1 / 10

Comparison of INSTI vs EFV

Comparison of INSTI vs EFV. STARTMRK GS-US-236-0102 SINGLE. SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD. Design. Randomisation* 1 : 1 Double-blind. W96. W144. > 18 years ARV-naïve HIV RNA > 1,000 c/mL Any CD4 cell count HBsAg negative No genotypic resistance

xander-hebert
Download Presentation

Comparison of INSTI vs EFV

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. Comparison of INSTI vs EFV • STARTMRK • GS-US-236-0102 • SINGLE

  2. SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD • Design Randomisation* 1 : 1 Double-blind W96 W144 > 18 years ARV-naïve HIV RNA > 1,000 c/mL Any CD4 cell count HBsAg negative No genotypic resistance HLA-B*5701 negative N = 422 Open-label N = 422 *Randomisation was stratified by HIV RNA (< or > 100,000 c/mL) and CD4/mm3 (< or > 200) at screening • Objective • Non inferiority of DTG at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (1-sided significance level of 2.5%, lower margin of the 95% CI for the difference = -10%, 90% power) Walmsley S. NEJM 2013;369:1807-18 SINGLE

  3. SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD Baseline characteristics and patient disposition Walmsley S. NEJM 2013;369:1807-18 SINGLE

  4. SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD Response to treatment at week 48 HIV RNA < 50 c/mL Primaryanalysis DTG + ABC/3TC % TDF/FTC/EFV 100 87.9 89.8 81.3 80.7 Differences in viral suppression were also seen in key demographic subgroups including race, sex, age and patients with HIV RNA > 100,000 c/mL at baseline 75 50 25 Adjusted mean CD4/mm3 increase at W48 : + 267 for DTG + ABC/3TC + 208 for TDF/FTC/EFV (p<0.001) 0 ITT, snapshot Per protocol Adjusted difference (95% CI)= 7% (2; 12) Adjusted difference (95% CI)= 9% (4; 13)  Superiority of DTG + ABC/3TC Walmsley S. NEJM 2013;369:1807-18 SINGLE

  5. SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD HIV-1 RNA < 50 c/mL at week 48 by stratification factors Walmsley S. NEJM 2013;369:1807-18 SINGLE

  6. SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD Response to treatment at week 96 HIV-1 RNA < 50 c/ml (ITT, snapshot) DTG + ABC/3TC TDF/FTC/EFV % 100 DTG : 80% 80 EFV : 72% 60 Adjusted difference at W96 (95 % CI) :+ 8.0 % (+ 2.3 % ; + 13.8 %) ; P = 0.006 40 20 0 0 4 8 12 16 24 32 40 48 60 72 84 96 Weeks Walmsley S, CROI 2014, Abs. 543 SINGLE

  7. SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD • Virologic failure definition • 2 consecutive plasma HIV-1 RNA > 50 c/mL, on or after W24 • Criteria for resistance testing • All patients with protocol defined virologic failure (PDVF) • Genotype of RT and integrase on baseline and suspected virologic failure samples Resistance data at PDVF * E157Q/P polymorphism in 1 patient with no change in phenotype ** N = 1 with K101E, N = 1 with K103N, N = 1 with G190A, N = 1 with K103N + G190A ; **** N = 2 with K103K/N SINGLE Walmsley S, ICAAC 2012, Abs.H556b ; Walmsley S. NEJM 2013;369:807-18 ; Walmsley S, CROI 2014, Abs.543

  8. SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD Adverse events and laboratory abnormalities at week 48 Walmsley S. NEJM 2013;369:1807-18 SINGLE

  9. SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD • Insomnia was more frequent in DTG group (15% vs 10%) • Serious adverse events related to study drug at week 48 • DTG + ABC/3TC, N = 1 • Suspected drug hypersensitivity • TDF/FTC/EFV, N = 8 • Psychiatric event, N = 4 • Drug hypersensitivity, N = 2 • Cerebrovascular accident, N = 1 • Renal failure, N = 1 • Mean change in creatinine at W48 on DTG: + 0.12 to 0.15 mg/dL (10.56 to 13.2 mmol/L), peak at W2, then stable Walmsley S. NEJM 2013;369:1807-18 SINGLE

  10. Conclusion DTG + ABC/3TC QD had a better safety profile and was superior through 48 weeks to TDF/FTC/EFV for first-line antiretroviral therapy Superior virologic response with DTG + ABC/3TC also seen in key demographic subgroups and in patients with low or high baseline viral load Statistical superiority in CD4 response for DTG + ABC/3TC Virologic superiority of DTG + ABC/3TC confirmed at W96 No INSTI major mutations were detected through 96 weeks with DTG Lower occurrence of adverse events leading to discontinuation with DTG : 2% vs 10% Significant lower reported rates of neuro-psychiatric and rash events with DTG + ABC/3TC Except for insomnia (15% vs 10%) SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD SINGLE Walmsley S. NEJM 2013;369:807-18 ; Walmsley S, CROI 2014, Abs.543

More Related