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Switch to ATV/r + RAL HARNESS Study HARNESS Study: switch to ATV/r + RAL Design Randomisation 2:1 Open-label 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 N = 37 W24 W48 ATV/r 300/100 mg qd + TDF/FTC 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 HARNESS Study: switch to ATV/r + RAL Baseline characteristics and disposition ATV/r + TDF/FTC N = 37 ATV/r + RAL N = 72 44 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% 5 1 1 16 4 3 Median age, years Discontinuation at W48, N Adverse event Lack of efficacy 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) ATV/r + TDF/FTC W24 (primary endpoint) ATV/r + RAL ATV/r + TDF/FTC ATV/r + RAL N 1 9 Tested isolates 0 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 W48 % 100 Confirmed virologic rebound at W48, N 94.6 86.5 80 80.6 69.4 60 * 1 patient with both PI and INSTI mutations 40 20 0 HARNESS Virologic rebound ̶ ̶ 2 consecutive on-treatment HIV RNA > 40 c/mL Last on-treatment HIV RNA > 40 c/mL followed by discontinuation Van Lunzen J. IAC 2014, Melbourne, Abs. LBPE19, Van Lunzen J. JAIDS 2016;71:538-43 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 % 100 80 60 40 ATV/r + TDF/FTC ATV/r + RAL 20 0 B/L 4 8 12 HARNESS 20 24 28 32 36 40 44 48 52 Week Number of patients at risk ATV/r + RAL ATV/r + TDF/FTC 16 72 37 68 37 67 35 64 35 57 35 54 34 39 25 Van Lunzen J. JAIDS 2016;71:538-43 HARNESS Study: switch to ATV/r + RAL Safety at W48, N ATV/r + TDF/FTC ATV/r + RAL N = 37 N = 72 Grade 3-4 AEs 5 13 Grade 2-4 drug-related AEs 8 12 Grade 3-4 total bilirubin 3 5 Renal toxicity 6 1 Discontinuation due to AE 1 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