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Antimicrobial Agents and Chemotherapy, September 2007, p. 3264-3272, Vol. 51, No. 9
0066-4804/07/$08.00+0     doi:10.1128/AAC.00036-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Association of Saquinavir Plasma Concentrations with Side Effects but Not with Antiretroviral Outcome in Patients Infected with Protease Inhibitor-Susceptible Human Immunodeficiency Virus Type 1{triangledown}

Jörn Lötsch,1* Sebastian Harder,1 Martin Stürmer,2 Hans-Wilhelm Doerr,2 Gerd Geisslinger,1 Schlomo Staszewski,3 and Nils von Hentig1

pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goeth University, Theodor Stern Kai 7, D-60590 Frankfurt, Germany,1 Institute of Medical Virology/ZAFES, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany,2 Medical HIV Research and Treatment Unit, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany3

Received 11 January 2007/ Returned for modification 27 April 2007/ Accepted 11 June 2007

The objective of this study was to identify parameters among saquinavir pharmacokinetics, patients' demographics or comedications, to be addressed for improved personalized therapy. The presence of human immunodeficiency virus type 1 (HIV-1) RNA at therapy week 48 (principal target parameter), CD4 cell count at week 48, infections and side effects during 48 weeks, indicators of liver toxicity and lipid abnormalities at week 48, and a 12-h saquinavir plasma concentration-versus-time profile were assessed in 56 patients receiving saquinavir-ritonavir (1,000 and 100 mg, respectively) twice daily (44 therapy-naïve and 12 antiretrovirally pretreated patients) for association with saquinavir plasma concentrations, demographics, baseline values of target parameters, and coadministered antiretrovirals. Antiretroviral failure was observed in 8 of the 56 patients in whom HIV-1 RNA was detectable at week 48. This therapeutic failure was not associated with individual saquinavir pharmacokinetics. More likely, therapeutic failure was related to incidences interfering with antiretroviral therapy, causing therapy interruptions or incompliance. Weak associations were, however, seen between high maximum saquinavir plasma concentrations and both CD4 counts of ≥200 cells µl–1 at week 48 (P = 0.014) and constitutional side effects during 48 weeks (P = 0.002). However, patients with high CD4 counts and constitutional side effects were not identical (P = 0.53). Saquinavir therapeutic drug monitoring in patients infected with protease inhibitor-susceptible HIV-1 taking saquinavir-ritonavir (1,000 and 100 mg, respectively) is not demanded for improving the antiretroviral effect. It may be contemplated in cases with constitutional side effects or low CD4 counts with weak immune responses.

* Corresponding author. Mailing address: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany. Phone: 49-69-6301-4589. Fax: 49-69-6301-7636. E-mail: j.loetsch{at}em.uni-frankfurt.de

{triangledown} Published ahead of print on 18 June 2007.

Antimicrobial Agents and Chemotherapy, September 2007, p. 3264-3272, Vol. 51, No. 9
0066-4804/07/$08.00+0     doi:10.1128/AAC.00036-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • von Hentig, N., Lotsch, J. (2009). Cytochrome P450 3A Inhibition by Atazanavir and Ritonavir, but Not Demography or Drug Formulation, Influences Saquinavir Population Pharmacokinetics in Human Immunodeficiency Virus Type 1-Infected Adults. Antimicrob. Agents Chemother. 53: 3524-3527 [Abstract] [Full Text]  
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