PMID- 28196003
OWN - NLM
STAT- MEDLINE
DCOM- 20170616
LR  - 20211204
IS  - 1944-7884 (Electronic)
IS  - 1525-4135 (Print)
IS  - 1525-4135 (Linking)
VI  - 75
IP  - 1
DP  - 2017 May 1
TI  - Antiviral Activity, Safety, and Pharmacokinetics of Bictegravir as 10-Day 
      Monotherapy in HIV-1-Infected Adults.
PG  - 61-66
LID - 10.1097/QAI.0000000000001306 [doi]
AB  - OBJECTIVE: To evaluate antiviral activity, safety, and pharmacokinetics of 
      short-term monotherapy with bictegravir (BIC), a novel, potent HIV integrase 
      strand transfer inhibitor (INSTI). DESIGN: Phase 1b, randomized, double-blinded, 
      adaptive, sequential cohort, placebo-controlled study. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
FAU - Gallant, Joel E
AU  - Gallant JE
AD  - *Southwest CARE Center, Santa Fe, NM; daggerAIDS Research Consortium of Atlanta, 
      Atlanta, GA; double daggerOrlando Immunology Center, Orlando, FL;  section signAIDS Arms, Inc., Dallas, 
      TX; and  ||Gilead Sciences, Inc., Foster City, CA.
FAU - Thompson, Melanie
AU  - Thompson M
FAU - DeJesus, Edwin
AU  - DeJesus E
FAU - Voskuhl, Gene W
AU  - Voskuhl GW
FAU - Wei, Xuelian
AU  - Wei X
FAU - Zhang, Heather
AU  - Zhang H
FAU - White, Kirsten
AU  - White K
FAU - Cheng, Andrew
AU  - Cheng A
FAU - Quirk, Erin
AU  - Quirk E
FAU - Martin, Hal
AU  - Martin H
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - United States
TA  - J Acquir Immune Defic Syndr
JT  - Journal of acquired immune deficiency syndromes (1999)
JID - 100892005
RN  - 0 (Amides)
RN  - 0 (HIV Integrase Inhibitors)
RN  - 0 (Heterocyclic Compounds, 3-Ring)
RN  - 0 (Heterocyclic Compounds, 4 or More Rings)
RN  - 0 (Piperazines)
RN  - 0 (Placebos)
RN  - 0 (Pyridones)
RN  - 0 (RNA, Viral)
RN  - 8GB79LOJ07 (bictegravir)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Amides
MH  - Double-Blind Method
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology
MH  - Female
MH  - HIV Infections/*drug therapy/virology
MH  - HIV Integrase Inhibitors/*administration & dosage/*adverse 
      effects/pharmacokinetics/pharmacology
MH  - HIV-1/*drug effects
MH  - Heterocyclic Compounds, 3-Ring
MH  - Heterocyclic Compounds, 4 or More Rings/*administration & dosage/*adverse 
      effects/pharmacokinetics/pharmacology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Piperazines
MH  - Placebos/administration & dosage
MH  - Plasma/chemistry
MH  - Pyridones
MH  - RNA, Viral/blood
MH  - Treatment Outcome
MH  - Viral Load
MH  - Young Adult
PMC - PMC5389589
COIS- X.W., H.Z., K.W., A.C., E.Q., and H.M., are employees of Gilead and hold stock 
      interest in the company. The remaining authors have no conflicts of interest to 
      disclose.
EDAT- 2017/02/15 06:00
MHDA- 2017/06/18 06:00
PMCR- 2017/04/12
CRDT- 2017/02/15 06:00
PHST- 2017/02/15 06:00 [pubmed]
PHST- 2017/06/18 06:00 [medline]
PHST- 2017/02/15 06:00 [entrez]
PHST- 2017/04/12 00:00 [pmc-release]
AID - QAIV17457 [pii]
AID - 10.1097/QAI.0000000000001306 [doi]
PST - ppublish
SO  - J Acquir Immune Defic Syndr. 2017 May 1;75(1):61-66. doi: 
      10.1097/QAI.0000000000001306.