Embed Size (px)
Citation preview
Comparison of NNRTI vs NNRTI
ENCORE EFV vs RPV
– ECHO-THRIVE– STAR
EFV vs ETR– SENSE
Design
Objective– Non inferiority of RPV/FTC/TDF at W48: % HIV RNA < 50 c/mL by intention to
treat, snapshot analysis (1-sided significance level of 2.5%, lower margin of the 97.5% CI for the difference = -12%, 95% power)
RPV/FTC/TDF QD STR
EFV/FTC/TDF QD STR
Randomisation*1 : 1
Open-label
Randomisation*1 : 1
Open-label
> 18 yearsARV-naïve
HIV RNA > 2,500 c/mLAny CD4 cell counteGFR > 50 mL/min
Sensitivity to EFV, FTC and TDF on genotype
No RPV resistance mutations**
> 18 yearsARV-naïve
HIV RNA > 2,500 c/mLAny CD4 cell counteGFR > 50 mL/min
Sensitivity to EFV, FTC and TDF on genotype
No RPV resistance mutations**
* Randomisation was stratified by HIV RNA (< or > 100,000 c/mL)** K101E/P, E138A/G/K/Q/R, Y181C/I/V, H221Y
N = 392
N = 394
W48W48 W96W96
Concomitant use of proton pump inhibitors was not allowed
Cohen C. AIDS 2014;28:989-97
STAR Study: RPV/FTC/TDF vs EFV/FTC/TDF
STAR
RPV/FTC/TDFN = 394
EFV/FTC/TDFN = 392
Median age, years 37 35
Female 7% 7%
HIV RNA (log10 c/mL), median 4.8 4.8
HIV RNA > 100,000 c/mL 34% 36%
CD4 cell count (/mm3), mean 396 385
Discontinuation by W48 54 (13.7%) 72 (18.4%)
For lack of efficacy N = 12 N = 3
For adverse event N = 10 N = 34
Lost to follow-up N = 15 N = 10
Non compliance N = 6 N = 4
Withdrew consent N = 5 N = 13
Protocol violation N = 1 N = 1
Pregnancy N = 2 -
Investigator’s decision N = 3 N = 3
Death - N = 1
Baseline characteristics and patient disposition
Cohen C. AIDS 2014;28:989-97
STAR Study: RPV/FTC/TDF vs EFV/FTC/TDF
STAR
Response to treatment (HIV RNA < 50 c/mL) at week 48
Median CD4/mm3 increase at W48 : + 200 RPV/FTC/TDF vs + 191 EFV/FTC/TDFCohen C. AIDS 2014;28:989-97
STAR Study: RPV/FTC/TDF vs EFV/FTC/TDF
STAR
25
50
100
75
85.881.6
Adjusted difference(95% CI) =
4.1% (-1.1 ; 9.2)
79.9 81.7
Adjusted difference(95% CI) =
5.9% (0.6 ; 11.2)
ITT, snapshot ITT snapshot, by baseline HIV-1 RNA
RPV/FTC/TDF EFV/FTC/TDF
Primary analysis%
0
88.881.6
85.379.6
> 100,000 c/mL < 100,000 c/mL
ITT, TLOVR
Difference (95% CI) = 7.2% (1.1 ; 13.4)
Difference (95% CI) = -1.8% (-11.1 ; 7.5)
RPV/FTC/TDF EFV/FTC/TDFResistance analysis population* 20 (5%) 7 (2%)
Resistance to antiretrovirals 17 (4.3%) 3 (0.8%)
In patients with baseline HIV RNA < 100,000 c/mL 1.9% 0.8%
In patients with baseline HIV RNA > 100,000 c/mL 9.0% 0.7%
Any primary NNRTI resistance 16 3
Y181C/I 8 -
E138K/Q 6 -
K101E 5 -
K103N - 1
Y188L - 1
G190E/Q - 1
Any primary NRTI resistance 16 1
M184V/I 15 1
K65R/N 3 0
Resistance analysis through week 48
* HIV RNA > 400 c/mL and suboptimal virologic response (confirmed < 1 log10 c/mL decrease in HIV RNA at W8) virologic rebound (2 consecutive visits with HIV RNA > 50 c/mL after achieving < 50 c/mL, 2 consecutive visits with > 1 log10 c/mL increase in HIV RNA from the nadir) or HIV RNA > 400 c/mL at W48 or last visit
Cohen C. AIDS 2014;28:989-97
STAR Study: RPV/FTC/TDF vs EFV/FTC/TDF
STAR
RPV/FTC/TDF EFV/FTC/TDFNervous system events 29.7% 50.5%
Dizziness 6.6% 22.2%Insomnia 9.6% 14.0%Somnolence 2.5% 13.5%Headache 12.4% 13.5%
Psychiatric events 15.7% 37.5%Abnormal dreams 5.8% 24.5%Depression 6.6% 8.9%Anxiety 5.1% 8.4%
Rash events 17.3% 21.2%Folliculitis 5.3% 1.0%Rash 6.1% 12.0%
Treatment-emergent adverse events of specific interest in > 5% in either arm
RPV/FTC/TDF EFV/FTC/TDFGrade 3-4 treatment-emergent adverse events 7.4% 13.8%
Related to study drug 1.8% 4.8%
Safety through week 48
Cohen C. AIDS 2014;28:989-97
STAR Study: RPV/FTC/TDF vs EFV/FTC/TDF
STAR
Mean changes in fasting lipids (mg/dL) at week 48
Cohen C. AIDS 2014;28:989-97
STAR Study: RPV/FTC/TDF vs EFV/FTC/TDF
STAR
Change in total cholesterol/HDL-cholesterol at week 48 was -0.2 in both arms
P<0.001 for all between treatment groups using ANOVA
Mean baseline values (mg/dL)
164 163 104 103 121 129 44 44
RPV/FTC/TDF EFV/FTC/TDF
Conclusion at week 48– In treatment-naive HIV-infected patients, RPV/FTC/TDF demonstrated
non inferior efficacy and improved tolerability compared with EFV/FTC/TDF, at week 48
• RPV/FTC/TDF was statistically significant superiority in efficacy for patients
with baseline HIV-1 RNA ≤ 100,000 c/mL• Virologic efficacy was similar for patients with baseline HIV-1 RNA
> 100,000 c/mL– More discontinuations due to adverse events in the EFV/FTC/TDF arm– Significantly lower rates of nervous system and psychiatric adverse
events in the RPV/FTC/TDF arm than in the EFV/FTC/TDF arm• Differences primarily due to dizziness and abnormal dreams
– Virologic failures rates were similar between the 2 treatment arms• A greater proportion of patients in the RPV/FTC/TDF arm developed
primary emergent NRTI or NNRTI resistance mutations at virologic failure
Cohen C. AIDS 2014;28:989-97
STAR Study: RPV/FTC/TDF vs EFV/FTC/TDF
STAR
STAR Study: RPV/FTC/TDF vs EFV/FTC/TDF
Cohen C. IAC 2014 Melbourne, Abs. WEPE064STAR
Response to treatment (HIV RNA < 50 c/mL) at week 96
W48
W96
W48
W96
1.1 7.2 13.4
15.17.60.2
7.5-1.8-11.1
-8.7 1.5 11.6
12%0-12%
P=0.046
P=0.78
> 100,000 c/mL
< 100,000 c/mL
HIV RNA at baseline
FavorsEFV/FTC/TDF
FavorsRPV/FTC/TDF
0
20
40
60
80
100
231/260
204/250
205/260
178/250
107/134
116/142
102/134
106/142
RPV/FTC/TDF at W48
RPV/FTC/TDF at W96
EFV/FTC/TDF at W48
EFV/FTC/TDF at W96
8982
79
71
80 8276 75
< 100,000 c/mL > 100,000 c/mL
Baseline HIV RNA
%
Resistance analysis at week 96
STAR Study: RPV/FTC/TDF vs EFV/FTC/TDF
Cohen C. IAC 2014 Melbourne, Abs. WEPE064STAR
RPV/FTC/TDF (N = 394) EFV/FTC/TDF (N = 392)
Baseline-W48 W48-W96 Baseline-W48 W48-W96
Subjects in the Resistance Analysis Population 20 (5%) +4 (1%) 7 (1.8%) +2 (0.5%)
Subjects with Resistance Data 20 (5%) +4 (1%) 7 (1.8%) +2 (0.5%)
Subjects with Resistance to ARVs 17 (4%) +4 (1%) 3 (0.8%) +1 (0.3%)
Any primary NNRTI-RKey NNRTI-R
16 (4%)E138K/Q (N=6)Y181C/I (N=8)K101E (N=5)
+4 (1%)+4+0+0
3 (1%)K103N (N=1)Y188L (N=1)
G190E/Q (N=1)M230L (N=0)
+1 (0.3%)+0+0+0+1
Any primary NRTI-RKey NRTI-R
16 (4%)M184V/I (N=15)K65R/N (N=3)
+4 (1%)+4+0
1 (0.3%)M1841 (N=1)
+1 (0.3%)+1
With baseline HIV RNA< 100,000 c/mL> 100,000 c/mL
5/260 (2%)12/134 (9%)
+4 (1%)+0
2/250 (1%)1/142 (0.7%)
+1 (0.4%)+0
