Antiviral Activity, Pharmacokinetics, and Safety of the HIV-1 Protease Inhibitor TMC310911, Coadministered With Ritonavir, in Treatment-Naive HIV-1-Infected Patients

作者：Stellbrink Hans Juergen; Arasteh Keikawus; Schuermann Dirk; Stephan Christoph; Dierynck Inge; Smyej Ilham; Hoetelmans Richard M W; Truyers Carla; Meyvisch Paul; Jacquemyn Bert; Marien Kris; Simmen Kenneth; Verloes Rene^*

来源：JAIDS: Journal of Acquired Immune Deficiency Syndromes , 2014, 65(3): 283-289.

DOI：10.1097/QAI.0000000000000003

• pharmacokinetics
• HIV-1 protease inhibitor
• ritonavir
• antiviral activity
• TMC310911
• antiretroviral therapy

Objectives: TMC310911 is a novel HIV type-1 (HIV-1) protease inhibitor with broad in vitro antiviral activity. In this phase 2a, open-label randomized study, the antiviral activity, pharmacokinetics, and safety and tolerability of ritonavir-boosted TMC310911 was assessed. Methods: In this study, treatment-naive HIV-1 patients (aged 18-60 years) received 1 of the 4 dosing regimens of TMC310911: 150 mg twice-daily (bid) (n = 8), 300 mg bid (n = 8), 75 mg bid (n = 9), or 300 mg once-daily (qd) (n = 8), for 14 days, all coadministered with 100 mg of ritonavir, as only antiretroviral therapy. Results: The mean change from baseline in HIV-1 RNA (log(10) copies per milliliter; primary efficacy endpoint) was -1.30 (75 mg bid), -1.14 (150 mg bid), -1.07 (300 mg bid), and -1.06 (300 mg qd) on day 8 and -1.53 (75 mg bid), -1.79 (150 mg bid), -1.69 (300 mg bid), and -1.55 (300 mg qd) on day 15. At steady state (day 14), the mean maximum plasma concentration and mean area under the plasma concentration-time curve from 0 to 12 hours tended to increase dose proportionally for bid doses; TMC310911 daily exposures for the 300 mg qd treatment and 150 mg bid treatment were comparable. The most common (>= 10%) treatment-emergent adverse events were fatigue (27.3%) and nausea (12.1%); no deaths or serious treatment-emergent adverse events were reported in this study. Conclusions: Combination treatment with TMC310911 and ritonavir showed potent antiviral activity (>1.5 log(10) copies/mL decrease in plasma HIV-1 RNA) at all evaluated doses, and treatment was generally safe and well tolerated.

• 出版日期2014-3-1