title: Antiviral Activity, Safety, and Pharmacokinetics of Bictegravir as 10-Day Monotherapy in HIV-1-Infected Adults.
abstract: To evaluate antiviral activity, safety, and pharmacokinetics of short-term monotherapy with bictegravir (BIC), a novel, potent HIV integrase strand transfer inhibitor (INSTI).
  
  
  
  Phase 1b, randomized, double-blinded, adaptive, sequential cohort, placebo-controlled study.
  
  
  
  HIV-infected adults not taking antiretroviral therapy were randomized to receive BIC (5, 25, 50, or 100 mg) or placebo once daily for 10 days. Primary endpoint was time-weighted average change from baseline to day 11 (DAVG11) for plasma HIV-1 RNA. HIV-1 RNA, adverse events (AEs), and laboratory assessments were evaluated through day 17.
  
  
  
  Twenty participants were enrolled (n = 4/group). Mean DAVG11 ranged from -0.92 to -1.61 across BIC doses versus -0.01 for placebo. Significant reductions in plasma HIV-1 RNA from baseline at day 11 were observed for all BIC doses compared with placebo (P < 0.001); mean decreases were 1.45-2.43 log10 copies/mL. Increased BIC exposures correlated with increased reduction in plasma HIV-1 RNA from baseline on day 11. Three participants on BIC (50 or 100 mg) achieved plasma HIV-1 RNA <50 copies/mL by end of study. Median Tmax ranged from 1.0 to 1.8 hours (day 1, postdose) and 1.3-2.7 hours (day 10), with median t1/2 ranging from 15.9 to 20.9 hours. No participant developed primary INSTI-R substitution through day 17. BIC was well tolerated, with no discontinuations because of adverse events.
  
  
  
  BIC is a novel, potent, unboosted INSTI that demonstrated rapid, dose-dependent declines in HIV-1 RNA after 10 days of monotherapy. BIC was well tolerated, and displayed rapid absorption and a half-life supportive of once-daily therapy in HIV-infected subjects.
authors.affiliation: *Southwest CARE Center, Santa Fe, NM; †AIDS Research Consortium of Atlanta, Atlanta, GA; ‡Orlando Immunology Center, Orlando, FL; §AIDS Arms, Inc., Dallas, TX; and ‖Gilead Sciences, Inc., Foster City, CA.
authors.forename: Joel E
authors.initials: JE
authors.lastname: Gallant
authors.forename: Melanie
authors.initials: M
authors.lastname: Thompson
authors.forename: Edwin
authors.initials: E
authors.lastname: DeJesus
authors.forename: Gene W
authors.initials: GW
authors.lastname: Voskuhl
authors.forename: Xuelian
authors.initials: X
authors.lastname: Wei
authors.forename: Heather
authors.initials: H
authors.lastname: Zhang
authors.forename: Kirsten
authors.initials: K
authors.lastname: White
authors.forename: Andrew
authors.initials: A
authors.lastname: Cheng
authors.forename: Erin
authors.initials: E
authors.lastname: Quirk
authors.forename: Hal
authors.initials: H
authors.lastname: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000577:Amides; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D006575:Heterocyclic Compounds, 3-Ring; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D010919:Placebos / Q000008:administration & dosage; D010949:Plasma / Q000737:chemistry; D011728:Pyridones; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000577:Amides; D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D006576:Heterocyclic Compounds, 4 or More Rings; D010879:Piperazines; D010919:Placebos; D011728:Pyridones; D012367:RNA, Viral; C000620396:bictegravir