Switch to DRV/r + 3TC Dual Study Design and Results
"The DUAL study evaluated the non-inferiority of switching to DRV/r + 3TC regimen in HIV patients. Baseline characteristics, efficacy, and virologic outcomes at week 48 were assessed. The study aimed to maintain HIV RNA levels
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Switch to DRV/r + 3TC DUAL Study
DUAL Study: switch to DRV/r + 3TC Design Randomisation* 1: 1 Open-label W24 W48 N = 126 18 years DRV/r 800/100 + 3TC 300 QD Stable DRV/r 800/100 + TDF/FTC or ABC/3TC regimen 4 weeks HIV RNA < 50 c/mL > 6 months No resistance to DRV/r or 3TC/FTC HBs Ag negative DRV/r + ABC/3TC or TDF/FTC QD N = 123 * Randomisation was stratified by baseline nucleos(t)ides Objective Non inferiority of DRV/r + 3TC at W48: % HIV RNA < 50 c/mL by intention to treat-exposed, snapshot analysis (lower margin of the 2-sided 95% CI for the difference = - 12%, 80% power) Pulido F, Clin Infect Dis 2017; 65:2112-8 DUAL
DUAL Study: switch to DRV/r + 3TC Baseline characteristics and disposition at W48 DRV/r + 3TC N = 126 DRV/r + 2NRTI N = 123 Median age, years 44 43 Female, % 15 19 Baseline CD4/mm3, median 596 568 Nadir CD4/mm3, median 253 240 Duration of HIV RNA < 50 c/mL (weeks), median 79.5 113 (p = 0.014) HCV co-infection, % 25.4 22.8 N(t)RTI at baseline, % TDF/FTC ABC/3TC 74 26 76 24 Discontinued at W48, N (%) 9 (7.1) 4 (3.3) Adverse event / confirmed virologic failure 1 / 2 2 / 0 Withdrew consent / lost to follow-up 3 / 3 1 / 1 Pulido F, Clin Infect Dis 2017; 65:2112-8 DUAL
DUAL Study: switch to DRV/r + 3TC Efficacy results (HIV RNA < 50 c/mL by ITT-e, snapshot) at W48 DRV/r + 3TC DRV/r + 2 NRTI % 100 92.7 88.9 80 60 40 20 8 6 2 3 0 HIV RNA < 50 c/mL No virologic data HIV RNA 50 c/mL Difference (95% IC) - 3.8 (- 11.0 ; 3.4) Pulido F, Clin Infect Dis 2017; 65:2112-8 DUAL
DUAL Study: switch to DRV/r + 3TC Virologic outcome at W48 DRV/r + 3TC N = 126 DRV/r + 2 NRTI N = 123 % without virologic failure (observed data) 96.6 98.3 Difference (95% CI) - 1.7 (- 5.8 to 2.4) % with persistent virologic response (absence of protocol-defined virologic failure or blip) 85.7 84.5 Difference (95% CI) 1.2 (- 7.8 to 10.1) Pulido F, Clin Infect Dis 2017; 65:2112-8 DUAL
DUAL Study: switch to DRV/r + 3TC Virologic failure HIV RNA > 50 c/mL in the W48 window Discontinuation before W48 due to lack of efficacy Virologic failure and viral blips DRV/r + 3TC N = 126 HIV-1 RNA at failure (c/mL) DRV/r + 2 NRTI N = 123 HIV-1 RNA at failure (c/mL) N N Protocol-defined virologic failure W48 window At baseline At W24 4 2 1 1 2 2 0 0 130 ; 68 80 116 ; 79 - - 988, confirmed at 259 Viral load blips 14 17 HIV- 1 RNA > 400 c/mL and emergence of resistance DRV/r + 3TC DRV/r + 2 NRTI HIV RNA > 400 c/mL, N Samples amplified, N Emergence of resistance, N 3 2 2/3 0/2 1/2 1/1 (PRO: V10I, W71T, D76W ; no RT mutation) Pulido F, Clin Infect Dis 2017; 65:2112-8 DUAL
DUAL Study: switch to DRV/r + 3TC Adverse events, % DRV/r + 3TC, N = 126 70 11.9 0.8 (N = 1: hyperlipidemia) 4.8 DRV/r + 2 NRTI, N = 123 76 14.6 1.6 (N = 2: diarrhea ; Hodgkin) 4.9 1 adverse event Grade 2-4 adverse events AEs leading to discontinuation Serious adverse events Adverse events occurring in 5% of patients in either group Respiratory Infections Digestive Muscular or skeletal Neuropsychiatric Metabolic Genitourinary General disorders Ear, nose and throat Oral cavity Grade 3-4 laboratory abnormalities ALT > 5 x ULN AST > 5 x ULN Total cholesterol > 300 mg/dL Triglycerides > 750 mg/dL 25 17 14 13 10 10 6 6 6 2 3.2 0 0 3.2 0 24 15 18 18 10 7 5 6 7 6 3.3 0 0.8 2.4 0 Pulido F, Clin Infect Dis 2017; 65:2112-8 DUAL
DUAL Study: switch to DRV/r + 3TC Percent mean change in fasting lipids according to NRTI backbone at screen Mean change in eGFR (Cockroft-Gault), mL/min Dual (DRV/r + 3TC) Triple-TDF at screen Dual-TDF at screen Triple (DRV/r + 2 NRTI) 24 Dual-ABC at screen Triple-ABC at screen 10 9 20 8 p = 0.12 7 16 6 p = 0.19 p = 0.01 p < 0.001 p < 0.001 5 12 4 p = 0.71 p = 0.42 8 3 p = 0.45 2 p = 0.96 p = 0.83 p = 0.93 4 p = 0.17 p = 0.71 1 0 0 -1 All TDF ABC -4 at screen at screen -8 Total LDL-C HDL-C Total chol: HDL-C Triglycerides cholesterol Pulido F, Clin Infect Dis 2017; 65:2112-8 DUAL
DUAL Study: switch to DRV/r + 3TC Conclusion Dual therapy with DRV/r plus 3TC was non-inferior regarding maintenance of viral suppression and equally well tolerated as DRV/r plus TDF/FTC (or ABC/3TC) Persistent virological suppression was maintained after switching to dual therapy with DRV/r plus 3TC These results reinforce the efficacy of dual therapy with a fully active boosted PI and 3TC for maintenance of virological suppression Pulido F, Clin Infect Dis 2017; 65:2112-8 DUAL
