10th Anniversary Conference Of The British HIV Association [BHIVA]


15 – 17 April 2004, City Hall, Cardiff, UK

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[TITLE:] PHARMACOKINETICS (PKS) OF SAQUINAVIR HARD GEL (SQV-HG)/RITONAVIR (RTV) WITH ATAZANAVIR (ATV) OR FOSAMPRENAVIR (FPV) IN HIV+ PATIENTS (PTS)

[AUTHOR(S):] M Boffito1, DJ Back2, M Kurowski4, L Dickinson2, G Kruse4, A Hill3, G Moyle1, M Nelson1, C Higgs1, C Fletcher1, B Gazzard1, A Pozniak1
1Chelsea and Westminster Hospital, London, 2University of Liverpool, Liverpool, 3Roche, Welwyn, UK; 4Therapia GmbH, Berlin, Germany

BHIVA Conf 2004 Apr 15-17;10:O1

BACKGROUND: Double-boosted protease inhibitor (PI) regimens have shown promising results in HIV+ patients in salvage or when reverse transcriptase inhibitors are no longer a therapeutic option. When combining different cytochrome P450 substrates, the potential for undesirable drug interactions is enhanced.

METHODS: The PKs of SQV-hg/RTV 1000/100 and 200 mg plus FPV 700mg twice a day (n=18) and SQV-hg/RTV/ATV 1600/100/300 mg once a day (n=18) was investigated in HIV+ pts. On PK days, blood was drawn predose and 0.5,1, 2, 3, 4, 6, 8, 12 and 24 hours postdose. Safety analysis was performed at screening, PK days and follow-up. Geometric mean ratios (GMRs) and 95% confidence intervals (CI) were used to compare SQV-PK parameters ± FPV or ATV. SQV, RTV, FPV and ATV concentrations were measured by high-performance liquid chromatography (HPLC)-mass spectrometry(MS)/MS.

RESULTS: No changes in safety parameters were observed. ATV led to a reversible increase in total and indirect bilirubin after 10 days of therapy. After the addition of FPV, SQV area under the curve (AUC)0-12 (GMR, 95% CI: 0.85, 0.74–1.15), plasma drug concentration (C)trough (0.76, 0.64–1.17) and Cmax (0.91, 0.79–1.18) were slightly decreased. With a further 100 mg RTV, SQV AUC0-12 (1.09, 0.87–1.65), Ctrough (1.02, 0.81–1.74) and Cmax (1.19,0.97–1.67) slightly increased. A statistically significant increase in SQV Ctrough (2.12,1.72–3.50), Cmax (1.42, 1.24–1.94) and AUC0-24 (1.60, 1.35–2.43) was observed after the addition of ATV to the once-daily SQV/RTV-containing regimen.

CONCLUSION: SQV use in double-boosted PI-containing regimens is very promising from a safety and PK prospective.

PRESENTING AUTHOR: M Boffito

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Copyright © 2004 - British HIV Association (BHIVA) Reproduction of this abstract (other than one copy for personal reference) must be cleared through the BHIVA Organising Secretariat 1 Mountview Court, 310 Friern Barnet Lane, London N20 0LD