Head-to-head comparative trials for first line ART since 2006

Comparison of INSTI vs EFV
SINGLE Study: DTG + ABC/3TC vs TDF/FTC/EFV QD
Original article : N Engl J Med. 2013 Nov 7;369(19):1807-18 - SL Walmsley, JAIDS 2015; 70:515-9 - SL Walmsley, ICAAC 2012. Abs.H556b - SL Walmsley, ICAAC 2014, Abs. H-647a - Pappa K & AIDS 2015; 29:2459-64 - Tebas P
Last update : 01/12/2015

Dr Anton Pozniak
Chelsea and Westminster Hospital
London, UK

  • 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 and W144
  • No INSTI major mutations were detected through 144 weeks with DTG
  • Lower occurrence of adverse events leading to discontinuation with DTG : 2% vs 10% at W48 ; 4% vs 14% at W144
  • Significant lower reported rates of neuro-psychiatric and rash events with DTG + ABC/3TC
    • Except for insomnia (15% vs 10% at W48)

Design :


*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)

Baseline characteristics and patient disposition :

Response to treatment at week 48 :








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

Adjusted mean CD4/mm3 increase at W48 :
+ 267 for DTG + ABC/3TC
+ 208 for TDF/FTC/EFV (p<0.001)

Response to treatment at week 96 :

HIV-1 RNA < 50 c/mL at W144, ITT snapshot

HIV-1 RNA < 50 c/mL by baseline stratification factors

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

Adverse events and laboratory abnormalities at week 48 :

Insomnia was more frequent in DTG group at W48 (15% vs 10%)

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

Serious adverse events related to study drug at week 48

« ABC HSR » was reported between W0 and W96 in 2 patients in the DTG + ABC/3TC arm vs 5 in the TDF/FTC/EFV arm

Mean change from baseline in bone turnover markers (%)

 

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