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Session 64 Poster Session Therapeutic Drug Monitoring Session Time: 4:30-6:30 pm Room 4E-F

453-W. Pharmacokinetics and Genotyping in Lopinavir Recipients with Prior PI Failure M. Boffito*1,2, I. Arnaudo1, S. Bonora1, A. Sinicco1, R. Raiteri1, P. Hoggard2, D. Back2, and G. Di Perri1 1Univ. of Torino, Italy and 2Univ. of Liverpool, UK Background: Trough concentrations (Ctrough) of lopinavir (LPV) coadministered with ritonavir are reported to be 50- to 100-fold higher than the protein binding adjusted EC50 for wild type HIV, but less favourable inhibitory quotients are seen when mutations in the protease genome have been selected by prior PI intake. Methods: LPV Ctrough and baseline viral genotype were determined in 35 HIV-infected subjects who started LPV-based salvage therapy following failure with other Pis. Duration of follow up under LPV ranged between 7 and 9 months. Triplicate LPV Ctrough were measured by HPLC-MS/MS and HIV resistance patterns were determined by genotype analysis (PE-Biosystems, Foster City, CA). Responders were defined as those who had HIV-RNA < 50 copies/mL at last evaluation. Continuous variables were compared by t-test, categorical variables by chi2 test. Results: Responders (n=22) had higher mean (± SD) LPV Ctrough than non-responders (n=13) (6.5 ± 1.9 microgram/mL vs 4.9 ± 1.1 mu/mL; p=0.013730). Mean (± SD) number of PI mutations were 4.2 ± 2.4 in the former and 5.4 ± 2.9 in the latter (p=0.194409). On the 3x2 contingency table, response was associated to higher LPV Ctrough independently from the number of mutations (chi2=18.3, df=4; p=0.001095) Conclusions: Higher LPV Ctrough were associated to therapeutical response in patients having 5 or more mutations. One failure only occurred among patients with LPV Ctrough > 6 microgram/mL, suggesting that viral resistance might be overcome by increasing LPV exposure.

©2002 9th Conference on Retroviruses and Opportunistic Infections