DeJesus E. Lancet. 2012 Jun 30;379(9835):2429-38. ; Rockstroh JK. J Acquir Immune Defic Syndr. 2013 Apr 15;62(5):483-6. ; Clumeck N. J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):e121-4
Head-to-head comparative trials for first line ART since 2006
» INSTI vs PI
» EVG/C/FTC/TDF vs ATV/r + FTC/TDF
E/C/F/TDF, EVG/c, ATV/r, FTC/TDF, TDF, FTC
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- At 48 weeks of treatment :
- EVG/c/FTC/TDFQD was virologically non inferior to ATV/r + FTC/TDF
- Similar virologic reponse of the 2 regimens in different subgroups of patients, including those with high HIV RNA at enrolment
- Discontinuation because of adverse events was lower with EVG/c/FTC/TDF : 3.7% vs 5.1%
- Development of major resistance mutations occurred in
- 5 patients on EVG/c/FTC/TDF : 4 with integrase mutations (3/4 had also NRTI mutations), 1 with only RT mutation (M184V)
- none on ATV/r + FTC/TDF
- Incidence of adverse events was similar except for jaundice/icterus
- Median increases in creatinine with accompanying decreases in estimated glomerular filtration rate
- occurred in both study groups by week 2
- generally stabilized by week 8 and did not change up to week 48
- median change : + 11 μmol/L vs + 7 μmol/L ; P < 0.001
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 :
+ 207 (EVG/c/FTC/TDF) vs
+ 211 (ATV/r + FTC/TDF)
ARN VIH < 50 c/ml :
Response to treatment at week 96 and week 144 :
Response to treatment at week 144 :
No treatment difference in virologic success for various subgroups, including patients with HIV RNA > 100,000 c/mL at baseline, except for adherence ≥ 95 % (favoring EVG/c/FTC/TDF)
* p = 0.018
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 = 2, N155H, N = 1, T66I + E92Q + N155H, N = 1 ; ** 1 had also M184V + K65R and 2 M184V
Resistance data at week 144
* INSTI + NRTI resistance, N = 3, ** INSTI + NRTI resistance, N = 1
Treatment-emergent adverse events leading to premature discontinuation of study drugs
Treatment-emergent adverse events occurring in > 10% of patients in either group (week 48)
Laboratory test results at week 48
Median change in serum creatinine (mmol/L) concentration from baseline
Discontinuations due to renal event
