Comparison of INSTI vs EFV
Study GS-US-236-0102: EVG/c/FTC/TDF QD vs EFV/FTC/TDF QD
Original article : Lancet. 2012 Jun 30;379(9835):2439-48 - PE Sax, J Acquir Immune Defic Syndr. 2013 May 1;63(1):96-100 - A Zolopa, J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):e118-20 - DA Wohl
Last update :
09/10/2014
Dr Anton Pozniak
Chelsea and Westminster Hospital
London, UK
- At 48 weeks :
- EVG/c/FTC/TDF QD is virologically non inferior to EFV/FTC/TDF
- Similar virologic reponse of the 2 regimens in different subgroups of patients, including those high HIV RNA at enrolment
- Discontinuation because of adverse events : 4 % vs 5 %
- Development of major resistance mutations occurred in
- 8 patients on EVG/c/FTC/TDF : 7 with integrase mutations, 8 with NRTI mutations
- 8 patients on EFV/FTC/TDF : 8 with NNRTI mutations, 2 with NRTI mutations
- Incidence of adverse events was similar except for neuropsychiatric adverse events and rash (more frequent with EFV/FTC/TDF), and nausea (more frequent with EVG/c/FTC/TDF)
- Median increases in creatinine with decreases in estimated glomerular filtration rate more pronounced with EVG/c/FTC/TDF
- Five patients on EVG/c/FTC/TDF discontinued for renal events
- Week 144 results :
- Durable efficacy of EVG/c/FTC/TDF, with no new renal safety signal and a longer-term safety profile that is differentiated from EFV/FTC/TDF
Design :
*Randomisation was stratified by HIV RNA (< or > 100,000 c/mL) at screening
Objective :
- Non inferiority of EVG/c/FTC/TDF at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (lower margin of the 2-sided 95% CI for the difference= -12%, 95% power)
Baseline characteristics and patient disposition :
Response to treatment at week 48 :
Viral suppression was high in both treatment arms, for various Subgroups including patients with HIV RNA > 100 000 c/mL at baseline
Mean CD4/mm3 increase at W48 :
+ 239 (EVG/c/FTC/TDF) vs
+ 206 (EFV/FTC/TDF), P = 0.009
Response to treatment at week 96 and week 144 :
Secondary efficacy outcomes at week 144 :
Median (IQR) change in creatinine and eGFR at week 48
Virologic failure definition
- Suboptimal virologic response: 2 consecutive visits with HIV RNA ≥ 50 c/mL and < 1 log10 c/mL below baseline at or after week 8,
- Virologic rebound: 2 consecutive visits with HIV RNA either ≥ 400 c/mL after achieving HIV RNA <50 c/mL, or > 1 log10 c/mL increase from nadir,
- HIV RNA ≥ 400 c/mL at their last visit (at or after week 8)
Criteria for resistance testing
- Virological failure or HIV RNA ≥ 400 c/mL at study discontinuation (at or after W8 and taking study drug)
* Q148R, N = 1, N155H, N = 1, E92Q, N = 7, T66I, N = 1 ;
** K103N, N = 7, K101E, N = 3, V108I, N = 1, Y188F/H/K, N = 1, G190A, N = 1
Resistance data at week 144 :
CuTreatment-emergent adverse events leading to premature discontinuation of study drugs :
Adverse events occurring in > 10% of patients in either group (W48) :
Laboratory test results at week 48
Discontinuation for renal event :
- EVG/c/FTC/TDF
- 5 between D0 and W48: 4/5 patients developed signs of tubular toxicity (hypophosphataemia, and/or glycosuria, and/or proteinuria
- 2 between W48 and W96 : decreased GFR, renal failure
- 1 between W96 and W144 : creatinine increase, without tubulopathy
- EFV/FTC/TDF
Discontinuation for neuropsychiatric event :
- EVG/c/FTC/TDF
- EFV/FTC/TDF
- 6 before W48, 4between W48 and W96, none between W96 and W144
Discontinuation for rash :
- EVG/c/FTC/TDF
- EFV/FTC/TDF
- 4 before W48, none between W48 and W144
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