1 / 16

DTG + 3TC vs DTG + TDF/FTC

DTG + 3TC vs DTG + TDF/FTC. GEMINI. GEMINI 1 & 2 Studies : DTG + 3TC vs DTG + TDF/FTC in first-line. Design. Randomisation * 1 : 1 Double-blind. W96. N = 716. HIV+ ≥ 18 years ARV-naïve HIV RNA 1 000-500 000 c/mL No HBV co-infection No major HIV resistance mutations. N = 717.

buckner
Download Presentation

DTG + 3TC vs DTG + TDF/FTC

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. DTG + 3TC vs DTG + TDF/FTC • GEMINI

  2. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line • Design Randomisation * 1 : 1 Double-blind W96 N = 716 HIV+ ≥ 18 years ARV-naïve HIV RNA 1 000-500 000 c/mL No HBV co-infection No major HIV resistance mutations N = 717 * Randomisation stratified by HIV RNA (≤ or > 100 000 c/mL) and CD4 (≤ or > 200/mm3) • Primary endpoint • 2 parallel studies (GEMINI-1 and GEMINI-2), each with a combined number of 710-720 patients and similar endpoint • Proportion of patients with HIV RNA < 50 c/mL at W48, ITT-E analysis, snapshot algorithm ; non-inferiority if lower margin of a one-sided 97.5% CI for the difference = - 10%, 90% power GEMINI Cahn P. Lancet. 2019; 393(10167):143-155

  3. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line Baseline characteristics GEMINI Cahn P. Lancet. 2019; 393(10167):143-155

  4. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line 74 HIV RNA < 50 c/mL by visit, ITT-E snapshot DTG + 3TC (N = 716) DTG + TDF/FTC (N = 717) % 93.3 93 100 91 91 89 90 89,5 88 89 87 93 91.5 89 90 72 80 89 88 86 86 87 85 70 60 Adjusteddifference : - 0.7% (95% CI: - 4.3 to 2.9) Adjusteddifference : - 3.4% (95% CI: - 6.7 to 0.0007) 40 20 0 0 8 16 24 32 40 48 56 64 72 80 88 96 Week • Mean adjusted increase in CD4 between baseline and W48 • DTG + 3TC: + 224/mm3 • DTG + TDF/FTC: + 218/mm3 GEMINI Cahn P. Lancet. 2019; 393(10167):143-155; Cahn P, IAS 2019, Abs. WEAB0404LB

  5. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line 75 HIV RNA < 50 c/mL at W48, GEMINI 1 & 2 pooled Adjusted difference (95% CI) DTG + 3TC DTG + TDF/FTC % ITT-exposed, snapshot 100 91 93 93 94 - 2.6 GEMINI-1ITT-E ** DTG + 3TC - 6.7 1.5 DTG + TDF/FTC 80 - 0.7 GEMINI-2ITT-E ** Per protocol - 4.3 2.9 DTG + 3TC 60 - 1.7 DTG + TDF/FTC GEMINI-1 & 2ITT-E * - 4.4 1.1 40 Per Protocol *** -1.3 1.2 -3.9 20 -10 -8 -6 -4 -2 0 2 4 6 8 10 6 5 5 4 3 2 2 1 716 717 694 693 N= * Adjusted on HIV RNA, CD4, study (GEMINI 1 or 2) ** Adjusted on HIV RNA and CD4** ITT-E population except patients with protocol violation 0 Virologic success Virologic Non-response No virologic data • Conclusion: non inferiority of DTG + 3TC GEMINI Cahn P. Lancet. 2019; 393(10167):143-155

  6. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line ITT-E snapshot analysis, % GEMINI Cahn P. Lancet. 2019; 393(10167):143-155 ; Cahn P, IAS 2019, Abs. WEAB0404LB

  7. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line 76 HIV RNA < 50 c/mL at W96 according to baseline CD4 and HIV RNA, ITT-E snapshot ITT-exposed, snapshot Treatment-related discontinuation = failure DTG + 3TC DTG + TDF/FTC DTG + 3TC DTG + TDF/FTC % 96 96 95 97 94 97 97 94 100 90 90 88 87 87 86 84 80 68 60 40 20 576 564 576 564 140 153 140 153 653 662 653 662 63 55 63 55 N= 0 ≤ 100 000 > 100 000 > 200 ≤ 200 * HIV RNA, c/mL CD4/mm3 * Reasons for snapshot non-response at W96 in participants with baseline CD4 < 200/mm3 • DTG + 3TC (N = 20): 2 with HIV RNA > 50 c/mL, 3 confirmed virologic withdrawal, 1 discontinuation for treatment-related AE, 2 discontinuations for non-treatment-related AE, 3 protocol violations, 3 lost to follow-up, 4 withdrew consent, 1 withdrew to start HCV treatment, 1 change in ART due to incarceration • DTG + TDF/FTC (N = 7): 1 confirmed virologic withdrawal, 3 lost to follow-up, 2 withdrew consent, 1 investigator discretion (incarcerated) GEMINI Cahn P. Lancet. 2019; 393:143-55 ; Cahn P, IAS 2019, Abs. WEAB0404LB ; Van Wyk J. IDWeek 2019, Abs. 2842

  8. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line HIV RNA < 50 c/mL at W48 (%) in subgroups of the pooled analysis Difference, % (95%CI) DTG + 3TC DTG + TDF/FTC DTG + TDF/FTC DTG + 3TC 717 n 1.9 92 140 > 100 000 90 153 • Baseline HIV-1 RNA,copies/ml -2.8 91 576 • ≤ 100 000 94 564 93 653 • > 200 93 49 662 • Baseline CD4+ count,cells/mm3 -0.7 79 63 • ≤ 200 93 668 55 -13.4 89 65 ≥ 50 -0.8 90 80 91 231 Age 35 to < 50 -3.0 94 229 92 420 < 35 93 408 -1.5 88 113 Female -2.3 91 98 Sex -1.7 92 603 Male 94 619 -0.4 • 84 • 99 African heritage 84 76 -0.1 94 71 Asian 94 72 Race -1.6 93 480 White 95 497 -3.8 88 66 Other 92 72 -30 -20 -10 0 10 20 30 0 20 40 60 80 100 GEMINI Orkin C (Abs. P021). JIAS 2018; 21 , suppl. 8:31

  9. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line Time to viral suppression, HIV RNA < 50 c/ml (cumulative incidence): pooled ITT-E population All participants Participants with baseline HIV-1 RNA > 100 000 c/mL DTG + 3TC (N = 716) DTG + 3TC (N = 140) DTG + TDF/FTC (N = 717) DTG + TDF/FTC (N = 153) 1,0 1,0 0,8 0,8 0,6 0,6 0,4 0,4 0,2 0,2 0 0 0 4 8 12 16 24 36 48 60 0 4 8 12 16 24 36 48 60 Weeks Weeks • Median time to viral suppression: DTG + 3TC vs DTG + TDF/FTC = 29.0 vs 29.0 days • Median time to viral suppression: DTG + 3TC vs DTG + TDF/FTC = 57.0 vs 57.0 days GEMINI Eron J. HIV DART and EmergingViruses 2018; Miami, FL. Oral Presentation #7.

  10. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line 96 Virologic outcome at W48 and W96 (ITT snapshot) in patients with baseline HIV RNA > 500 000 c/mL * CD4 < 200/mm3 in 3/13 and 5/15 ** Discontinuation for other reason *** Discontinuation for selection criteria violation (screening HIV RNA > 500 000 c/mL GEMINI Eron J. HIV DART and EmergingViruses 2018; Miami, FL. Oral Presentation #7; Van Wyk J. IDWeek 2019, Abs. 2842

  11. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line Time to HIV RNA < 40 c/mL with target not detected (Kaplan-Meier ) Baseline HIV RNA < 100 000 c/mL All participants 80 % 1.0 79 % 0.8 DTG + 3TC (N = 716) DTG + TDF/FTC (N = 717) 0.6 77 % 0.4 (N = 576) 1.0 (N = 564) 0.2 73 % 0.8 0 0 4 8 12 16 24 36 48 60 72 Weeks 0.6 Baseline HIV RNA > 100 000 c/mL 1.0 0.4 64 % 0.8 52 % 0.2 0.6 0 0.4 (N = 140) 0 4 8 12 16 24 36 48 60 72 (N = 153) 0.2 Weeks 0 0 4 8 12 16 24 36 48 60 72 Weeks GEMINI Underwood M, CROI 2019, Abs. 490

  12. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line • Confirmed virologic withdrawal (CVW) • Decrease from baseline in HIV RNA < 1 log10 c/mL, unless HIV RNA < 200 c/mL, by W12 • Confirmed HIV RNA ≥ 200 c/mL at or after W24 • Confirmed rebound (HIV RNA ≥ 200 c/mL) after confirmed HIV RNA < 200 c/mL • Genotypic and phenotypic resistance tests on initial suspected plasma sample • CVW up to W96 • All were virologic rebounds GEMINI Cahn P. Lancet. 2019; 393(10167):143-155 ; Cahn P, IAS 2019, Abs. WEAB0404LB

  13. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line Adverse events at W48, % GEMINI Cahn P. Lancet. 2019; 393(10167):143-155

  14. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line 78 • Renal markers: adjusted mean change at W48 • Bone turnover biomarkers: adjusted mean change at W48 • Significant higher increase of the biomarkers in DTG + TDF/FTC arm (specific alkaline phosphatase, osteocalcin, procollagen 1-N terminal propeptide and type 1 collagen C-telopeptide) Serum Urine % DTG + 3TC (N = 716) 40 15 13.5 DTG + TDF/FTC (N = 717) 10.4 31.2 10 30 6.3 4.1 5 20 0 11.4 10 -5 2.9 0 -10 -12.1 -10 -7.4 -7.7 -15 -15.5 -13.1 -20 -20 Creatinine (µmol/L) GFR from creatinine, CKD-EPI (mL/min/1,73 m2) GFR from cystatin C, CKD-EPI (mL/min/1,73 m2) Protein/creatinine(g/moL) Retinol-bindingprotein/creatinine(µg/mmoL) Beta-2microglobulin/creatinine(mg/mmoL) p < 0.001 for all comparisons DTG + 3TC vs DTG + TDF/FTC GEMINI Cahn P. Lancet. 2019; 393(10167):143-155

  15. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line Adjusted mean change in fasting lipids at week 48, mmol/L (ITT-E) DTG + 3TC (N = 716) ** DTG + TDF/FTC (N = 717) 5 ↑0.32 ↓0.15 4 ** 3 ↑0.17 ↓0.14 * p < 0.05 ** p < 0.001 * 2 ** ↓0.08 ↑0.03 ↑0.15 ↑0.02 * 1 ↑0.12 ↓0.24 0 Totalcholesterol HDLcholesterol LDLcholesterol Triglycerides Total cholesterol/HDL cholesterol ratio • Baseline values are represented by the main legend colors, changes at W48 by lighter colors GEMINI Cahn P. Lancet. 2019; 393(10167):143-155

  16. GEMINI 1 & 2 Studies: DTG + 3TC vs DTG + TDF/FTC in first-line • Conclusion • The 2DR of dolutegravir plus lamivudine provides high antiviral potency with a high barrier to resistance and favorable safety and tolerability profiles • Non-inferior efficacy and similar tolerability was demonstrated at 48 weeks • Non-inferior efficacy was maintained over 96 weeks • Low rates of confirmed virologic withdrawal through week 96, and no resistance development in either arm • Overall safety and tolerability were comparable between groups • Lower risk of drug-related AEs with DTG + 3TC • Change in renal and bone biomarkers significantly favors DTG + 3TC • Improvements in TC:HDL ratio in both arms GEMINI Cahn P. Lancet. 2019; 393(10167):143-155 ; Cahn P, IAS 2019, Abs. WEAB0404LB

More Related