nationale de Recherches sur le Sida et les Hépatites Virales [ANRS] trials). The sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and likelihood ratios for a positive result (LHR+) and a negative result (LHR-) [LHR+ = sensitivity/(1-specificity); LHR- = (1-sensitivity)/specificity] were calculated. A total of 57 HIV-infected patients were analyzed. A virological response was achieved by 77% of the patients. TPV resistance mutations, TPV C(trough), vIQs, and gIQs were all significantly associated with a virological response. The vIQ had the best PPV and NPV (97% and 78%, respectively). The values of the LHR+ were 7.8 for vIQ, 3.4 for the RESIST gIQ, 3.3 for the IAS-USA gIQ, 3.1 for the ANRS gIQ, 2.2 for TPV C(trough), and 1.3 for the IAS-USA and RESIST scores. The values of LHR- were 0 for the RESIST score, 0.07 for vIQ, 0.09 for the IAS-USA score, 0.27 for the RESIST gIQ, 0.32 for the IAS-USA gIQ, 0.37 for the ANRS gIQ, and 0.48 for TPV C(trough). HIV-infected patients who initiate a salvage regimen based on TPV may benefit from baseline drug resistance testing and TPV plasma concentration determination, as vIQ is the best predictor of a virological response.
Morello
Judit
J
Pharmacology Unit, Hospital Carlos III, Madrid, Spain.
De Mendoza
Carmen
C
Soriano
Vincent
V
Anta
Lourdes
L
González-Pardo
Gema
G
Corral
Angélica
A
Blanco
Francisco
F
Jiménez-Nácher
Inmaculada
I
González-Lahoz
Juan
J
Rodríguez-Novoa
Sonia
S
D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011753:Pyrones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012189:Retrospective Studies; D013449:Sulfonamides
D019380:Anti-HIV Agents; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; C107201:tipranavir