Switch to ATV/r + RAL  HARNESS Study

ATV/r 300/100 mg qd + TDF/FTC N = 37 N = 72 ATV/r 300/100 mg qd + RAL 400 mg bid  Design Randomisation 2: 1 Open-label  Objective –Primary Endpoint : proportion with treatment success at W24 No power calculation Descriptive analysis HARNESS Van Lunzen J. IAC 2014, Melbourne, Abs. LBPE19 Adults Stable 2 NRTI + 3 rd drug regimen No previous treatment failure HIV RNA 3 months Switch for safety and/or tolerability issues No resistance to study medications HBs Ag negative W24W48 HARNESS Study: switch to ATV/r + RAL

Baseline characteristics and disposition ATV/r + TDF/FTC N = 37 ATV/r + RAL N = 72 Female17%19% Baseline CD4/mm 3, mean Discontinuation at W24, N Adverse event Discontinuation W24-W48, N Adverse event  Criteria for treatment discontinuation – Virologic rebound 2 consecutive HIV RNA > 40 c/mL before or at W24 Last on-treatment HIV RNA > 40 c/mL followed by discontinuation – Discontinuation 2 consecutive HIV RNA > 1000 c/mL ≥ 2 weeks apart and without underlying cause HARNESS HARNESS Study: switch to ATV/r + RAL Van Lunzen J. IAC 2014, Melbourne, Abs. LBPE19

HIV RNA < 40 c/mL (ITT) ATV/r + RALATV/r + TDF/FTC Confirmed virologic rebound, N Efficacy and Safety results ATV/r + TDF/FTCATV/r + RAL N29 Tested isolates05 PI resistance 1* L10V, G16Q, L33F, P39Q, M46L, G48V, Q58E, I62V, L63I/T, I64L, A71V, I72V, V77I, V82A, T91S, I93L INI resistance 2* F21Y Y143C + N155H * 1 patient with both PI and INSTI mutations HARNESS HARNESS Study: switch to ATV/r + RAL Van Lunzen J. IAC 2014, Melbourne, Abs. LBPE % W24 (primary endpoint) W

ATV/r + TDF/FTC N = 37 ATV/r + RAL N = 72 Grade 3-4 AEs513 Grade 2 drug-related AEs Grade 3-4 total bilirubin Renal toxicity61 Safety at W48, N HARNESS Van Lunzen J. IAC 2014, Melbourne, Abs. LBPE19 HARNESS Study: switch to ATV/r + RAL

 Conclusion – In virologically suppressed patients on a triple-drug antiretroviral regimen, switching to ATV/r + RAL was well tolerated but resulted in a higher incidence of virologic rebound than in the ATV/r + TDF/FTC group at Week 24 and Week 48 – IDMC recommended stopping the trial because of virologic rebound and resistance in the ATV/r + RAL arm HARNESS HARNESS Study: switch to ATV/r + RAL Van Lunzen J. IAC 2014, Melbourne, Abs. LBPE19