Pharmacokinetics, protein-binding-adjusted inhibitory quotients for atazanavir/ritonavir 300/100 mg in treatment-naïve HIV-infected patients.
OBJECTIVE
Studies have shown the importance of having a high protein-binding-adjusted inhibitory quotient (IQ) for protease inhibitors (PIs) boosted with ritonavir. The objective of this study was to explore the virological response when combination atazanavir/ritonavir was administered to treatment-naı¨ve patients.


METHODS
Protein-binding-adjusted IQs were calculated in 100 treatment-naı¨ve patients initiating therapy with atazanavir 300 mg/ritonavir 100 mg plus two nucleoside reverse transcriptase inhibitors.


RESULTS
The median atazanavir trough level was 635 ng/mL [interquartile range (IQR) 342-1000] and the median atazanavir protein-binding-adjusted IQ was 45 (IQR 24-71). Eighty-four per cent of patients had a successful virological response, and those who failed did not develop resistance. The IQ for boosted atazanavir is high, resulting in rare treatment failure without resistance mutations.


CONCLUSIONS
This study showed that the protein-binding-adjusted IQ of atazanavir is close to those measured for lopinavir and darunavir used once daily in first-line treatment. Finally the selection of resistance in the case of virological failure (plasma viral load 4400 HIV-1 RNA copies/mL) to atazanavir/ritonavir used in first-line therapy seems uncommon, as it is for all boosted PIs.
Lambert-Niclot
S
S
INSERM U943, AP-HP, Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France. sidonie.lambert@psl.aphp.fr
Machouf
N
N
Peytavin
G
G
Soulie
C
C
Wirden
M
M
Simon
A
A
Murphy
R L
RL
Katlama
C
C
Thomas
R
R
Calvez
V
V
Marcelin
A G
AG
D000328:Adult; D000368:Aged; D000069446:Atazanavir Sulfate; D001798:Blood Proteins / Q000378:metabolism; D024921:Drug Resistance, Multiple, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011485:Protein Binding; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
D001798:Blood Proteins; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019438:Ritonavir