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The genotypic inhibitory quotient: a predictive factor of atazanavir response in HIV-1-infected treatment-experienced patients.

Solas C, Colson P, Ravaux I, Poizot-Martin I, Moreau J, Lacarelle B, Tamalet C

Laboratoire de Pharmacocinétique, Hôpital Universitaire de La Timone, Marseille, France. caroline.solas@ap-hm.fr

OBJECTIVE: To evaluate the predictive value of the genotypic inhibitory quotient (GIQ) on the atazanavir response in treatment-experienced HIV-1-infected patients. PATIENTS AND METHODS: Thirty-six patients receiving an atazanavir-containing regimen were enrolled in the study. Atazanavir plasma concentrations were measured at month (M) 1, and genotype was performed at baseline. Virologic response was defined as a viral load <400 copies/mL or a decrease > or =1 log10. RESULTS: The median numbers (range) of previous regimens, baseline protease inhibitors, and atazanavir resistance mutations were 8 (0 to 20), 3 (0 to 15), and 1 (0 to 10), respectively. The atazanavir-GIQ was associated with virologic response at M6, with a median value (range) of 365 (50 to 1172) in responder patients compared with 126 (23 to 1126) in nonresponders (P = 0.05). The cutoff value estimated for the atazanavir-GIQ was 183 (receiver operating characteristic curve test: 60% specificity, 74% sensitivity). Virologic response was achieved in 74% of patients with an atazanavir-GIQ >183 compared with only 26% of patients with an atazanavir-GIQ <183 (P = 0.02). Neither the number of mutations nor the atazanavir trough concentration was predictive of the virologic response. CONCLUSION: In pretreated patients, the atazanavir-GIQ might be useful to predict early virologic response and allow the determination of the target atazanavir trough concentration required to achieve virologic response and overcome drug resistance emergence in a given patient.

Published 9 June 2008 in J Acquir Immune Defic Syndr, 48(2): 177-80.
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