JAC Advance Access published online on February 18, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn050
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Original research |
Pharmacokinetics and short-term efficacy of a double-boosted protease inhibitor regimen in treatment-naive HIV-1-infected adults
1 HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center Bangkok, 104 Ratchadamri Road, Pathumwan, Bangkok 10330, Thailand 2 International Antiretroviral Therapy Evaluation Center, Pietersbergweg 9, 1105 BM Amsterdam, The Netherlands 3 National Center in HIV Epidemiology and Clinical Research, University of New South Wales, Level 2, 376 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia 4 Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands 5 Department of Medicine, Faculty of Medicine, Chulalongkorn University, 104 Ratchadamri Road, Pathumwan, Bangkok 10330, Thailand 6 Radboud University Nijmegen Medical Center, 864 Department of Clinical Pharmacy and Nijmegen University Centre for Infectious Diseases (NUCI), Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands
Received 6 November 2007; returned 5 December 2007; revised 27 December 2007; accepted 20 January 2008
* Correspondence address. HIV-NAT, Thai Red Cross AIDS Research Centre, 104 Rajdumri Road, Pathumwan, Bangkok 10330, Thailand. Tel: +66-2-652-3040, ext. 128; Fax: +66-2-254-7574/+66-2-252-5779; E-mail: jasper.v{at}hivnat.org
Objectives: To study the pharmacokinetics and short-term efficacy of low and standard dose lopinavir/ritonavir and saquinavir combinations in Thai, human immunodeficiency virus (HIV)-infected, treatment-naive patients.
Methods: In this open-label, 24-week, prospective study, 48 treatment-naive patients were randomized to lopinavir/ritonavir 400/100 mg+saquinavir 1000 mg twice daily (arm A), lopinavir/ritonavir 400/100 mg+saquinavir 600 mg twice daily (arm B), lopinavir/ritonavir 266/66 mg+saquinavir 1000 mg twice daily (arm C), or lopinavir/ritonavir 266/66 mg+saquinavir 600 mg twice daily (arm D). A 12 h. pharmacokinetic profile in all patients was performed. Plasma concentrations of saquinavir and lopinavir were determined using an HPLC technique. HIV-1 RNA was measured over 24 weeks.
Results: Forty-three subjects were included in the pharmacokinetic analysis. The total exposure differed significantly for the different arms. Median values for lopinavir area under the curve at 0–12 h were 128.2, 119.2, 66.1 and 68.5 mg·h/L for arms A–D, respectively. For saquinavir, the median values were 36.9, 19.2, 25.3 and 12.4 mg·h/L for arms A–D, respectively. The proportion of patients having a viral load below 50 copies/mL at week 24 was 39% for arm A, 63% for arm B, 55.0% for arm C, and 69% for arm D.
Conclusions: The pharmacokinetic parameters for the different treatment arms were adequate. However, the proportion of subjects with an undectable viral load at week 24 was lower than anticipated.
Key Words: viral dynamics , lopinavir , efficacy , dose reduction , saquinavir
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