The genotypic inhibitory quotient: a predictive factor of atazanavir response in HIV-1-infected treatment-experienced patients.
OBJECTIVE
To evaluate the predictive value of the genotypic inhibitory quotient (GIQ) on the atazanavir response in treatment-experienced HIV-1-infected patients.


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.


CONCLUSIONS
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.
Solas
Caroline
C
Laboratoire de Pharmacocinétique, Hôpital Universitaire de La Timone, Marseille, France. caroline.solas@ap-hm.fr
Colson
Philippe
P
Ravaux
Isabelle
I
Poizot-Martin
Isabelle
I
Moreau
Jacques
J
Lacarelle
Bruno
B
Tamalet
Catherine
C
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D000328:Adult; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D009842:Oligopeptides / Q000097:blood / Q000627:therapeutic use*; D011725:Pyridines / Q000097:blood / Q000627:therapeutic use*
D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate