ENCORE EFV vs RPV ECHOTHRIVE STAR EFV vs ETR SENSE DOR vs EFV DRIVEAHEAD Design Objectives Non inferiority of DOR at W48 HIV RNA lt 50 cmL by intention to treat snapshot analysis lower margin of the 95 CI for the difference 10 ID: 757223
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Slide1
Comparison of NNRTI vs NNRTI
ENCORE
EFV vs RPV
ECHO-THRIVE
STAR
EFV vs ETR
SENSE
DOR vs EFV
DRIVE-AHEADSlide2
Design
Objectives
Non inferiority of DOR at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (lower margin of the 95% CI for the difference = - 10%,
90% power)
Superiority of DOR for neuropsychiatric adverse events by W48
DOR 100 mg/3TC/TDF QD + placebo
EFV/FTC/TDF + placebo
Randomisation*1 : 1Double-blind
* Randomisation was stratified by HIV RNA (< or > 100 000 c/mL) at screening and chronic hepatitis B or C
N = 364
N = 364
W48
W96
DRIVE-AHEAD
Study
: DOR/3TC/TDF vs EFV/FTC/TDF
Squires KE. IAS 2017, Abs. TUAB0104LB
DRIVE-AHEAD
>
18 years
ARV-naïve
HIV RNA
>
1 000 c/mLAny CD4 cell counteGFR (CG) ≥ 50 mL/minNo primary resistance to DOR, EFV, NRTI
DOR/3TC/TDF : 1 tablet
qd
as STRSlide3
DOR/3TC/TDF
(N = 364)
EFV/FTC/TDF
(N = 364)
Median age, years
32
30
Female, %
16
15
AIDS, %
13
15
HIV RNA (log
10
c/mL), mean
4.4
4.5
HIV RNA > 100 000 c/mL, %
20
23
CD4 cell count (/mm
3
), mean
435
416CD4 < 200/mm3, %1213Discontinuation at W48, N (%)Lack of efficacy, NAdverse event, NDeath, NLost to follow-up / Consent withdrawal, NNon-compliance / Other, N51 (14%)181016 / 81 / 761 (17%)102337 / 112 / 5
Baseline characteristics and patient disposition
DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF
Squires KE. IAS 2017, Abs. TUAB0104LB
DRIVE-AHEADSlide4
EFV
DOR
0
‒ 10%
+ 10%
9.0
-2.0
3.5
Difference (95 % CI)
EFV/FTC/TDF (N = 364)
84
11
5
81
10
9
0
20
40
60
80
100
Virologic
response
Virologic
non-responseNo dataDOR/3TC/TDF (N = 364)%58Primary endpoint: HIV RNA < 50 c/mL at W48 (ITT, snapshot)CD4 increase at W48 (ITT, NC = F)DOR: + 198/mm3EFV: + 188/mm3HIV RNA < 50 c/mL at W48 (observed failure approach)Baseline HIV RNA ≤ 100 000 c/mL: DOR: 90.6% vs EFV: 91.1 %Baseline HIV RNA > 100 000 c/mL: DOR: 81.2 % vs EFV: 80.8 %DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDFSquires KE. IAS 2017, Abs. TUAB0104LBDRIVE-AHEADSlide5
DOR /3TC/TDF
(N = 364)
EFV/FTC/TDF
(N = 364)
Virologic failure, N
22 (6.0%)
14 (3.8%)
Non response / Rebound
6
16
4
10
Discontinuations without PDVF, N
35
50
Genotype successfully performed, N
Primary NNRTI resistance
Primary NRTI resistance
23
6 *
5 *
24
12 **
5 **
Definition
Non response: HIV RNA ≥ 200 c/mL at W24 or W36 or confirmed HIV RNA ≥ 50 c/mL at W48Rebound: confirmed HIV RNA ≥ 50 c/mL after obtaining HIV RNA < 50 c/mL60Protocol-defined virologic failures (PDVF)* NNRTI mutations : Y188L; V106I, F227C; V106V/I, H221H/Y, F227C; F227C; V106A, P225H, Y318Y/F; V106M/T, F227C/R ; NRTI mutations : M41L, M184V; M184V; M184V; K65R; K65K/R, M184V** NNRTI mutations : K103N; K103N, E138E/G; K103N; G190E; K103N; K103N, M230L; G190E; K103N, V108V/I, T369T/A/I/V; K103N; K103N; K101K/N, K103N, P225P/H ; NRTI mutations : V118I, M184V; M184V; M184V; M184V, K219K/E; K65K/R, M184M/IDRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDFSquires KE. IAS 2017, Abs. TUAB0104LBDRIVE-AHEADSlide6
DOR/3TC/TDF
(N = 364)
EFV/FTC/TDF
(N = 364)
Drug-related adverse event
31
63
Serious adverse event
4
6
Discontinuation due to
adverse event
Drug-related
3
2
7
6
Discontinuation due to serious adverse event
Drug-related
1
< 1
1
1
Adverse event in
≥ 10% in either groupHeadacheDiarrheaNasopharyngitisDizzinessNauseaAbnormal dreamsRash13111198551214937111212Grade 3-4 laboratory abnormalitiesFasting LDL-cholesterolFasting triglyceridesCreatinineAST / ALTLipaseCreatine kinase
< 1
1
2
< 1 / 1
1
3
2
3
1
1 / 1
1
3
62
Adverse events, %
DRIVE-AHEAD
Study
: DOR/3TC/TDF vs EFV/FTC/TDF
Squires KE. IAS 2017, Abs. TUAB0104LB
DRIVE-AHEADSlide7
% with Predefined Neuropsychiatric Adverse Events at W48
DRIVE-AHEAD
Study
: DOR/3TC/TDF vs EFV/FTC/TDF
Squires KE. IAS 2017, Abs. TUAB0104LB
DRIVE-AHEAD
DOR/3TC/TDF
EFV/FTC/TDF
0
10
20
30
40
Dizziness
Sleep
disorders and
disturbances
Altered
sensorium
Depression
and suicide/
self-injury
Psychosis
and psychotic
disorders
8.837.112.125.54.48.24.16.60.31.1p < 0.001p < 0.001p = 0,033%Slide8
Fasting Lipids (mg/
dL
): Change from Baseline at W48
DRIVE-AHEAD
Study
: DOR/3TC/TDF vs EFV/FTC/TDF
Squires KE. IAS 2017, Abs. TUAB0104LB
DRIVE-AHEAD
-15
LDL-C
p < 0,0001
Non-HDL-C
Cholesterol
Triglycerides
HDL-C
DOR/3TC/TDF
EFV/FTC/TDF
-10
-5
0
5
10
15
20
25
p < 0,0001-1.68.7-3.813.3-2.021.8-12.422.01.98.5Slide9
Conclusion at week 48
In treatment-naïve adults with HIV-1 infection, DOR/3TC/TDF administered once daily demonstrated:
Antiviral potency with non-inferior efficacy to EFV/FTC/TDF regardless of baseline HIV-1 RNA
Low rate of resistance, with only 1.6% of participants developing resistance to any study drug through W48
DOR/3TC/TDF was generally well tolerated and safe:Neuropsychiatric profile superior to EFV/FTC/TDF, as measured by lower proportion of participants with neuropsychiatric adverse events in categories of dizziness, sleep disorders and disturbances, and altered sensoriumLipid profile superior to EFV/FTC/TDF, as assessed by difference from baseline in fasting LDL-C and non-HDL-CDRIVE-AHEAD Study
: DOR/3TC/TDF vs EFV/FTC/TDFSquires KE. IAS 2017, Abs. TUAB0104LB
DRIVE-AHEAD