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Comparison of INSTI vs PI
Study GS-236-0103: EVG/c/FTC/TDF QD vs
ATV/r + FTC/TDF QD
Original article : Lancet. 2012 Jun 30;379(9835):2429-38 - E DeJesus, J Acquir Immune Defic Syndr. 2013 Apr 15;62(5):483-6 - JK Rockstroh, J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):e121-4 - N Clumeck
Last update : 09/10/2014

Dr Anton Pozniak
Chelsea and Westminster Hospital
London, UK

• 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 intentionto 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 patientswith HIV RNA > 100 000 c/mLat 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/mLand <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

 

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