1. Switch to DRV/r + 3TC
DUAL Study

2. DUAL Study: switch to DRV/r + 3TC
Design
Randomisation*
1: 1
Open-label
W24
W48
DRV/r 800/ TC 300 QD
≥ 18 years
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
N = 126
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)
DUAL
Pulido F, Clin Infect Dis 2017; 65:2112-8

3. Baseline characteristics and disposition at W48
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
DUAL
Pulido F, Clin Infect Dis 2017; 65:2112-8

4. DUAL Study: switch to DRV/r + 3TC
Efficacy results (HIV RNA < 50 c/mL by ITT-e, snapshot) at W48
DRV/r + 2 NRTI
DRV/r + 3TC
Difference (95% IC)
- 3.8 ( ; 3.4)
100
88.9
92.7 20 40 60 80 %
HIV RNA < 50 c/mL
HIV RNA ≥ 50 c/mL
No virologic data 8 6 3 2
DUAL
Pulido F, Clin Infect Dis 2017; 65:2112-8

5. 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
1.2 (- 7.8 to 10.1)
DUAL
Pulido F, Clin Infect Dis 2017; 65:2112-8

6. 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
DRV/r + 2 NRTI
N = 123 N
HIV-1 RNA at failure (c/mL)
Protocol-defined virologic failure
W48 window
At baseline
At W24 4 2 1
130 ; 68 80
988, confirmed at 259
116 ; 79 -
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
2/3
0/2 2
1/2
1/1 (PRO: V10I, W71T, D76W ; no RT mutation)
DUAL
Pulido F, Clin Infect Dis 2017; 65:2112-8

7. DUAL Study: switch to DRV/r + 3TC
Adverse events, %
DRV/r + 3TC, N = 126
DRV/r + 2 NRTI, N = 123
≥ 1 adverse event 70 76
Grade 2-4 adverse events
11.9
14.6
AEs leading to discontinuation
0.8
(N = 1: hyperlipidemia)
1.6
(N = 2: diarrhea ; Hodgkin)
Serious adverse events
4.8
4.9
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 13 10 6 2 24 15 18 7 5
Grade 3-4 laboratory abnormalities
ALT > 5 x ULN AST > 5 x ULN
Total cholesterol > 300 mg/dL
Triglycerides > 750 mg/dL
3.2
3.3
2.4
DUAL
Pulido F, Clin Infect Dis 2017; 65:2112-8

8. (Cockroft-Gault), mL/min
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
Total cholesterol
LDL-C
HDL-C
Triglycerides
Total chol:
p < 0.001
p = 0.01
p = 0.83
p = 0.45
p = 0.93
p = 0.17
p = 0.42
p = 0.71 -8 -4 4 8 12 16 20 24
Dual-TDF at screen
Triple-TDF at screen
Dual-ABC at screen
Triple-ABC at screen
Dual (DRV/r + 3TC)
Triple (DRV/r + 2 NRTI) 1 2 3 4 5 6 7 8 9 10 -1
p = 0.19
p = 0.12
All
TDF
at screen
ABC
p = 0.96
DUAL
Pulido F, Clin Infect Dis 2017; 65:2112-8

9. 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
DUAL
Pulido F, Clin Infect Dis 2017; 65:2112-8