Switch to ATVr 3 TC SALT Study SALT

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Switch to ATV/r + 3 TC § SALT Study

Switch to ATV/r + 3 TC § SALT Study

SALT Study: switch to ATV/r + 3 TC § Design Randomisation* 1: 1 Open-label

SALT Study: switch to ATV/r + 3 TC § Design Randomisation* 1: 1 Open-label ≥ 18 years Stable 3 -drug regimen No previous treatment failure HIV RNA < 50 c/m. L > 6 months Switch for toxicity, intolerance or simplification No resistance to study medications HBs Ag negative N = 143 W 48 W 96 ATV/r 300/100 mg QD + 2 NRTI (investigator-selected) ATV/r 300/100 mg + 3 TC 300 mg QD * Randomisation was stratified on active HCV infection and previous treatment (NNRTI, PI/r, CCR 5 antagonist, integrase inhibitor) § Objective – Primary Endpoint: proportion with treatment success at W 48 • Treatment failure: treatment discontinuation or modification for any cause or confirmed virologic rebound (2 consecutive HIV RNA > 50 c/m. L) • Non-inferiority of ATV/r + 3 TC (per protocol) ; lower limit of the 95% CI for the difference = -12% SALT Perez-Molina JA. Lancet Infect Dis 2015; 15: 775 -84

SALT Study: switch to ATV/r + 3 TC Baseline characteristics and disposition at W

SALT Study: switch to ATV/r + 3 TC Baseline characteristics and disposition at W 48 ATV/r + 2 NRTI N = 143 ATV/r + 3 TC N = 143 Female 22% 31% Baseline CD 4/mm 3, median 614 579 Nadir CD 4/mm 3, median 215 211 Duration of HIV RNA < 50 c/m. L (months), median 29 27 Duration of ART prior to study entry, median 41 39 HCV co-infection (RNA positive) 20% Reason for switching Simplification Toxicity Intolerance 80% 14% 4% 74% 22% 3% Switched treatment NNRTI PI/r 32% 66% 33% 64% 29 (20%) 21 (15%) Adverse event / confirmed virologic failure 10 / 4 3/5 Withdrew consent / lost to follow-up 9/4 7/4 Discontinued at W 48, N (%) SALT Perez-Molina JA. Lancet Infect Dis 2015; 15: 775 -84

SALT Study: switch to ATV/r + 3 TC Efficacy and Safety Results (W 48)

SALT Study: switch to ATV/r + 3 TC Efficacy and Safety Results (W 48) HIV RNA < 50 c/m. L at W 48 (Per protocol, TLOVR) ATV/r + 2 INTI 100 80 ATV/r + 3 TC % ATV/r + 3 TC 4 5 1 (M 184 V) 0 N 78 20 105/ 135 Safety, N (%) 83 40 SALT ATV/r + 2 NRTI Emergence of resistance mutations 60 0 Confirmed virologic rebound 111/ 113 ≠ (95%CI) 6 (- 5 ; 16) ATV/r + 2 NRTI N = 141 ATV/r + 3 TC N = 140 AEs leading to discontinuation 10 (7. 2%) 3 (2. 2%) Grade 3 -4 AEs Hyperbilirubinemia Icterus Liver function test Hyperlipidemia Thrombocytopenia 78 (55%) 71 2 2 2 1 77 (55%) 72 0 2 3 2 8 6 Severe adverse events (none related to study medication) Perez-Molina JA. Lancet Infect Dis 2015; 15: 775 -84

SALT Study: switch to ATV/r + 3 TC Efficacy and Safety Results (W 96)

SALT Study: switch to ATV/r + 3 TC Efficacy and Safety Results (W 96) HIV RNA < 50 c/m. L at W 96 (Per protocol, TLOVR) ATV/r + 2 INTI ATV/r + 3 TC Confirmed virologic rebound N Samples amplified Emergence of resistance mutations 100 % 80 73. 9 0 99/ 134 99/ 133 ≠ (95%CI) 0. 5 (- 9. 9 ; 11) SALT 5 9 2/5 3/9 1 (M 184 V) 0 ATV/r + 2 NRTI N = 141 ATV/r + 3 TC N = 140 AEs leading to discontinuation 10 (7. 1%) 7 (5. 0%) Grade 3 -4 AEs Hyperbilirubinemia Jaundice Liver function test Hyperlipidemia Thrombocytopenia 99 (70%) 66 1. 4 0. 7 2. 1 0. 7 99 (71%) 65 0 2. 1 1. 4 - 6. 2% - 1. 9% + 12. 1% (p < 0. 003) + 5. 1% (p < 0. 001) 60 20 ATV/r + 3 TC Safety, N (%) 74. 4 40 ATV/r + 2 NRTI Changes at W 96 in triglycerides Changes at W 96 in total cholesterol Perez-Molina JA, JAC 2017; 72: 246 -53

SALT Study: switch to ATV/r + 3 TC § Conclusion – Switching to ATV/r

SALT Study: switch to ATV/r + 3 TC § Conclusion – Switching to ATV/r + 3 TC is effective, safe, and non-inferior to ATV/r + 2 NRTI in virologically suppressed HIV+ patients, who need change any antiretroviral previous triple therapy because of toxicity, intolerance or simplification • Switching from a triple to a dual ATV-based regimen is not associated with an increased risk of virological failure, which was low in both groups, with most patients with virological failure with HIV RNA < 200 c/ml • Frequency of blips throughout the 48 weeks was equivalent in both groups • Only 1 patient (triple-treatment group) developed resistance mutation (M 184 V) • Few patients discontinued the study in the 2 groups because of toxic effects, with treatment interruptions being significantly more frequent in the triple-treatment group • No significant differences in change from baseline in neurocognitive function, neither renal function, bone mineral density, or fat gain or distribution between groups at week 96 SALT Perez-Molina JA. Lancet Infect Dis 2015; 15: 775 -84, Perez-Molina JA, JAC 2017; 72: 246 -53