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

2. MODERN Study: MVC QD + DRV/r vs TDF/FTC + DRV/r
ARV-trial.com
MODERN Study: MVC QD + DRV/r vs TDF/FTC + DRV/r
Design
Randomisation
1 : 1
to tropism assay
Randomisation
double-blind, 1 : 1
to treatment
W48
W96
Trofile
Phenotypic
Assay
MVC 150 mg QD + TDF/FTC placebo +
DRV 800 mg QD + RTV 100 mg QD
> 18 years
ARV-naïve
HIV RNA > 1,000 c/mL
CD4 > 100/mm3
No resistance
to DRV, TDF, FTC
N = 396
CCR5
tropic
TDF/FTC QD + MVC placebo +
DRV 800 mg QD + RTV 100 mg QD
N = 1423
MVC 150 mg QD + TDF/FTC placebo +
DRV 800 mg QD + RTV 100 mg QD
N = 401
CCR5
tropic
Genotypic
Tropism
Assay
TDF/FTC QD + MVC placebo +
DRV 800 mg QD + RTV 100 mg QD
Objective
Non inferiority of MVC at W48: % HIV RNA < 50 c/mL by intention to treat, missing, switch, discontinuation = failure, snapshot analysis (lower margin of the 95% CI for the difference = -10%)
MODERN
Stellbrink HJ. AIDS 2016; 30: 2

3. MODERN Study: MVC QD + DRV/r vs TDF/FTC + DRV/r
ARV-trial.com
MODERN Study: MVC QD + DRV/r vs TDF/FTC + DRV/r
Baseline characteristics and patient disposition
MVC + DRV/r
N = 396
TDF/FTC + DRV/r
N = 401
Median age, years 37 35
Female
9.1%
8.5%
HIV RNA (log10 c/mL), mean
4.42
HIV RNA > 100,000 c/mL
21%
CD4 cell count (/mm3), median
352
345
CD4 < 200 per mm3
9.5%
11%
B subtype
86.4%
88.3%
Discontinuation by W48, n (%)
73 (18.4%)
50 (12.5%)
For insufficient response 33 8
For adverse event 19 18
Lost to follow-up 7
Withdrew consent / other
6 / 7
8 / 9
Study was terminated early upon recommendation of IDMC
MODERN
Stellbrink HJ. IAC 2014, Abs. TUAB0101 3

4. MODERN Study: MVC QD + DRV/r vs TDF/FTC + DRV/r
ARV-trial.com
MODERN Study: MVC QD + DRV/r vs TDF/FTC + DRV/r
Response to treatment at week 48
HIV RNA < 50 c/mL at week 48, ITT snapshot %
MVC + DRV/r
TDF/FTC + DRV/r
100
88.7
86.8
80.7
79.7
77.3
78.7
74.4 75
66.2 50 25
306/
396
348/
401
146/
181
160/ 215
259/ 325
289/ 326
47/ 71
59/ 75
Overall
Genotype
Phenotype
Baseline HIV RNA (c/mL)
Adjusted difference
(95% CI) =
-9.5 % ( ; -4.2)
Adjusted difference
(95% CI) =
6.9 % (- 1.3 ; 15)
< 100,000
≥ 100,000
Mean CD4+ cell count//mm3 changes at W48 : MVC = vs TDF/FTC = + 194
MODERN
Stellbrink HJ. AIDS 2016; 30: 4

5. MODERN Study: MVC QD + DRV/r vs TDF/FTC + DRV/r
ARV-trial.com
MODERN Study: MVC QD + DRV/r vs TDF/FTC + DRV/r
Protocol-defined treatment failure (PDTF) criteria:
Decrease in plasma HIV RNA < 1 log10 from baseline after W4, unless plasma HIV RNA is < 50 c/mL, or
Plasma HIV RNA > 1 log10 c/mL above the nadir value after W4, or
Plasma HIV RNA ≥ 50 c/mL at any time after W24, or
Plasma HIV RNA ≥ 50 c/mL after suppression to < 50 c/mL on 2 consecutive visits, or
Decrease in plasma HIV RNA < 2 log10 c/mL from baseline on or after W12, unless plasma HIV RNA is < 50 c/mL (amendment 2), and < 400 c/mL (amendment 3)
All PDTFs required confirmation within 28 days of the initial event
MVC + DRV/r
TDF/FTC + DRV/r
PDTF, n (%)
40 * (10.1%)
13 * (3.2%)
HIV RNA < 400 c/mL at PDTF
27 (68%)
11 (85%)
Emergence of resistance mutations
* 3 in each group had HIV RNA < 400 c/mL and showed a response at W48
MODERN
Stellbrink HJ. AIDS 2016; 30: 5

6. MODERN Study: MVC QD + DRV/r vs TDF/FTC + DRV/r
ARV-trial.com
MODERN Study: MVC QD + DRV/r vs TDF/FTC + DRV/r
Treatment-emergent adverse events at week 48
MVC + DRV/r
TDF/FTC + DRV/r
AE in > 5% of subjects in either group, %
Diarrhea 23 34
Nasopharyngitis 12 14
Upper respiratory tract infection 10 11
Rash 8
Nausea 9
Fatigue 7
Cough
Bronchitis 6
Gastroenteritis 4
Depression
Insomnia
Malignancies
N = 9 (2.3%)
N = 3 (0.7%)
Grade 3-4 laboratory abnormalities, %
ALT
2.3
1.5
Total bilirubin
0.8
0.3
Creatine kinase
4.5
5.5
LDL-cholesterol
12.6
6.0
MODERN
Stellbrink HJ. AIDS 2016; 30: 6

7. MODERN Study: MVC QD + DRV/r vs TDF/FTC + DRV/r
ARV-trial.com
MODERN Study: MVC QD + DRV/r vs TDF/FTC + DRV/r
Conclusion
MVC 150 mg QD + DRV/r QD was statistically inferior to TDF/FTC + DRV/r QD in antiretroviral-naïve subjects over 48 weeks
Lower rate of virologic suppression
IDMC recommended study termination
The majority of failure had HIV RNA < 400 c/mL
There was no treatment-emergent resistance in either arm
Safety was comparable
MVC 150 mg QD in dual therapy with DRV/r QD cannot be recommended as first-line antiretroviral therapy
MODERN
Stellbrink HJ. AIDS 2016; 30: 7