title: Antiviral activity, pharmacokinetics, and safety of the HIV-1 protease inhibitor TMC310911, coadministered with ritonavir, in treatment-naive HIV-1-infected patients.
abstract: OBJECTIVE
  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 (log10 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 log10 copies/mL decrease in plasma HIV-1 RNA) at all evaluated doses, and treatment was generally safe and well tolerated.
authors.affiliation: *ICH Study Center, Hamburg, Germany; †EPIMED, Vivantes Auguste-Viktoria Klinikum, Berlin, Germany; ‡Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany; §Goethe-University Hospital/Medical Center-Infectious Diseases-Unit, Frankfurt, Germany; ‖Research and Early Development Department, Janssen Infectious Diseases BVBA, Beerse, Belgium; ¶Department of General Practice, Katholieke Universiteit Leuven, Leuven, Belgium; and #Department of Infectious Diseases, Janssen Research & Development, High Wycombe, Buckinghamshire, United Kingdom.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Stellbrink
authors.forename: Keikawus
authors.initials: K
authors.lastname: Arastéh
authors.forename: Dirk
authors.initials: D
authors.lastname: Schürmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Stephan
authors.forename: Inge
authors.initials: I
authors.lastname: Dierynck
authors.forename: Ilham
authors.initials: I
authors.lastname: Smyej
authors.forename: Richard M W
authors.initials: RM
authors.lastname: Hoetelmans
authors.forename: Carla
authors.initials: C
authors.lastname: Truyers
authors.forename: Paul
authors.initials: P
authors.lastname: Meyvisch
authors.forename: Bert
authors.initials: B
authors.lastname: Jacquemyn
authors.forename: Kris
authors.initials: K
authors.lastname: Mariën
authors.forename: Kenneth
authors.initials: K
authors.lastname: Simmen
authors.forename: René
authors.initials: R
authors.lastname: Verloes
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001769:Blood / Q000821:virology; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D019438:Ritonavir