Switch to EVG/c/FTC/TDF  STRATEGY-PI Study  STRATEGY-NNRTI Study

 Design  Endpoints –Primary: proportion of patients maintaining HIV RNA 0, assessment for superiority –Secondary: proportion of patients maintaining HIV RNA < 50 c/mL at W48 (TLOVR algorithm), CD4, safety, tolerability to W96 Switch to EVG/c/FTC/TDF Continue NNRTI + FTC + TDF Pozniak A. Lancet Infect Dis 2014;14:590-9 STRATEGY-NNRTI Randomisation* 2 : 1 Open-label HIV+ ≥ 18 years On FTC + TDF + NNRTI HIV RNA 6 months No virologic failure Genotype testing before ART with no resistance to study drugs Integrase inhibitor naïve eGFR > 70 mL/mim N = 147 N = 292 W48W96 * Randomisation stratified by EFV use at screening STRATEGY-NNRTI Study: Switch NNRTI to EVG/c

EVG/c/FTC/TDF N = 291 NNRTI + FTC + TDF N = 143 Median age, years4339 Female8%6% Time since HIV diagnosis, median years55 On first ARV regimen90%91% NNRTI at randomisation Efavirenz (coformulated EFV/FTC/TDF)80% (76%)74% (70%) Nevirapine16%19% Rilpivirine3%7% Etravirine1%0 CD4 cell count (/mm 3 ), median Hepatitis B / hepatitis C coinfection2% / 4%2% / 1% Discontinuation by W Pozniak A. Lancet Infect Dis 2014;14:590-9 STRATEGY-NNRTI Baseline characteristics and patient disposition

Virologic outcome at W48 (mITT, snapshot) Difference (95% CI) = 5.3% (-0.5 to 12.0) 1 1 N = 3N = Pozniak A. Lancet Infect Dis 2014;14:590-9 STRATEGY-NNRTI EVG/c/FTC/TDF NNRTI + FTC + TDF % HIV RNA < 50 c/mL HIV RNA ≥ 50 c/mL No virologic data STRATEGY-NNRTI Study: Switch NNRTI to EVG/c

Pozniak A. Lancet Infect Dis 2014;14:590-9 STRATEGY-NNRTI HIV RNA < 50 c/mL Sensitivity and secondary analysis EGV/c/FTC/TDFNNRTI + FTC + TDF Per-proctol99% Difference: 0.1% (95% CI: to 3.5) ITT-TLOVR92%87% Difference: 5.0% (95% CI: -1.1 to 12.1)  One participant in each group met the criteria for resistance testing (HIV RNA > 400 c/mL at virologic failure or early discontinuation) –No emergence of resistance –Both remained on study treatment and achieved HIV RNA < 50 c/mL after W48 STRATEGY-NNRTI Study: Switch NNRTI to EVG/c

Virologic sucess overall and by subgroup at W48 (mITT) Pozniak A. Lancet Infect Dis 2014;14:590-9 STRATEGY-NNRTI Overall Age < 40 years Age > 40 years Male Female White Non-white Efavirenz Non-efavirenz On first regimen at baseline On second regimen at baseline Virological success (%) 271/ / /114 62/74 164/176 64/69 251/ /134 20/23 7/9 216/230 99/109 55/60 27/34 214/231 91/106 57/59 35/37 245/ /130 25/27 11/12 n/N Favours not switching Switch group No-switch group Difference (%) Favours switching STRATEGY-NNRTI Study: Switch NNRTI to EVG/c

Adverse events and grade 3-4 laboratory abnormalities * neuromuscular symptoms, suicide, dysgueusia, prurigo, Fanconi syndrome, increased creatinine ** altered mood Pozniak A. Lancet Infect Dis 2014;14:590-9 STRATEGY-NNRTI STRATEGY-NNRTI Study: Switch NNRTI to EVG/c EVG/c/FTC/TDFNNRTI + FTC + TDF Any adverse event, 81%75% Grade 3 or 4 AE 7%6% Serious adverse event 5%4% Discontinuation because of AE N = 6 (2%)*N = 1 (1%)** Death N = 10 AE occurring more frequently in one group14%23% Headache (p = 0.03) 3%1% Nausea (p = 0.05) 2%6% Cough (p= 0.04) 2%1% Fatigue (p = 0.02) 2%1%

STRATEGY-NNRTI Study: Switch NNRTI to EVG/c  Other safety data –Incidence and prevalence of headache and nausea became similar between groups by week 12 –Grade 3-4 laboratory abnormalities : 10% in the switch group vs 14% in the no-switch group –Creatinine increase in switch group at week 4, stabilizing up to week 48 (median +11  mol/L) –Small decrease in HDL-cholesterol in the switch group vs no change in the no-switch group –In the subgroup switched form EFV + FTC + TDF to EVG/c/FTC/TDF Improvement in lipids HIV Symptom Index : improvement of CNS symptoms Higher treatment satisfaction score at W4 and W24 Pozniak A. Lancet Infect Dis 2014;14:590-9 STRATEGY-NNRTI

STRATEGY-NNRTI Study: Switch NNRTI to EVG/c  Conclusion –Coformulated EVG/c/FTC/TDF is non-inferior to continuing an existing regimen of NNRTI plus FTC and TDF in virologically suppressed, HIV- infected adults with no history of virological failure or resistance to FTC or TDF. –Low frequency of virologic failure and absence of emergent resistance in the group switched to EVG/c/FTC/TDF –Rare discontinuations because of adverse events –Fatigue, cough, headache and nausea were more frequent in the switch group ; –Rates of CNS symptoms decreased in patients switched from EFV –Increase in creatinine similar to that of phase 3 of EGV/c/FTC/TDF –Moderate improvement in lipids in patients switched from EFV –EVG/c/FTC/TDF is a switch option in virologically suppressed patients with no history of virological failure on an NNRTI regimen, when its continuation is not suitable Pozniak A. Lancet Infect Dis 2014;14:590-9 STRATEGY-NNRTI