FLAMINGO GS2360103 ACTG A5257 WAVES ARIA Design Objective Non inferiority of DTGABC3TC at W48 HIV RNA lt 50 cmL by intention to treat snapshot analysis lower margin of the 2sided 95 CI for the difference 12 ID: 526297
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Slide1
Comparison of INSTI vs PI
FLAMINGO
GS-236-0103
ACTG A5257
WAVES
ARIA Slide2
Design
Objective
Non inferiority of DTG/ABC/3TC at W48: % HIV RNA < 50 c/mL by intention
to treat, snapshot analysis (lower margin of the 2-sided 95% CI for the difference = - 12%, 90% power)
DTG/ABC/3TC QD
ATV + r 300/100 mg + FTC/TDF QD
Randomisation*
1 : 1Open label
Women ≥ 18 yearsARV-naiveHIV RNA > 500 c/mLAny CD4 cell countHLA-B*5701 negativeNo major resistance-associatedmutationsHepatitis B negative
* Randomisation was stratified by HIV RNA (≤ or > 100 000 c/mL) and CD4 (≤ or > 350/mm3)
ARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
N = 247
N = 248
W48
ARIA
Orrell
C. Lancet HIV 2017 4:e536-46Slide3
ARIA
Study
: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
DTG/ABC/3TC
N = 248
ATV + r + FTC/TDF
N = 247
Mean age, years
38.1
37.8
White / Black / Asian, %
46 / 41 / 9
43 / 44 / 9
AIDS, %
4
4
HIV RNA (log
10
c/mL), median
4.41
4.43HIV RNA > 100 000 c/mL, %2827CD4 cell count (/mm3), median340350CD4 < 350 per mm3, %5250Hepatitis C coinfection, %69Discontinuation by W48, N (%)42 (17%)55 (22%)For lack of efficacy, N54For adverse event, N1018Lost to follow-up / Withdrew consent, N11 / 513 / 7Pregnancy, N58Protocol deviation/ Investigator decision, N5 / 15 / 0
ARIA
Baseline characteristics and patient disposition
Orrell
C. Lancet HIV 2017 4:e536-46Slide4
Response to treatment (HIV-1 RNA < 50 c/mL) at week 48, ITT-E
DTG/ABC/3TC (N = 248)
ATV + r + FTC/TDF (N = 247)
25
50
100
75
81.9
71.3Adjusted difference(95% CI) =
10.5 % (3.1 ; 17.8)p = 0.005
6
14
Virologic
success
Virologic
non-response
%
0
12
15
No virologicdataBy baseline strataARIAARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in WomenEmergence of resistanceConfirmed virologic failure (HIV RNA ≥ 400 c/mL):6 DTG/ABC/3TC vs 4 ATV + r + FTC/TDFMutations emergence at failureDTG/ABC/3TC, N = 2 (K219K/Q, E138E/G)ATV + r + FTC/TDF, N = 1 (M184V)DTG/ABC/3TCATV + r + FTC/TDFHIV RNA ≤ 105 c/mL82.674HIV RNA > 105 c/mL79.763.6CD4 ≤ 350/mm385.471.8CD4 > 350/mm37870.7Orrell C. Lancet HIV 2017 4:e536-46Slide5
DTG/ABC/3TC (N = 230)
ATV + r + FTC/TDF (N = 225)
25
50
100
75
86
76
Adjusted difference(95% CI) = 9.7% (2.6 ; 16.8)p = 0.005
6
11
Virologic
success
Virologic
non-response
%0
8
13
No
virologic
dataARIAARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in WomenResponse to treatment (HIV-1 RNA < 50 c/mL) at W48, per protocolOrrell C. Lancet HIV 2017 4:e536-46Slide6
DTG/ABC/3TC
ATV + r + FTC/TDF
Grade 2 to 4 adverse events, N (%)
115 (46)
137 (55)
Drug-related adverse events (≥ 5% in either arm), N (%)
Nausea
Diarrhea
Dyspepsia
Ocular icterus
Headache
Jaundice
83 (33)
31 (13)
12 (5)
4 (2)
0
5 (2)
0
121 (49)
35 (14)18 (7)15 (6)18 (7)14 (6)13 (5)Serious adverse events, N (%)12 (5)20 (8)Fatal adverse events, N1 (unrelated)0Drug-related serious adverse events, N03 (1)Discontinuation due to adverse events, N (%)10 (4)17 (7)Psychiatric adverse events, N (%)InsomniaAnxietyDepressionSuicidal ideationDepressed moodAbnormal dreams35 (14)10 (4)5 (2)5 (2)4 (2)3 (1)2 (< 1)35 (14)9 (4)7 (3)7 (3)3 (1)4 (2)2 (< 1)Adverse eventsARIAARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in WomenOrrell C. Lancet HIV 2017 4:e536-46Slide7
DTG/ABC/3TC
N = 248
ATV + r + FTC/TDF
N = 247
p
ALT ≥ 3 x ULN, %
2
1 case >
20 x ULN
2
Serum creatinine, mean change
+ 9.29
+ 5.86
Urine
albumin:creatinine
ratio (g/
moL
), median change
- 0.10
0.00
Creatinine phosphokinase, grade 3-4, N31Total cholesterol: HDL-cholesterol ratioAdjusted mean difference : - 0.106 (95% CI: - 0.313 to 0.101)nsTriglycerides, mmol/LAdjusted mean difference : - 0.026 (95% CI: - 0.159 to 0.107)nsBone-related markers, W48: baseline ratioBone-specific alkaline phosphataseType I collagen C-telopeptidesOsteocalcinProcollagen 1 N-terminal propeptideVitamin D1.1881.2571.2821.2140.9871.6291.9182.0391.7521.158< 0.001< 0.001< 0.001< 0.001< 0.001Changes in laboratory parameters at W48 ARIAARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in WomenOrrell C. Lancet HIV 2017 4:e536-46Slide8
ARIA
Study
: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
Conclusion
In treatment-naive women, DTG/ABC/3TC was superior to ATV + r + TDF/FTC at 48 weeks of treatmentHIV RNA < 50 c/mL (ITT-E, snapshot): 82% vs 71%Adjusted difference 10.5%, 95% CI: 3.1% to 17.8%, p = 0.005
Difference driven by lower rate of virologic non-response and fewer discontinuations due to adverse events in DTG armDTG/ABC/3TC had a favorable safety profile compared to ATV + r + TDF/FTC ARIAOrrell C. Lancet HIV 2017 4:e536-46