Comparison of INSTI vs. INSTI QDMRK in Study GS-US-380-1489
This study, GS-US-380-1489, investigates the efficacy of BIC/F/TAF versus DTG/ABC/3TC in HIV patients. It analyzes virologic outcomes, baseline characteristics, and patient disposition at week 48. Results show non-inferiority of BIC/F/TAF in achieving HIV RNA suppression. Details on participant demographics, virologic outcomes, and resistance testing are provided.
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Comparison of INSTI vs INSTI QDMRK SPRING-2 ONCEMRK GS-US-380-1489 GS-US-380-1490
Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Design Randomisation* 1 : 1 Double-blind W48 W144 > 18 years, ARV-na ve HIV RNA > 500 c/mL Any CD4 cell count HLA B*5701 negative eGFR 50 mL/min HBs Ag negative No resistance to FTC/3TC, TDF or ABC N = 314 BIC/F/TAF QD DTG/ABC/3TC placebo QD DTG/ABC/3TC QD BIC/F/TAF placebo QD N = 315 * Randomisation was stratified by HIV RNA (< 100 000 c/mL, 100 000-4000 000 c/mL or > 100 000 c/mL), CD4 (< 50/mm3, 50-199/mm3or 200/mm3) at screening and geographic region (USA vs non-USA) BIC/F/TAF: 50/200/25 mg, as STR Objective Non inferiority of BIC/F/TAF at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (lower margin of the 2-sided 95.002% CI for the difference= -12%, 95% power) GS-US-380-1489 Gallant J. Lancet. 2017 Nov 4;390(10107):2063-2072 ; Wohl DA Lancet HIV 2019 ; 6:e355-63
Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Baseline characteristics and patient disposition BIC/F/TAF N = 314 DTG/ABC/3TC N = 315 Median age, years 31 32 Female, % 9 10 HIV RNA (log10 c/mL), median HIV RNA > 100 000 c/mL, % 4.42 4.51 17 16 CD4 cell count (/mm3), median 443 450 CD4 < 200/mm3, % 11 10 Discontinuations at W48 W48-W96 at W48 W48-W96 Total discontinuations, N (%) 19 (6%) 17 (5.8%) 16 (5%) 15 (5%) For lack of efficacy, N 0 0 0 0 For adverse event, N 0 0 4 1 Lost to follow-up, N 9 8 6 6 Non-compliance / Other, N 1 / 9 1 / 8 1 / 5 2 / 6 GS-US-380-1489 Gallant J. Lancet. 2017 Nov 4;390(10107):2063-2072 ; Wohl DA Lancet HIV 2019 ; 6:e355-63
Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Virologic outcome at week 48 % 93.0 100 92.4 BIC/F/TAF DTG/ABC/3TC Difference (95 % CI) 80 DTG/ABC/3TC BIC/F/TAF 60 - 0.6 40 - 4.8 3.6 20 + 12% 12% 0 6.7 4.4 2.5 Met criteria for resistance testing (HIV RNA 200 c/mL) BIC/F/TAF: 1 vsDTG/ABC/3TC: 4 No resistance emergence Mean CD4 increase at W48 BIC/F/TAF: + 233/mm3 DTG/ABC/3TC: + 229/mm3 1.0 0 HIV RNA < 50 c/mL HIV RNA 50 c/mL No data HIV RNA < 50 c/mL (per-protocol) BIC/F/TAF: 99.3% DTG/ABC/3TC: 98.6% GS-US-380-1489 Gallant J. Lancet. 2017 Nov 4;390(10107):2063-2072
Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD HIV RNA < 50 c/mL at W48 according to baseline CD4 and HIV RNA, ITT-E snapshot BIC/F/TAF DTG/ABC/3TC % 94 94 100 94 93 90 87 83 81 80 60 40 20 261 265 53 50 278 283 36 32 N= 0 > 100 000 > 200 100 000 200 HIV RNA, c/ml CD4/mm3 GS-US-380-1489 Gallant J. Lancet. 2017 Nov 4;390(10107):2063-2072
Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Adverse events at W48 BIC/F/TAF N = 314 0 DTG/ABC/3TC N = 315 4 * Adverse events leading to study drug discontinuation, N Adverse event 5% in either group, % Diarrhea Headache Nausea Nasopharyngitis Cough Upper respiratory tract infection Fatigue Syphilis Insomnia Arthralgia Vomiting Bronchitis Abdominal pain Grade 3-4 laboratory abnormalities, % CK elevation LDL-cholesterol elevation Amylase Neutropenia * Nausea, rash ; thrombocytopenia ; chronic pancreatitis, steatorrhea ; depression ** p < 0.001 12.7 11.5 10.2 7.3 6.4 6.4 6.1 3.8 4.5 3.5 3.8 3.2 2.9 13.0 13.7 22.9 ** 9.2 2.5 10.8 8.6 7.9 6.3 6.0 5.4 5.1 5.1 3.5 2.3 1.9 1.6 3.3 2.6 2.2 3.2 GS-US-380-1489 Gallant J. Lancet. 2017 Nov 4;390(10107):2063-2072
Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Renal parameters, bone mineral density and lipid changes at W48 BIC/F/TAF N = 314 DTG/ABC/3TC N = 315 Median change in eGFR (Cockroft-Gault), mL/min - 10.5 - 10.8 Median percent changes in quantitative proteinuria, % Urine albumin: creatinine Retinol binding protein : creatinine Beta2-microglobulin : creatinine 0.6 14 - 23 6 20 - 18 Mean % changes in bone mineral density, % Hip Spine - 0.6 - 0.78 - 0.83 - 1.02 Mean changes in fasting lipids, mg/dL Total cholesterol LDL cholesterol HDL cholesterol Triglycerides None of the differences between groups were significant No discontinuations due to renal adverse events and no proximal tubulopathy in either arm 13 7 5 9 11 4 5 3 GS-US-380-1489 Gallant J. Lancet. 2017 Nov 4;390(10107):2063-2072
Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Steady-state pharmacokinetic parameters of BIC/F/TAF (N = 17) Bictegravir FTC TAF AUCtau (hr*ng/mL) Mean (% CV ; min-max 96 181.5 10 896.4 206.0 (33.5 ; 36 194-154 317) (29.8 ; 5 602.3-20 773.3) (51.2 ; 101.5-458.4) Cmax (ng/mL) Mean (% CV ; min-max) 6 704.7 1 868 225.5 (27.5 ; 3 550-9 550) (34.5 ; 822-3 220) (68.3 ; 73.3-713) Ctau (ng/mL) * Mean (% CV ; min-max) 2 311.7 * 80.9 - (40.7 ; 429-4 030) (37.1 ; 39.5-172.0) Tmax(h) Median (Q1-Q3) 1.53 (1.00-2.07) 1.50 (1.00-1.55) 0.53 (0.50-1.03) t1/2 (h) Median (Q1-Q3) 15.93 (14.50-17.78) 6.66 (6.32-7.17) 0.42 (0.36-0.49) * BIC mean Ctauabout 14 times higher than the protein adjusted effective concentration (162 ng/mL) against wild type HIV-1 virus GS-US-380-1489 Gallant J. Lancet. 2017 Nov 4;390(10107):2063-2072
Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Summary of week 48 results Initial HIV-1 therapy with BIC/F/TAF was non inferior to DTG/ABC/3TC at W48 by snapshot algorithm 92.4% of patients on BIC/F/TAF and 93.0% of patients on DTG/ABC/3TC had HIV-1 RNA < 50 copies/mL Sensitivity analyses confirmed non inferiority No treatment emergent resistance BIC/F/TAF was well tolerated, with no adverse events leading to discontinuation Nausea was reported significantly more frequently in patients treated with DTG/ABC/3TC (p < 0.001) Gastrointestinal, neuropsychiatric, and sleep-related symptoms were reported more frequently in patients treated with DTG/ABC/3TC Changes from baseline in bone mineral density, lipid parameters and renal markers were comparable between treatment arms GS-US-380-1489 Gallant J. Lancet. 2017 Nov 4;390(10107):2063-2072
Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Virologic outcome at week 96, ITT snapshot % 100 89.8 Difference (95 % CI) 87.9 BIC/F/TAF (N = 314) 80 DTG/3TC/ABC BIC/F/TAF DTG/3TC/ABC (N = 315) 60 - 1.9 40 11.5 - 6.9 3.1 7.9 20 0.6 2.2 0 HIV RNA < 50 c/mL HIV RNA 50 c/mL No virologic data -12 % 0 12 % Secondary endpoints at week 96 BIC/F/TAF DTG/3TC/ABC Per protocol 99.6% 98.9% HIV RNA < 50 c/mL (sensitivity analyses) Missing = failure 87.9% 90,8% Missing = excluded 98.9% 99.3% Virologic failure with confirmed HIV RNA > 200 c/mL N assessed for resistance N with emergence of resistance 0 0 5 0 Mean change in CD4 at W96 + 287/mm3 + 288/mm3 GS-US-380-1489 Wohl DA Lancet HIV 2019 ; 6:e355-63
Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Adverse events at W96 Discontinuation for adverse event BIC/F/TAF (N = 314) DTG/3TC/ABC (N = 315) 0 5 (1.6%) Nausea, rash (D4) Thrombocytopenia (D50) Chronic pancreatitis (D134) Depression (D248) Renal failure (D621) Adverse events all grades (%) BIC/F/TAF (N = 314) DTG/3TC/ABC (N = 315) Nausea 11 * 24 * Headache 13 16 Diarrhea 15 16 Fatigue 9 11 Insomnia 7 10 * p < 0.001 GS-US-380-1489 Wohl DA Lancet HIV 2019 ; 6:e355-63
Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Laboratory parameters (W96) BIC/F/TAF (N = 314) DTG/3TC/ABC (N = 315) p CK grade 3-4, % 6 5 - LDL-cholesterol grade 3-4, % 3 4 - Median change in eGFRCG, mL/min - 7.8 - 9.6 0.01 Median % change in urine albumine:creatinine ratio - 0.3 + 5.2 0.25 Median % change in urine retinol binding protein:creatinine ratio + 21.2 + 22.1 0.91 Median % change in urine beta-2- microglobulin:creatinine ratio - 30.8 - 29.4 0.96 Bone DXA: mean % change in BMD between D0 and W96 BIC/F/TAF (N = 314) DTG/3TC/ABC (N = 315) p Spine, % - 0.71 - 0.22 0.14 Hip, % - 1.13 - 1.26 0.59 GS-US-380-1489 Wohl DA Lancet HIV 2019 ; 6:e355-63
Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Mean changes in fasting lipids at W96, mg/dL Total cholesterol: HDL-cholesterol Ratio Total cholesterol LDL- HDL- Triglycerides cholesterol cholesterol p = 0.002 p < 0.001 p = 0.17 p = 0.28 p = 0.003 30 0.5 20 17 15 0 - 0.1 8 8 10 7 -0.2 6 5 -0.5 4 87,9 0 -1 Mean baseline value, mg/dL 159 162 101 101 42 42 93 96 3.7 3.7 BIC/FTC/TAF DTG/ABC/3TC % of patients on lipid-lowering agents at baseline 3.8 % 2.2 % % of patients initiating lipid-lowering agents during study 4.1% 3.8 % GS-US-380-1489 Wohl DA Lancet HIV 2019 ; 6:e355-63
Study GS-US-380-1489: BIC/F/TAF QD vs DTG/ABC/3TC QD Summary of week 96 results Initial HIV-1 therapy with BIC/F/TAF was non inferior to DTG/ABC/3TC at W96 by snapshot algorithm 87.9% of patients on BIC/F/TAF and 89.8% of patients on DTG/ABC/3TC had HIV-1 RNA < 50 copies/mL No treatment emergent resistance BIC/F/TAF was well tolerated, with no adverse events leading to discontinuation Nausea was reported significantly more frequently in patients treated with DTG/ABC/3TC (p < 0.001) Gastrointestinal, neuropsychiatric, and sleep-related symptoms were reported more frequently in patients treated with DTG/ABC/3TC Decrease in eGFR was significantly higher on DTG/ABC/3TC Increase in total-cholesterol and LDL-cholesterol was significantly higher on BIC/F/TAF, but the proportion of participants initiating lipid-lowering agents was not different between arms GS-US-380-1489 Wohl DA Lancet HIV 2019 ; 6:e355-63
