1. Comparison of INSTI vs PI
ARV-trial.com
Comparison of INSTI vs PI
FLAMINGO GS
ACTG A5257
WAVES
ARIA 1

2. ARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
ARV-trial.com
ARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
Design
Randomisation*
1 : 1
Open label
W48
Women ≥ 18 years
ARV-naive
HIV RNA > 500 c/mL
Any CD4 cell count
HLA-B*5701 negative
No major resistance-associated
mutations
Hepatitis B negative
N = 248
DTG/ABC/3TC QD
N = 247
ATV + r 300/100 mg + FTC/TDF QD
* Randomisation was stratified by HIV RNA (≤ or > c/mL) and CD4 (≤ or > 350/mm3)
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)
ARIA
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3. ARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
ARV-trial.com
ARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
Baseline characteristics and patient disposition
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
HIV RNA (log10 c/mL), median
4.41
4.43
HIV RNA > c/mL, % 28 27
CD4 cell count (/mm3), median
340
350
CD4 < 350 per mm3, % 52 50
Hepatitis C coinfection, % 6 9
Discontinuation by W48, N (%)
42 (17%)
55 (22%)
For lack of efficacy, N 5
For adverse event, N 10 18
Lost to follow-up / Withdrew consent, N
11 / 5
13 / 7
Pregnancy, N 8
Protocol deviation/ Investigator decision, N
5 / 1
5 / 0
ARIA
Orrell C. Lancet HIV :e536-46 3

4. ARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
ARV-trial.com
ARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
Response to treatment (HIV-1 RNA < 50 c/mL) at week 48, ITT-E
By baseline strata
DTG/ABC/3TC (N = 248)
ATV + r + FTC/TDF (N = 247) 25 50
100 75
81.9
71.3
Adjusted difference
(95% CI) =
10.5 % (3.1 ; 17.8)
p = 0.005 6 14
Virologic success
Virologic non-response % 12 15
No virologic
data
DTG/ABC/3TC
ATV + r + FTC/TDF
HIV RNA ≤ 105 c/mL
82.6 74
HIV RNA > 105 c/mL
79.7
63.6
CD4 ≤ 350/mm3
85.4
71.8
CD4 > 350/mm3 78
70.7
Emergence of resistance
Confirmed virologic failure (HIV RNA ≥ 400 c/mL): 6 DTG/ABC/3TC vs 4 ATV + r + FTC/TDF
Mutations emergence at failure
DTG/ABC/3TC, N = 2 (K219K/Q, E138E/G)
ATV + r + FTC/TDF, N = 1 (M184V)
ARIA
Orrell C. Lancet HIV :e536-46 4

5. ARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
ARV-trial.com
ARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
Response to treatment (HIV-1 RNA < 50 c/mL) at W48, per protocol
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 % 8 13
No virologic
data
ARIA
Orrell C. Lancet HIV :e536-46 5

6. ARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
ARV-trial.com
ARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
Adverse events
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)
5 (2)
121 (49)
35 (14)
18 (7)
15 (6)
14 (6)
13 (5)
Serious adverse events, N (%)
20 (8)
Fatal adverse events, N
1 (unrelated)
Drug-related serious adverse events, N
3 (1)
Discontinuation due to adverse events, N (%)
10 (4)
17 (7)
Psychiatric adverse events, N (%)
Insomnia
Anxiety
Depression
Suicidal ideation
Depressed mood
Abnormal dreams
2 (< 1)
9 (4)
7 (3)
ARIA
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7. ARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
ARV-trial.com
ARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
Changes in laboratory parameters at W48
DTG/ABC/3TC
N = 248
ATV + r + FTC/TDF
N = 247 p
ALT ≥ 3 x ULN, % 2
1 case > 20 x ULN
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, N 3 1
Total cholesterol: HDL-cholesterol ratio
Adjusted mean difference :
(95% CI: to 0.101) ns
Triglycerides, mmol/L
Adjusted mean difference :
(95% CI: to 0.107)
Bone-related markers, W48: baseline ratio
Bone-specific alkaline phosphatase
Type I collagen C-telopeptides
Osteocalcin
Procollagen 1 N-terminal propeptide
Vitamin D
1.188
1.257
1.282
1.214
0.987
1.629
1.918
2.039
1.752
1.158
< 0.001
ARIA
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8. ARIA Study: DTG/ABC/3TC QD vs ATV + r + FTC/TDF QD in Women
ARV-trial.com
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 treatment
HIV 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 arm
DTG/ABC/3TC had a favorable safety profile compared to ATV + r + TDF/FTC
ARIA
Orrell C. Lancet HIV :e536-46 8