AEGiS-15IAC: The ATSAQ-1 cohort study: Pharmacokinetic interactions of atazanavir (AZV) and saquinavir (SQV) in a ritonavir (RTV) boosted protease inhibitor therapy regimen.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

The ATSAQ-1 cohort study: Pharmacokinetic interactions of atazanavir (AZV) and saquinavir (SQV) in a ritonavir (RTV) boosted protease inhibitor therapy regimen.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. WeOrB1235)

von Hentig NH, Mueller A, Haberl A, Lutz T, Knecht G, Kurowski M, Harder S, Staszewski S
University Hospital Pharmazentrum, Frankfurt/M., Germany

BACKGROUND: Recently it has been demonstrated that AZV independently from RTV may act as a pharmaco-enhancer for SQV. Therefore concomitant boosting of SQV with AZV and RTV may be an option for salvage therapy. OBJECTIVE: To investigate potential pharmacokinetic (PK) interactions of AZV, SQV and RTV in patients.

METHODS: We determined steady state plasma drug levels of AZV, SQV and RTV in 25 HIV-1 infected adult patients, taking SQV 1000mg BID and AZV 300/RTV 100mg QD. The results were compared to PK data from 55 patients treated with SQV 1000mg/RTV 100mg BID + 2 or 3 reverse transcriptase inhibitors (RTI) (LOPSAQ study) and 15 patients treated with AZV 300/RTV 100mg BID +2 or 3 RTI.

RESULTS: Non-compartmental analysis: [table: see text]Dosing interval: *24h; **12h. Dosing interval: *24h; **12h. Differences between groups - Mann Whitney U-test: [table: see text] Dosing interval: *24h; **12h. Differences between groups - Mann Whitney U-test:[table: see text]

CONCLUSIONS: In a boosted double PI regimen of AZV/SQV/RTV, AZV plasma levels were not affected by SQV, whereas SQV levels were significantly increased by AZV/RTV. This effect turned out to be significantly greater than with RTV alone. Atazanavir also acts as a booster for RTV. Exposure to RTV was significantly higher with the AZV-containing regimen compared to SQV/RTV. Lower Cmin of RTV in AZV/RTV treated patients are due to the QD dosing of RTV at 100mg. In a boosted double PI regimen of AZV/SQV/RTV, AZV and SQV do not require dose adjustment. However high RTV plasma levels could be associated with increased toxicity.

Keywords: AEGIS, Saquinavir, Ritonavir, Protease Inhibitors, Drug Interactions, HIV Protease Inhibitors, Reverse Transcriptase Inhibitors, HIV-1, Pyridines, Drug Therapy, Combination, Cohort Studies, Area Under Curve, Antiretroviral Therapy, Highly Active, Biological Availability, atazanavir, Adult, Humans, pharmacokinetics, therapy, drug therapy

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WeOrB1235