Switch to ATV/r + 3TC  SALT Study

ATV/r 300/100 mg qd + 2 NRTI (investigator-selected) N = 143 ATV/r 300/100 mg + 3TC 300 mg qd  Design Randomisation* 1: 1 Open-label  Objective –Primary Endpoint : proportion with treatment success at W48 Treatment failure : treatment discontinuation or modification for any cause or confirmed virologic rebound (2 consecutive HIV RNA > 50 c/mL) Non-inferiority of ATV/r + 3TC (per protocol) ; lower limit of the 95% CI for the difference = -12% Perez-Molina JA. Lancet Infect Dis 2015;15: ≥ 18 years Stable 3-drug regimen No previous treatment failure HIV RNA 6 months Switch for toxicity, intolerance or simplification No resistance to study medications HBs Ag negative W48W96 SALT Study: switch to ATV/r + 3TC SALT * Randomisation was stratified on active HCV infection and previous treatment (NNRTI, PI/r, CCR5 antagonist, integrase inhibitor)

Baseline characteristics and disposition ATV/r + 2 NRTI N = 143 ATV/r + 3TC N = 143 Female22%31% Baseline CD4/mm 3, median Nadir CD4/mm 3, median Duration of HIV RNA < 50 c/mL (months), median2927 Duration of ART prior to study entry, median4139 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% Discontinued at W48, N (%)29 (20%)21 (15%) Adverse event / confirmed virologic failure10 / 43 / 5 Withdrew consent / lost to follow-up9 / 47 / 4 SALT Study: switch to ATV/r + 3TC SALT Perez-Molina JA. Lancet Infect Dis 2015;15:775-84

HIV RNA < 50 c/mL at W48 (Per protocol, TLOVR) ATV/r + 3TCATV/r + 2 NRTI Confirmed virologic rebound Efficacy and Safety results ATV/r + 2 NRTIATV/r + 3TC N45 Emergence of resistance mutations 1 (M184V)0 ATV/r + 2 NRTI N = 141 ATV/r + 3TC N = 140 AEs leading to discontinuation10 (7.2%)3 (2.2%) Grade 3-4 AEs Hyperbilirubinemia Icterus Liver function test Hyperlipidemia Thrombocytopenia 78 (55%) (55%) Severe adverse events (none related to study medication) 86 Safety, N (%) SALT Study: switch to ATV/r + 3TC SALT Perez-Molina JA. Lancet Infect Dis 2015;15: ≠ (95%CI) 6 (- 5 ; 16) % 111/ / 135

 Conclusion – Switching to ATV/r + 3TC 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 (M184V) 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, renal function, bone mineral density, or fat gain or distribution between groups at week 48 SALT SALT Study: switch to ATV/r + 3TC Perez-Molina JA. Lancet Infect Dis 2015;15:775-84