NRTI-sparing SPARTAN PROGRESS RADAR NEAT001/ANRS 143 A4001078 VEMAN ARV-trial.com NRTI-sparing SPARTAN PROGRESS RADAR NEAT001/ANRS 143 A4001078 VEMAN MODERN 1

RADAR Study: DRV/r + RAL vs DRV/r + TDF/FTC 118 Design Randomisation 1 : 1 Open-label W96 N = 42 Age ≥ 18 years HIV+ Antiretroviral naive HIV-1 RNA ≥ 5 000 c/mL CD4 ≥ 100/mm3 No resistance to TDF, FTC or DRV DRV/r 800/100 qd + RAL 400 bid DRV/r + TDF/FTC N = 43 Objective Primary endpoint: time to loss of virologic response until W24 (ITT, TLOVR) Definition of failure: the earliest of any of the following events: death, permanent discontinuation of the study drug, loss to follow-up, or plasma HIV-1 RNA concentrations > 48 copies/ml obtained at 2 consecutive visits or one value > 48 copies/ml followed by permanent discontinuation of the study drug or loss to follow-up RADAR Bedimo R. PLOS One 2014;9:e106221

RADAR Study: DRV/r + RAL vs DRV/r + TDF/FTC Baseline characteristics (median), and disposition DRV/r + RAL N = 40 DRV/r + TDF/FTC N = 43 Age, years 44 39 Female 10% 5% CD4/mm3 249 201 HIV RNA, log10 copies/mL 4.69 4.92 Discontinuation by W48 N = 9 N = 6 Virologic efficacy DRV/r + RAL DRV/r + TDF/FTC HIV RNA < 48 c/mL at W24 (ITT, TLOVR) 75% 76.7% Mean time to loss of virologic response (ITT, TLOVR) 36.3 weeks 42.1 weeks HIV RNA < 48 c/mL at W48 (ITT, TLOVR) 60% 83.7% ≠ : - 23.7% (95% CI : - 42.9 to – 5.0) ; p = 0.016 HIV RNA < 48 c/mL at W48 (ITT, snapshot) 62.5% Resistance testing: no treatment-emergent resistance-associated mutations RADAR Bedimo R. PLOS One 2014;9:e106221

RADAR Study: DRV/r + RAL vs DRV/r + TDF/FTC Lipid parameters, renal function, body fat and bone mineral density Mean changes from baseline (95% CI) DRV/r + RAL N = 40 DRV/r + TDF/FTC N = 43 p Total cholesterol, mg/dL + 23.3 + 6.5 0.003 LDL-cholesterol, mg/dL + 11.2 + 3.3 NS HDL-cholesterol, mg/dL + 4.8 + 7.2 Triglycerides, mg/dL + 21.2 - 38.1 Total cholesterol:HDL cholesterol ratio - 0.25 - 0.71 eGFR (CKD-EPI formula), ml/min - 4.4 - 7.9 DXA analyses Subtotal BMD, g/cm2 Total BMD, g/cm2 Total fat, kg Total lean body mass, kg + 9.2 + 11.3 + 3.13 + 1.48 - 7 - 6.9 + 1.8 + 0.6 0.002 0.013 0.084 Grade 3 or higher clinical or laboratory adverse event: 5 in the RAL arm vs 2 in the TDF/FTC arm RADAR Bedimo R. PLOS One 2014;9:e106221

RADAR Study: DRV/r + RAL vs DRV/r + TDF/FTC Conclusion The NRTI-sparing regimen RAL+ DRV/r did not achieve similar week 48 virologic efficacy compared with TDF/FTC + DRV/r, but was better with regard to markers of bone health The two regimens achieved comparable immunologic response Patients in the TDF/FTC arm had smaller increases in total cholesterol Limitations Small sample size Unpowered to establish non-inferiority AEs self-reported, open-label unblinded design No site-specific BMD evaluation RADAR Bedimo R. PLOS One 2014;9:e106221