Antiviral Activity, Safety, and Pharmacokinetics of Bictegravir as 10-Day Monotherapy in HIV-1-Infected Adults
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...
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| Published in: | Journal of acquired immune deficiency syndromes (1999) Vol. 75; no. 1; pp. 61 - 66 |
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| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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01.05.2017
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| ISSN: | 1944-7884 |
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| 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. |
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| AbstractList | 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. OBJECTIVETo evaluate antiviral activity, safety, and pharmacokinetics of short-term monotherapy with bictegravir (BIC), a novel, potent HIV integrase strand transfer inhibitor (INSTI).DESIGNPhase 1b, randomized, double-blinded, adaptive, sequential cohort, placebo-controlled study.METHODSHIV-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.RESULTSTwenty 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.CONCLUSIONSBIC 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. |
| Author | Gallant, Joel E DeJesus, Edwin Zhang, Heather Cheng, Andrew Voskuhl, Gene W White, Kirsten Martin, Hal Wei, Xuelian Quirk, Erin Thompson, Melanie |
| Author_xml | – sequence: 1 givenname: Joel E surname: Gallant fullname: Gallant, Joel E organization: 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 – sequence: 2 givenname: Melanie surname: Thompson fullname: Thompson, Melanie – sequence: 3 givenname: Edwin surname: DeJesus fullname: DeJesus, Edwin – sequence: 4 givenname: Gene W surname: Voskuhl fullname: Voskuhl, Gene W – sequence: 5 givenname: Xuelian surname: Wei fullname: Wei, Xuelian – sequence: 6 givenname: Heather surname: Zhang fullname: Zhang, Heather – sequence: 7 givenname: Kirsten surname: White fullname: White, Kirsten – sequence: 8 givenname: Andrew surname: Cheng fullname: Cheng, Andrew – sequence: 9 givenname: Erin surname: Quirk fullname: Quirk, Erin – sequence: 10 givenname: Hal surname: Martin fullname: Martin, Hal |
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| Snippet | To evaluate antiviral activity, safety, and pharmacokinetics of short-term monotherapy with bictegravir (BIC), a novel, potent HIV integrase strand transfer... OBJECTIVETo evaluate antiviral activity, safety, and pharmacokinetics of short-term monotherapy with bictegravir (BIC), a novel, potent HIV integrase strand... |
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| Title | Antiviral Activity, Safety, and Pharmacokinetics of Bictegravir as 10-Day Monotherapy in HIV-1-Infected Adults |
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