1st EACS RESISTANCE & PHARMACOLOGY WORKSHOP
October 25 - 29, 2003 Warsaw, Poland
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9TH EUROPEAN AIDS CONFERENCE (EACS) 1st EACS RESISTANCE & PHARMACOLOGY WORKSHOP October 25 - 29, 2003 Warsaw, Poland |
| 4.1 PK and Pharmacodynamics F2/5 - PHARMACOKINETICS FROM A 48-WEEK RANDOMISED TRIAL TO EVALUATE SAFETY AND EFFICACY OF INDINAVIR/RITONAVIR 800/100 MG VERSUS SAQUINAVIR/RITONAVIR 1000/100 MG: THE MAXCMIN1 TRIAL |
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| * Justesen U., Fox Z., Pedersen C., Cahn P., Gerstoft J., Clumeck N., Duran A., Peters B., Obel N., Castagna A., Dragsted U., Lundgren J.. on behalf of the MaxCmin1 trial group |
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| Coordinating office for the MaxCmin1 trial: Copenhagen HIV Programme (CHIP), Odense, Denmark |
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Background: The MaxCmin1 trial showed virological equivalence between indinavir/ritonavir (IDV/rtv) and saquinavir/ritonavir (SAQ/rtv) but more treatment-limiting toxicities in the IDV/rtv arm.
Objectives: To identify possible differences of drug concentrations within and between the two trial regimens at week 4 and 48 and to relate these to safety and efficacy outcomes.
Methods: Drug concentrations were determined centrally on cryopreserved plasma by a validated and externally controlled HPLC assay.
Results: All IDV and SAQ Cmin concentrations were above the IC95 (100 and 80 ng/mL, respectively) without change over time (paired and unpaired samples). Rtv concentrations were higher in the IDV/rtv arm at week 4 compared to the SAQ/rtv arm (p<0.0001) but not at week 48 (p=0.18). No differences were observed in IDV and SAQ concentrations at week 4 when patients were grouped according to viral suppression (<50/400 copies/mL) over 48 weeks, actual CD4 increase or time to increase of 100 cells/µL, number of adverse events (AEs) grade 3/4 or organ specific AEs (clinical or laboratory). Women had higher rtv Cmin levels at week 4 (p<0.0001) and at week 48 (p=0.0018).
| Cmin, median (IQR) | Week 4 | Week 48 | P-value |
| IDV (all) | 1303 (755-3252)(n=83) | 1164 (482-2973) (n=48) | 0.19 |
| IDV (paired samples, n=34) | 1264 (806-3290) | 1179 (685-2940) | 0.53 |
| SAQ (all) | 854 (354-1541)(n=69) | 912 (420-1383) (n=67) | 0.98 |
| SAQ (paired samples, n=46) | 685 (333-1231) | 842 (393-1270) | 0.29 |
| Rtv in IDV/rtv arm (all) | 642 (335-1176) | 475 (288-960) | 0.26 |
| Rtv in SAQ/rtv arm (all) | 397 (246-638) | 430 (260-663) | 0.50 |
| Table (concentrations in ng/mL) | |||
Conclusion: Rtv-boosting of IDV and SAQ results in high concentrations with no tendency towards levering off over 48 weeks. IDV affects the rtv Cmin level differently than SAQ resulting in higher rtv Cmin levels in the IDV/rtv arm. Efficacy and safety outcomes were not dependent on IDV and SAQ Cmin levels at week 4. Gender may influence drug concentrations.
Presenting Author: MD Ulrik Justesen, Department of Infectious Diseases, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark, Phone: +45 65503759
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