ARV-trial.com Switch to ATV/r + RAL HARNESS Study 1

HARNESS Study: switch to ATV/r + RAL Design Randomisation 2 : 1 Open-label W24 W48 Adults Stable 2 NRTI + 3rd drug regimen No previous treatment failure HIV RNA < 40 c/mL > 3 months Switch for safety and/or tolerability issues No resistance to study medications HBs Ag negative ATV/r 300/100 mg qd + TDF/FTC N = 37 ATV/r 300/100 mg qd + RAL 400 mg bid N = 72 Objective Primary Endpoint: proportion with treatment success at W24 (HIV-1 RNA < 40 c/mL) No power calculation Descriptive analysis HARNESS Van Lunzen J. JAIDS 2016;71:538-43

Baseline characteristics and disposition HARNESS Study: switch to ATV/r + RAL Baseline characteristics and disposition ATV/r + TDF/FTC N = 37 ATV/r + RAL N = 72 Median age, years 44 Female 16% 19% Baseline CD4/mm3, mean 631 588 ARV regimens prior to switch PI/r + 2 NRTI NNRTI + 2 NRTI Other ARV regimens 54% 38% 8% 44% 51% 4% Discontinuation at W48, N Adverse event Lack of efficacy 5 1 16 4 3 HARNESS Van Lunzen J. JAIDS 2016;71:538-43

HARNESS Study: switch to ATV/r + RAL Efficacy and Safety results HIV RNA < 40 c/mL (ITT) Confirmed virologic rebound at W48, N ATV/r + TDF/FTC ATV/r + RAL N 1 9 Tested isolates 5 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 ATV/r + RAL ATV/r + TDF/FTC 100 94.6 80.6 20 40 60 80 % W24 (primary endpoint) W48 86.5 69.4 * 1 patient with both PI and INSTI mutations Virologic rebound 2 consecutive on-treatment HIV RNA > 40 c/mL Last on-treatment HIV RNA > 40 c/mL followed by discontinuation HARNESS Van Lunzen J. IAC 2014, Melbourne, Abs. LBPE19, Van Lunzen J. JAIDS 2016;71:538-43

Kaplan-Meier estimate HARNESS Study: switch to ATV/r + RAL Time to treatment failure (discontinuation of study therapy before W48 or virologic rebound before or at W48) Kaplan-Meier estimate % ATV/r + RAL ATV/r + TDF/FTC B/L 4 8 12 16 20 24 28 32 36 40 44 48 52 60 80 100 72 37 68 67 35 64 57 54 34 39 25 Number of patients at risk Week HARNESS Van Lunzen J. JAIDS 2016;71:538-43

HARNESS Study: switch to ATV/r + RAL Safety at W48, N ATV/r + TDF/FTC N = 37 ATV/r + RAL N = 72 Grade 3-4 AEs 5 13 Grade 2-4 drug-related AEs Grade 3-4 total bilirubin 8 3 12 Renal toxicity 6 1 Discontinuation due to AE 4 ATV and RAL geometric mean Ctrough values, available for most patients, were within therapeutic ranges over the study course HARNESS Van Lunzen J. JAIDS 2016;71:538-43

HARNESS Study: switch to ATV/r + RAL Conclusion In virologically suppressed patients on a triple-drug antiretroviral regimen, switching to ATV/r + RAL resulted in a lower maintenance of virologic suppression and a higher incidence of virologic rebound than in the ATV/r + TDF/FTC group at Week 24 and Week 48 In addition, tolerability issues and treatment discontinuation occurred more frequently and adherence was lower with ATV/r + RAL This pilot study did not support switching to ATV/r + RAL for safety/tolerability reasons in treatment-experienced patients with virological suppression HARNESS Van Lunzen J. JAIDS 2016;71:538-43