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Joseph Gathe - One of the best experts on this subject based on the ideXlab platform.

  • Week 48 Results of EMERALD: A Phase 3, Randomized, Non-inferiority Study Evaluating the Efficacy and Safety of Switching from Boosted-protease Inhibitors (bPI) Plus Emtricitabine (FTC)/Tenofovir Disoproxil Fumarate (TDF) Regimens to the Once Daily (Q
    Open Forum Infectious Diseases, 2017
    Co-Authors: Chloe Orkin, Jean-michel Molina, Joel E. Gallant, Eugenia Negredo, Joseph Gathe, Joseph J. Eron, Erika Van Landuyt, Erkki Lathouwers, Veerle Hufkens, Romana Petrovic
    Abstract:

    Abstract Background EMERALD is evaluating the efficacy and safety of switching from bPI + FTC/TDF regimens (control) to D/C/F/TAF 800/150/200/10 mg in virologically suppressed, HIV-1-infected adults. We present Week 48 primary results. Method EMERALD (NCT02269917) is a randomized, active-controlled, open-label, international, multicenter, parallel-group, non-inferiority trial. Virologically suppressed (viral load [VL] < 50 c/mL for ≥2 months), HIV-1-infected adults were randomized (2:1) to switch to D/C/F/TAF or continue control. The FDA-stipulated primary endpoint was non-inferiority of D/C/F/TAF vs. control regarding % virologic rebound (confirmed VL ≥ 50 c/mL or premature discontinuations with last VL ≥ 50 c/mL) cumulative through Week 48 (4% margin). Result 1141 patients were randomized and treated (N = 763 D/C/F/TAF; N = 378 control); median age 46; 18% women; 76% white; 58% on >2 previous ARVs (prior to screening regimen); 15% with previous non-DRV virologic failure (VF). Virologic rebound through Week 48 was non-inferior for D/C/F/TAF (2.5%; n = 19) vs. control (2.1%; n = 8) (Δ0.4%, 95% CI: –1.5%; 2.2%; P < 0.001). Most rebounders (12/19 [63%] vs. 4/8 [50%]) resuppressed by Week 48 without change in therapy. Week 48 virologic suppression rates (VL < 50 c/mL; FDA Snapshot) were 94.9% vs. 93.7% (Δ1.2%, 95% CI: −1.7%;4.1%) and VF rates (VL ≥ 50 c/mL; Snapshot) were 0.8% vs. 0.5% (Δ0.3%, 95% CI: −0.7%;1.2%), with no discontinuations for VF. No resistance-associated mutations related to any study drug were observed. Adverse events (AEs) were similar between arms: AE-related discontinuations (1.4% vs. 1.3%); grade 3–4 AEs (6.8% vs. 8.2%); serious AEs (4.6% vs. 4.8%); and no deaths. Renal and bone parameters favored D/C/F/TAF vs. control. TC and LDL-C slightly favored control vs. D/C/F/TAF, with no clinically significant difference in TC/HDL-C ratio between arms (Table 1). Conclusion Percentage of virologic rebound after switching to D/C/F/TAF was non-inferior to control cumulative through Week 48, with high suppression rates (94.9%), no resistance development, better bone and renal safety parameters and similar TC/HDL-C ratio. D/C/F/TAF maintains the high genetic barrier to resistance of darunavir with the safety advantages of TAF, even in patients with a history of non-DRV VF. Disclosures C. Orkin, Janssen Pharmaceuticals: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker Honorarium and Travel bursary to attend conference. MSD: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker Honorarium and Travel bursary to attend conference. Viiv Healthcare: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker Honorarium and Travel bursary to attend conference. Gilead Sciences: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker Honorarium and Travel bursary to attend conference. J. M. Molina, Merck / Gilead: Scientific Advisor, Research grant. Janssen / Viiv / BMS / Teva: Scientific Advisor, Speaker Honorarium. Gilead: Speaker’s Bureau, Speaker Honorarium. J. Gallant, Janssen Therapeutics: Investigator, Research support. E. Negredo, Janssen: Board Member, Scientific Advisor and Speaker’s Bureau, Speaker Honorarium. J. Gathe, Janssen: Consultant and Investigator, Research grant and Speaker Honorarium. J. Eron, Janssen: Consultant and Grant Investigator, Consulting fee and Grant recipient. E. Van Landuyt, Janssen: Employee and Shareholder, Salary. E. Lathouwers, Janssen: Employee and Shareholder, Salary. V. Hufkens, Janssen: Employee and Shareholder, Salary. R. Petrovic, Janssen: Employee and Shareholder, Salary. M. Opsomer, Janssen: Employee and Shareholder, Salary.

  • Efficacy and Safety of Tenofovir Alafenamide vs. Tenofovir Disoproxil Fumarate in HIV-infected, Virologically Suppressed Black and Non-Blacks Adults Through Week 96: Subgroup Analysis of a Randomized Switch Study.
    Open Forum Infectious Diseases, 2017
    Co-Authors: Jason Flamm, Joseph Gathe, Thanes Vanig, Clifford Kinder, Michael F. Para, Bruce Rashbaum, Sorana Segal-maurer, David Shamblaw, Michael Wohlfeiler, Benjamin Young
    Abstract:

    Abstract Background Black adults are disproportionately affected by HIV. Methods We conducted a 96-week subgroup analysis by race (Black vs. non-Black) for efficacy (pre-specified) and safety (post-hoc) from a randomized, double blind, active-controlled study in virologically suppressed HIV-infected individuals who switched to emtricitabine/tenofovir alafenamide (FTC/TAF) from FTC/tenofovir disoproxil fumarate (FTC/TDF) vs. continuing FTC/TDF while remaining on the same third agent. Results Of 663 treated patients, 136 (20.5%) self-identified as Black (FTC /TAF 
n = 69, FTC /TDF n = 67). Baseline viral load, CD4 counts, renal laboratory parameters, and bone mineral density (BMD) were similar between the two arms within Blacks and non-Blacks. For Blacks, virologic success by FDA snapshot algorithm at week 96: FTC /TAF 87.0% vs. FTC /TDF 88.1%; for non-Blacks 89.0% vs. 89.7%. Few participants discontinued study drug due to adverse events in either subgroups (FTC/TAF vs. FTC/TDF: Black 0 vs.. 1.5%; non-Black, 3.0% vs. 1.1%). In assessment of renal and bone safety using estimated glomerular filtration rate (eGFR), renal biomarkers, and BMD, there were differences between two arms that generally favored FTC/TAF over FTC/TDF (Table). In the overall population, no cases of Fanconi syndrome or proximal renal tubulopathy occurred with FTC/TAF; one FTC/TDF participant discontinued study drug due to proximal tubulopathy. Conclusion In virologically suppressed Black adults, FTC/TAF demonstrated improvements in renal and bone safety over FTC/TDF with similar sustained efficacy at week 96. These results support switching to FTC/TAF from FTC/TDF for the treatment of HIV-1 infection in Black adults. Disclosures J. A. Flamm, Gilead: Investigator, Research support; T. Vanig, Gilead: Consultant, Investigator and Speaker’s Bureau, Consulting fee, Research support and Speaker Honorarium; J. Gathe, Gilead: Investigator, Research support; C. Kinder, Gilead: Investigator, Research support; M. Para, Gilead: Investigator, Research grant and Research support; B. Rashbaum, Gilead: Investigator and Shareholder, Research support and Speaker Honorarium; S. Segal-Maurer, Gilead Sciences: Consultant, Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker Honorarium; Janssen Therapeutics: Speaker’s Bureau, Speaker Honorarium; D. Shamblaw, Gilead: Investigator, Research support; M. Wohlfeiler, Gilead: Investigator, Research support; B. Young, Gilead Sciences: Independent Contractor, Investigator, Research Contractor and Scientific Advisor, Consulting fee, Research support and Speaker Honorarium; Merck & Co: Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker Honorarium; ViiV Healthcare: Scientific Advisor, Research grant; C. Zurawski, Gilead: Investigator, Research grant; M. S. Rhee, Gilead: Employee and Shareholder, Salary

Benjamin Young - One of the best experts on this subject based on the ideXlab platform.

  • Efficacy and Safety of Tenofovir Alafenamide vs. Tenofovir Disoproxil Fumarate in HIV-infected, Virologically Suppressed Black and Non-Blacks Adults Through Week 96: Subgroup Analysis of a Randomized Switch Study.
    Open Forum Infectious Diseases, 2017
    Co-Authors: Jason Flamm, Joseph Gathe, Thanes Vanig, Clifford Kinder, Michael F. Para, Bruce Rashbaum, Sorana Segal-maurer, David Shamblaw, Michael Wohlfeiler, Benjamin Young
    Abstract:

    Abstract Background Black adults are disproportionately affected by HIV. Methods We conducted a 96-week subgroup analysis by race (Black vs. non-Black) for efficacy (pre-specified) and safety (post-hoc) from a randomized, double blind, active-controlled study in virologically suppressed HIV-infected individuals who switched to emtricitabine/tenofovir alafenamide (FTC/TAF) from FTC/tenofovir disoproxil fumarate (FTC/TDF) vs. continuing FTC/TDF while remaining on the same third agent. Results Of 663 treated patients, 136 (20.5%) self-identified as Black (FTC /TAF 
n = 69, FTC /TDF n = 67). Baseline viral load, CD4 counts, renal laboratory parameters, and bone mineral density (BMD) were similar between the two arms within Blacks and non-Blacks. For Blacks, virologic success by FDA snapshot algorithm at week 96: FTC /TAF 87.0% vs. FTC /TDF 88.1%; for non-Blacks 89.0% vs. 89.7%. Few participants discontinued study drug due to adverse events in either subgroups (FTC/TAF vs. FTC/TDF: Black 0 vs.. 1.5%; non-Black, 3.0% vs. 1.1%). In assessment of renal and bone safety using estimated glomerular filtration rate (eGFR), renal biomarkers, and BMD, there were differences between two arms that generally favored FTC/TAF over FTC/TDF (Table). In the overall population, no cases of Fanconi syndrome or proximal renal tubulopathy occurred with FTC/TAF; one FTC/TDF participant discontinued study drug due to proximal tubulopathy. Conclusion In virologically suppressed Black adults, FTC/TAF demonstrated improvements in renal and bone safety over FTC/TDF with similar sustained efficacy at week 96. These results support switching to FTC/TAF from FTC/TDF for the treatment of HIV-1 infection in Black adults. Disclosures J. A. Flamm, Gilead: Investigator, Research support; T. Vanig, Gilead: Consultant, Investigator and Speaker’s Bureau, Consulting fee, Research support and Speaker Honorarium; J. Gathe, Gilead: Investigator, Research support; C. Kinder, Gilead: Investigator, Research support; M. Para, Gilead: Investigator, Research grant and Research support; B. Rashbaum, Gilead: Investigator and Shareholder, Research support and Speaker Honorarium; S. Segal-Maurer, Gilead Sciences: Consultant, Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker Honorarium; Janssen Therapeutics: Speaker’s Bureau, Speaker Honorarium; D. Shamblaw, Gilead: Investigator, Research support; M. Wohlfeiler, Gilead: Investigator, Research support; B. Young, Gilead Sciences: Independent Contractor, Investigator, Research Contractor and Scientific Advisor, Consulting fee, Research support and Speaker Honorarium; Merck & Co: Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker Honorarium; ViiV Healthcare: Scientific Advisor, Research grant; C. Zurawski, Gilead: Investigator, Research grant; M. S. Rhee, Gilead: Employee and Shareholder, Salary

Jean-michel Molina - One of the best experts on this subject based on the ideXlab platform.

  • Phase 3 Randomized, Controlled Trial of Switching to Fixed-dose Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) from Boosted Protease Inhibitor-based Regimens in Virologically Suppressed Adults: Week 48 Results
    Open Forum Infectious Diseases, 2017
    Co-Authors: Eric S. Daar, Edwin Dejesus, Peter Ruane, Gordon Crofoot, Godson Oguchi, Catherine Creticos, Jürgen K. Rockstroh, Jean-michel Molina, Ellen Koenig, Ya-pei Liu
    Abstract:

    Abstract Background Boosted protease inhibitor regimens (bPIs) are effective and often used in HIV-infected individuals with difficulties with adherence, but they can have drug–drug interactions and GI adverse effects. Bictegravir (B), a novel, potent integrase strand transfer inhibitor with a high barrier to resistance and low potential for drug–drug interactions, was coformulated with the recommended nucleoside reverse transcriptase inhibitor backbone emtricitabine (FTC)/tenofovir alafenamide (F/TAF) and demonstrated high efficacy and tolerability in randomized studies in treatment-naïve adults. This randomized Phase 3 study assesses efficacy and safety of switching to B/F/TAF from a multi-tablet regimen containing a bPI. Methods HIV-infected adults suppressed on regimens of boosted atazanavir (ATV) or darunavir (DRV) + abacavir/lamivudine (ABC/3TC) or FTC/tenofovir disoproxil fumarate (TDF) were randomized 1:1 to continue their current bPI regimen or switch to open-label coformulated B/F/TAF (50/200/25 mg) once daily. Primary endpoint was proportion with HIV-1 RNA ≥50 copies/mL (c/mL) at W48 (FDA snapshot). Noninferiority was assessed through 95.002% confidence intervals (CI) using a margin of 4%. Secondary endpoints included proportion with HIV-1 RNA <50 c/mL and safety measures at W48. Results A total of 577 participants were randomized and treated with B/F/TAF (n = 290) or current bPI regimens (n = 287): 17% women, 26% Black, median age 48 years. Most were receiving a bPI with FTC/TDF (85%) at screening. At W48, switching to B/F/TAF was noninferior to continuing bPI with 1.7% in each group having HIV-1 RNA ≥50 c/mL (difference −0.0%; 95.002% CI −2.5% to 2.5%, P = 1.00); the proportion with HIV-1 RNA <50 c/mL was 92.1% in B/F/TAF vs. 88.9% in bPI. No participant on B/F/TAF developed resistance to study drugs. One participant on DRV/ritonavir + ABC/3TC developed a treatment-emergent L74V mutation. Incidence of grade 3 or 4 AEs was similar (B/F/TAF 4%, bPI regimens 6%). No renal discontinuations or tubulopathy cases occurred with B/F/TAF. Conclusion Adults switching to B/F/TAF from a boosted PI maintained high rates of virologic suppression without resistance. B/F/TAF was safe and well tolerated. Disclosures E. Daar, Bristol-Myers Squibb: Consultant, Consulting fee. Gilead Sciences, Inc.: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support. Janssen: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support. Merck: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support. Teva Pharmaceuticals: Consultant and Scientific Advisor, Consulting fee. ViiV: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support. E. DeJesus, Abbott Laboratories; Achillion Pharmaceuticals, Avexa, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Hoffmann LaRoche, Idenix, Janssen, Merck, Pfizer, Sangamo, Taimed, Tobira, and Vertex: Grant Investigator, Research grant. Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and Vertex: Scientific Advisor, Consulting fee. P. Ruane, Gilead: Investigator, Scientific Advisor and Shareholder, Consulting fee and Research support. Merck: Speaker’s Bureau, Speaker Honorarium. Boehringer: Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker Honorarium. Janssen: Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker Honorarium. Abbott: Investigator, Scientific Advisor and Speaker’s Bureau, Research support and Speaker Honorarium. Idenix: Investigator, Research support. ViiV: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker Honorarium. BMS: Consultant, Investigator and Speaker’s Bureau, Consulting fee, Research support and Speaker Honorarium. G. Crofoot, Gilead: Investigator and Scientific Advisor, Advisory Honorarium and Research grant. ViiV: Investigator and Scientific Advisor, Advisory Honorarium, Research grant and Research support. C. Creticos, Thera Technologies and ViiV Healthcare: Scientific Advisor, Consulting fee. Gilead sciences, Merck, and ViiV Healthcare: Investigator, Research support. Pfizer: Speaker’s Bureau, Speaker Honorarium. J. K. Rockstroh, Abbvie: Consultant and Investigator, Consulting fee and Speaker Honorarium. Gilead: Consultant, Investigator and Scientific Advisor, Consulting fee and Speaker Honorarium. ViiV: Scientific Advisor, Consulting fee. Janssen: Investigator and Speaker at educational event, Speaker Honorarium. J. M. Molina, Gilead, ViiV, Merck, Janssen, BMS and TEVA: Scientific Advisor, Speaker Honorarium. Y. P. Liu, Gilead: Employee and Shareholder, Salary and Shareholder. K. Andreatta, Gilead: Employee and Shareholder, Salary and Shareholder. H. Graham, Gilead Sciences: Employee and Shareholder, Salary. A. Cheng, Gilead: Employee and Shareholder, Salary. H. Martin, Gilead Sciences: Employee, Salary. E. Quirk, Gilead: Employee and Shareholder, Salary

  • Week 48 Results of EMERALD: A Phase 3, Randomized, Non-inferiority Study Evaluating the Efficacy and Safety of Switching from Boosted-protease Inhibitors (bPI) Plus Emtricitabine (FTC)/Tenofovir Disoproxil Fumarate (TDF) Regimens to the Once Daily (Q
    Open Forum Infectious Diseases, 2017
    Co-Authors: Chloe Orkin, Jean-michel Molina, Joel E. Gallant, Eugenia Negredo, Joseph Gathe, Joseph J. Eron, Erika Van Landuyt, Erkki Lathouwers, Veerle Hufkens, Romana Petrovic
    Abstract:

    Abstract Background EMERALD is evaluating the efficacy and safety of switching from bPI + FTC/TDF regimens (control) to D/C/F/TAF 800/150/200/10 mg in virologically suppressed, HIV-1-infected adults. We present Week 48 primary results. Method EMERALD (NCT02269917) is a randomized, active-controlled, open-label, international, multicenter, parallel-group, non-inferiority trial. Virologically suppressed (viral load [VL] < 50 c/mL for ≥2 months), HIV-1-infected adults were randomized (2:1) to switch to D/C/F/TAF or continue control. The FDA-stipulated primary endpoint was non-inferiority of D/C/F/TAF vs. control regarding % virologic rebound (confirmed VL ≥ 50 c/mL or premature discontinuations with last VL ≥ 50 c/mL) cumulative through Week 48 (4% margin). Result 1141 patients were randomized and treated (N = 763 D/C/F/TAF; N = 378 control); median age 46; 18% women; 76% white; 58% on >2 previous ARVs (prior to screening regimen); 15% with previous non-DRV virologic failure (VF). Virologic rebound through Week 48 was non-inferior for D/C/F/TAF (2.5%; n = 19) vs. control (2.1%; n = 8) (Δ0.4%, 95% CI: –1.5%; 2.2%; P < 0.001). Most rebounders (12/19 [63%] vs. 4/8 [50%]) resuppressed by Week 48 without change in therapy. Week 48 virologic suppression rates (VL < 50 c/mL; FDA Snapshot) were 94.9% vs. 93.7% (Δ1.2%, 95% CI: −1.7%;4.1%) and VF rates (VL ≥ 50 c/mL; Snapshot) were 0.8% vs. 0.5% (Δ0.3%, 95% CI: −0.7%;1.2%), with no discontinuations for VF. No resistance-associated mutations related to any study drug were observed. Adverse events (AEs) were similar between arms: AE-related discontinuations (1.4% vs. 1.3%); grade 3–4 AEs (6.8% vs. 8.2%); serious AEs (4.6% vs. 4.8%); and no deaths. Renal and bone parameters favored D/C/F/TAF vs. control. TC and LDL-C slightly favored control vs. D/C/F/TAF, with no clinically significant difference in TC/HDL-C ratio between arms (Table 1). Conclusion Percentage of virologic rebound after switching to D/C/F/TAF was non-inferior to control cumulative through Week 48, with high suppression rates (94.9%), no resistance development, better bone and renal safety parameters and similar TC/HDL-C ratio. D/C/F/TAF maintains the high genetic barrier to resistance of darunavir with the safety advantages of TAF, even in patients with a history of non-DRV VF. Disclosures C. Orkin, Janssen Pharmaceuticals: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker Honorarium and Travel bursary to attend conference. MSD: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker Honorarium and Travel bursary to attend conference. Viiv Healthcare: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker Honorarium and Travel bursary to attend conference. Gilead Sciences: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker Honorarium and Travel bursary to attend conference. J. M. Molina, Merck / Gilead: Scientific Advisor, Research grant. Janssen / Viiv / BMS / Teva: Scientific Advisor, Speaker Honorarium. Gilead: Speaker’s Bureau, Speaker Honorarium. J. Gallant, Janssen Therapeutics: Investigator, Research support. E. Negredo, Janssen: Board Member, Scientific Advisor and Speaker’s Bureau, Speaker Honorarium. J. Gathe, Janssen: Consultant and Investigator, Research grant and Speaker Honorarium. J. Eron, Janssen: Consultant and Grant Investigator, Consulting fee and Grant recipient. E. Van Landuyt, Janssen: Employee and Shareholder, Salary. E. Lathouwers, Janssen: Employee and Shareholder, Salary. V. Hufkens, Janssen: Employee and Shareholder, Salary. R. Petrovic, Janssen: Employee and Shareholder, Salary. M. Opsomer, Janssen: Employee and Shareholder, Salary.

Romana Petrovic - One of the best experts on this subject based on the ideXlab platform.

  • Week 48 Results of EMERALD: A Phase 3, Randomized, Non-inferiority Study Evaluating the Efficacy and Safety of Switching from Boosted-protease Inhibitors (bPI) Plus Emtricitabine (FTC)/Tenofovir Disoproxil Fumarate (TDF) Regimens to the Once Daily (Q
    Open Forum Infectious Diseases, 2017
    Co-Authors: Chloe Orkin, Jean-michel Molina, Joel E. Gallant, Eugenia Negredo, Joseph Gathe, Joseph J. Eron, Erika Van Landuyt, Erkki Lathouwers, Veerle Hufkens, Romana Petrovic
    Abstract:

    Abstract Background EMERALD is evaluating the efficacy and safety of switching from bPI + FTC/TDF regimens (control) to D/C/F/TAF 800/150/200/10 mg in virologically suppressed, HIV-1-infected adults. We present Week 48 primary results. Method EMERALD (NCT02269917) is a randomized, active-controlled, open-label, international, multicenter, parallel-group, non-inferiority trial. Virologically suppressed (viral load [VL] < 50 c/mL for ≥2 months), HIV-1-infected adults were randomized (2:1) to switch to D/C/F/TAF or continue control. The FDA-stipulated primary endpoint was non-inferiority of D/C/F/TAF vs. control regarding % virologic rebound (confirmed VL ≥ 50 c/mL or premature discontinuations with last VL ≥ 50 c/mL) cumulative through Week 48 (4% margin). Result 1141 patients were randomized and treated (N = 763 D/C/F/TAF; N = 378 control); median age 46; 18% women; 76% white; 58% on >2 previous ARVs (prior to screening regimen); 15% with previous non-DRV virologic failure (VF). Virologic rebound through Week 48 was non-inferior for D/C/F/TAF (2.5%; n = 19) vs. control (2.1%; n = 8) (Δ0.4%, 95% CI: –1.5%; 2.2%; P < 0.001). Most rebounders (12/19 [63%] vs. 4/8 [50%]) resuppressed by Week 48 without change in therapy. Week 48 virologic suppression rates (VL < 50 c/mL; FDA Snapshot) were 94.9% vs. 93.7% (Δ1.2%, 95% CI: −1.7%;4.1%) and VF rates (VL ≥ 50 c/mL; Snapshot) were 0.8% vs. 0.5% (Δ0.3%, 95% CI: −0.7%;1.2%), with no discontinuations for VF. No resistance-associated mutations related to any study drug were observed. Adverse events (AEs) were similar between arms: AE-related discontinuations (1.4% vs. 1.3%); grade 3–4 AEs (6.8% vs. 8.2%); serious AEs (4.6% vs. 4.8%); and no deaths. Renal and bone parameters favored D/C/F/TAF vs. control. TC and LDL-C slightly favored control vs. D/C/F/TAF, with no clinically significant difference in TC/HDL-C ratio between arms (Table 1). Conclusion Percentage of virologic rebound after switching to D/C/F/TAF was non-inferior to control cumulative through Week 48, with high suppression rates (94.9%), no resistance development, better bone and renal safety parameters and similar TC/HDL-C ratio. D/C/F/TAF maintains the high genetic barrier to resistance of darunavir with the safety advantages of TAF, even in patients with a history of non-DRV VF. Disclosures C. Orkin, Janssen Pharmaceuticals: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker Honorarium and Travel bursary to attend conference. MSD: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker Honorarium and Travel bursary to attend conference. Viiv Healthcare: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker Honorarium and Travel bursary to attend conference. Gilead Sciences: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker Honorarium and Travel bursary to attend conference. J. M. Molina, Merck / Gilead: Scientific Advisor, Research grant. Janssen / Viiv / BMS / Teva: Scientific Advisor, Speaker Honorarium. Gilead: Speaker’s Bureau, Speaker Honorarium. J. Gallant, Janssen Therapeutics: Investigator, Research support. E. Negredo, Janssen: Board Member, Scientific Advisor and Speaker’s Bureau, Speaker Honorarium. J. Gathe, Janssen: Consultant and Investigator, Research grant and Speaker Honorarium. J. Eron, Janssen: Consultant and Grant Investigator, Consulting fee and Grant recipient. E. Van Landuyt, Janssen: Employee and Shareholder, Salary. E. Lathouwers, Janssen: Employee and Shareholder, Salary. V. Hufkens, Janssen: Employee and Shareholder, Salary. R. Petrovic, Janssen: Employee and Shareholder, Salary. M. Opsomer, Janssen: Employee and Shareholder, Salary.

Ya-pei Liu - One of the best experts on this subject based on the ideXlab platform.

  • Phase 3 Randomized, Controlled Trial of Switching to Fixed-dose Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) from Boosted Protease Inhibitor-based Regimens in Virologically Suppressed Adults: Week 48 Results
    Open Forum Infectious Diseases, 2017
    Co-Authors: Eric S. Daar, Edwin Dejesus, Peter Ruane, Gordon Crofoot, Godson Oguchi, Catherine Creticos, Jürgen K. Rockstroh, Jean-michel Molina, Ellen Koenig, Ya-pei Liu
    Abstract:

    Abstract Background Boosted protease inhibitor regimens (bPIs) are effective and often used in HIV-infected individuals with difficulties with adherence, but they can have drug–drug interactions and GI adverse effects. Bictegravir (B), a novel, potent integrase strand transfer inhibitor with a high barrier to resistance and low potential for drug–drug interactions, was coformulated with the recommended nucleoside reverse transcriptase inhibitor backbone emtricitabine (FTC)/tenofovir alafenamide (F/TAF) and demonstrated high efficacy and tolerability in randomized studies in treatment-naïve adults. This randomized Phase 3 study assesses efficacy and safety of switching to B/F/TAF from a multi-tablet regimen containing a bPI. Methods HIV-infected adults suppressed on regimens of boosted atazanavir (ATV) or darunavir (DRV) + abacavir/lamivudine (ABC/3TC) or FTC/tenofovir disoproxil fumarate (TDF) were randomized 1:1 to continue their current bPI regimen or switch to open-label coformulated B/F/TAF (50/200/25 mg) once daily. Primary endpoint was proportion with HIV-1 RNA ≥50 copies/mL (c/mL) at W48 (FDA snapshot). Noninferiority was assessed through 95.002% confidence intervals (CI) using a margin of 4%. Secondary endpoints included proportion with HIV-1 RNA <50 c/mL and safety measures at W48. Results A total of 577 participants were randomized and treated with B/F/TAF (n = 290) or current bPI regimens (n = 287): 17% women, 26% Black, median age 48 years. Most were receiving a bPI with FTC/TDF (85%) at screening. At W48, switching to B/F/TAF was noninferior to continuing bPI with 1.7% in each group having HIV-1 RNA ≥50 c/mL (difference −0.0%; 95.002% CI −2.5% to 2.5%, P = 1.00); the proportion with HIV-1 RNA <50 c/mL was 92.1% in B/F/TAF vs. 88.9% in bPI. No participant on B/F/TAF developed resistance to study drugs. One participant on DRV/ritonavir + ABC/3TC developed a treatment-emergent L74V mutation. Incidence of grade 3 or 4 AEs was similar (B/F/TAF 4%, bPI regimens 6%). No renal discontinuations or tubulopathy cases occurred with B/F/TAF. Conclusion Adults switching to B/F/TAF from a boosted PI maintained high rates of virologic suppression without resistance. B/F/TAF was safe and well tolerated. Disclosures E. Daar, Bristol-Myers Squibb: Consultant, Consulting fee. Gilead Sciences, Inc.: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support. Janssen: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support. Merck: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support. Teva Pharmaceuticals: Consultant and Scientific Advisor, Consulting fee. ViiV: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support. E. DeJesus, Abbott Laboratories; Achillion Pharmaceuticals, Avexa, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Hoffmann LaRoche, Idenix, Janssen, Merck, Pfizer, Sangamo, Taimed, Tobira, and Vertex: Grant Investigator, Research grant. Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and Vertex: Scientific Advisor, Consulting fee. P. Ruane, Gilead: Investigator, Scientific Advisor and Shareholder, Consulting fee and Research support. Merck: Speaker’s Bureau, Speaker Honorarium. Boehringer: Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker Honorarium. Janssen: Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker Honorarium. Abbott: Investigator, Scientific Advisor and Speaker’s Bureau, Research support and Speaker Honorarium. Idenix: Investigator, Research support. ViiV: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker Honorarium. BMS: Consultant, Investigator and Speaker’s Bureau, Consulting fee, Research support and Speaker Honorarium. G. Crofoot, Gilead: Investigator and Scientific Advisor, Advisory Honorarium and Research grant. ViiV: Investigator and Scientific Advisor, Advisory Honorarium, Research grant and Research support. C. Creticos, Thera Technologies and ViiV Healthcare: Scientific Advisor, Consulting fee. Gilead sciences, Merck, and ViiV Healthcare: Investigator, Research support. Pfizer: Speaker’s Bureau, Speaker Honorarium. J. K. Rockstroh, Abbvie: Consultant and Investigator, Consulting fee and Speaker Honorarium. Gilead: Consultant, Investigator and Scientific Advisor, Consulting fee and Speaker Honorarium. ViiV: Scientific Advisor, Consulting fee. Janssen: Investigator and Speaker at educational event, Speaker Honorarium. J. M. Molina, Gilead, ViiV, Merck, Janssen, BMS and TEVA: Scientific Advisor, Speaker Honorarium. Y. P. Liu, Gilead: Employee and Shareholder, Salary and Shareholder. K. Andreatta, Gilead: Employee and Shareholder, Salary and Shareholder. H. Graham, Gilead Sciences: Employee and Shareholder, Salary. A. Cheng, Gilead: Employee and Shareholder, Salary. H. Martin, Gilead Sciences: Employee, Salary. E. Quirk, Gilead: Employee and Shareholder, Salary