title: A randomized, double-blind, placebo-controlled, short-term monotherapy study of doravirine in treatment-naive HIV-infected individuals.
abstract: OBJECTIVE
  To assess the antiviral activity, pharmacokinetics, and safety of doravirine in nonnucleoside reverse transcriptase inhibitor-naïve, HIV-infected men.
  
  
  METHODS
  Double-blind, randomized, two-panel, dose-escalation study.
  
  
  METHODS
  In two sequential panels, 18 individuals received doravirine [25 mg (Panel A) or 200 mg (Panel B)] or matching placebo once daily for 7 days. Plasma samples were collected daily for measurement of HIV-1 RNA levels and doravirine pharmacokinetics.
  
  
  RESULTS
  For the mean change from baseline in HIV RNA (log10 copies/ml) at 24 h after the day 7 dose, the mean difference (90% confidence interval) between doravirine and placebo was -1.37 (-1.60, -1.14) in the 25-mg group and -1.26 (-1.51, -1.02) in the 200-mg group. None of the participants had viral breakthrough. Increases in mean AUC0-24 h, Cmax, and C24 h were slightly less than dose-proportional, with median Tmax of 1.0-2.0 h. Steady state was achieved after 3-5 days of once-daily dosing. At steady state, accumulation ratios (day 7/day 1) for AUC0-24 h, Cmax, and C24 h were 1.2-1.6. The calculated effective t1/2 (10-16 h) was similar to that in HIV-uninfected individuals. Adverse events were limited in number, transient, and generally mild to moderate in intensity. One participant had a serious adverse event of elevated liver enzymes (judged probably not drug related) in concurrence with a newly acquired hepatitis C infection.
  
  
  CONCLUSIONS
  Doravirine monotherapy demonstrated robust antiviral activity at both dose levels, without evidence of viral resistance, and was generally well tolerated. Doravirine pharmacokinetics in HIV-infected individuals were similar to those in uninfected individuals receiving similar doses in prior studies.
authors.affiliation: aDepartment of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin BerlinbCharité Research Organisation, Berlin, GermanycMerck & Co., Inc., Kenilworth, New Jersey, USAdMerck, Sharp & Dohme (Europe) Inc., Brussels, Belgium.*Current affiliation: Gilead Sciences, Seattle, Washington, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schürmann
authors.forename: Christian
authors.initials: C
authors.lastname: Sobotha
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Gilmartin
authors.forename: Martine
authors.initials: M
authors.lastname: Robberechts
authors.forename: Inge
authors.initials: I
authors.lastname: De Lepeleire
authors.forename: Ka Lai
authors.initials: KL
authors.lastname: Yee
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.forename: Rachael
authors.initials: R
authors.lastname: Liu
authors.forename: Frank
authors.initials: F
authors.lastname: Wagner
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
authors.forename: Joan R
authors.initials: JR
authors.lastname: Butterton
authors.forename: Matt S
authors.initials: MS
authors.lastname: Anderson
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D010949:Plasma / Q000737:chemistry / Q000821:virology; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics; D012367:RNA, Viral / Q000032:analysis; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D010919:Placebos; D011728:Pyridones; D012367:RNA, Viral; D014230:Triazoles; C000592662:doravirine