Antiviral Activity, Safety, and Pharmacokinetics of Bictegravir as 10-Day Monotherapy in HIV-1–Infected Adults. (1st May 2017)

• Record Type: Journal Article
• Authors: Gallant, Joel E.; Thompson, Melanie; DeJesus, Edwin; Voskuhl, Gene W.; Wei, Xuelian; Zhang, Heather; White, Kirsten; Cheng, Andrew; Quirk, Erin; Martin, Hal
• Is Part Of: Journal of acquired immune deficiency syndromes. Volume 75:Number 1(2017)
• Publication Date: 2017-05-01
• Subjects: antiretroviral therapy -- integrase strand transfer inhibitors -- pharmacokinetics -- bictegravir -- integrase inhibitors -- GS-9883; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome -- Periodicals; AIDS (Disease); Periodicals; 616.9792005
• DOI: 10.1097/QAI.0000000000001306
• Languages: English
• ISSNs: 1525-4135

Abstract

Abstract : 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.