1. Switch to DTG-containing regimen
STRIIVING Study
NEAT 022 Study

2. NEAT 022 Study: Switch to DTG vs continuation of PI/r in patients with high cardiovascular risk
Design
Randomisation
stratified by country
1 : 1
Open label
W48
W96
6 European countries
HIV+ ≥ 50 years or
≥ 18 years with Framingham
risk score > 10% at 10 years
On PI/r + 2 NRTIs > 6 months
HIV RNA < 50 c/mL ≥ 6 months
No documented primary
resistance mutations
Switch to DTG + 2 NRTIs (unchanged)
N = 205
N = 210
Continuation
PI/r + 2 NRTIs (unchanged)
Switch
DTG + 2 NRTIs
Primary endpoints
Proportion of patients with virological success at W48 (no consecutive HIV-1 RNA > 50 c/mL and no treatment discontinuation): non-inferiority of DTG, by ITT, Kaplan-Meier analysis; lower limit of the 95% CI for the difference = - 10%, power 90%
Mean percentage changes in fasting lipid total cholesterol at W48 (between treatment difference of 12%, 99% power)
NEAT 022
Gatell JM. AIDS 2017;31: ; Gatell JM. Clin Infect Dis 2019 ; 68 :

3. Baseline characteristics and patient disposition
NEAT 022 Study: Switch to DTG vs continuation of PI/r in patients with high cardiovascular risk
Baseline characteristics and patient disposition
DTG
N = 205
PI/r
N = 210
Female, %
11.7
10.0
Age > 50 years, %
87.3
87.6
Framingham score > 10 % at 10 years, %
75.6
71.9
CD4 cell count (/mm3), median
635
585
HIV RNA > 50 c/mL, %
3.4
0.5
HCV serology positive, %
13.4
11.6
Years of HIV RNA < 50 c/mL, median
4.9
5.3
Discontinuation before W48, N (%)
For lack of efficacy
For adverse event
Death
Lost to follow-up
Withdrew consent
Other
14 (6.8) 4 7 1 2
10 (4.8) 3
NEAT 022
Gatell JM. AIDS 2017;31:

4. CV risk factors and ARV therapy at screening
NEAT 022 Study: Switch to DTG vs continuation of PI/r in patients with high cardiovascular risk
CV risk factors and ARV therapy at screening
DTG
N = 205
PI/r
N = 210
Current smoker, % 38
37.8
Diabetes, %
5.5
6.3
Family history of cardiovascular disease, %
43.3
43.4
On lipid lowering agent, %
30.7
28.6
High blood pressure, %
35.3
37.6
Daily exercise, %
32.5
28.9
Fasting total cholesterol, mmol/L, median (IQR)
5.2 ( )
5.1 ( )
Fasting triglycerides, mmol/L, median (IQR)
1.6 ( )
1.6 ( )
NRTI, %
TDF/FTC
ABC/3TC
Other
3.8
PI/r, %
DRV/r
ATV/r
10.7 51
35.2
13.8
NEAT 022
Gatell JM. AIDS 2017;31:

5. Difference (95% CI): - 2.1% (- 6.6 to 2.4)
NEAT 022 Study: Switch to DTG vs continuation of PI/r in patients with high cardiovascular risk
Outcome at W 48, ITT
Treatment success
Discontinuation
for AE
Lost to
follow-up
Other
DTG
PI/r 20 40 60 80
100
93.1
95.2
3.4
2.0
1.0
1.5
1.4
Virologic
non-response
0.5
No virological data %
Difference (95% CI): - 2.1% (- 6.6 to 2.4)
Confirmed virological failure (HIV RNA > 50 c/mL): DTG, N = 4 vs PI/r, N = 1 ; genotype successful in 2/4 and 0/1 patients: no emergence of resistance mutations
NEAT 022
Gatell JM. AIDS 2017;31:

6. Treatment success at W48 (ITT, per-protocol and sub-groups)
NEAT 022 Study: Switch to DTG vs continuation of PI/r in patients with high cardiovascular risk
Treatment success at W48 (ITT, per-protocol and sub-groups)
2.1%
3.0%
2.9%
0.4%
1.1%
6.2%
0.2%
0.1%
- 9
- 6 -3 3 6 9 12
0.44
1.00
95.2
97.5
97.2
92.9
90.1
100
96.9
97.8
93.1
94.5
94.3
92.5
89.0
93.8
96.7
97.7
97.3
53.0
47.0
39.5
23.9
14.9
21.7
ITT analysis
Per-protocol analysis
< 15%
> 15%
United Kingdom
Spain
Germany
Belgium-France-Italy
Framingham 10-years CV risk
Country
PI/r
DTG
% of patients
Difference, % (95 % CI)
p for
interaction
Success (%)
DTG better
PI/r better
NEAT 022
Gatell JM. AIDS 2017;31:

7. Fasting plasma lipids (mmol/L): mean percentage change at W48
NEAT 022 Study: Switch to DTG vs continuation of PI/r in patients with high cardiovascular risk
Fasting plasma lipids (mmol/L): mean percentage change at W48 5 10
- 5
- 10
- 15
- 20
- 25
DTG
PI/r
Total
cholesterol
Non-HDL cholesterol
Triglycerides
LDL cholesterol
HDL cholesterol
Total cholesterol:
HDL-chol. ratio
p < 0.001
p = 0.286
- 8.7
0.7
- 11.3
0.5
-18.4
4.2
- 7.7 2
1.1
2.5
- 7.0
0.4 %
No changes in the utilization of lipid lowering agents (around 30% in each arm, both at baseline and W48)
NEAT 022
Gatell JM. AIDS 2017;31:

8. NEAT 022 Study: Switch to DTG vs continuation of PI/r in patients with high cardiovascular risk
Adverse events, %
DTG + 2 NRTI
N = 205
PI/r + 2 NRTI
N = 210
Grade 3-4 adverse event
5.9
9.1
Serious adverse event
7.7
Adverse event related to treatment
12.8
41 AE in 26 patients
including 15/41 mood, sleep or CNS disorders
7.2
21 AE in 15 patients
including 6/21 mood, sleep or CNS disorders
Discontinuation for adverse event
3.4 (N = 7 *)
1.4 (N = 3 **)
Death
0.5
(N = 1, accidental fall)
* Acute HCV infection (N = 1), mood and/or sleep disorders (N = 6)
** Acute HCV infection (N = 1), dyspepsia (N = 1), worsening of renal function (N = 1)
Median change in eGFR (CKD-EPI) at W48 (p < 0.001)
DTG: ≈ - 8 mL/min
PI/r: 0 mL/min
NEAT 022
Gatell JM. AIDS 2017;31:

9. NEAT 022 Study: Switch to DTG vs continuation of PI/r in patients with high cardiovascular risk
Conclusions
Over 48 weeks, in virologically suppressed patients with high cardiovascular risk (older than 50 years and/or with a Framingham score > 10%) and receiving triple therapy with PI/r + 2 NRTIs
Switching to a DTG regimen was non-inferior. Sensitivity and subgroup analysis support this conclusion
Improved total cholesterol and other lipid fractions in the overall population and in several subgroups
Very few episodes of confirmed virological failure and no resistance mutations selected
Overall tolerance was good and similar in both arms
NEAT 022
Gatell JM. AIDS 2017;31:

10. NEAT 022 Study: Switch to DTG vs continuation of PI/r in patients with high cardiovascular risk87
Outcome at W96, ITT
Treatment success
Adverse event
Lost to follow-up
Other
DTG, immediate switch
DTG, deferred switch 20 40 60 80
100
92.2
87.0
3.9
6.7
2.0
0.5
1.0
1.9
Virologic
non-response
2.4
No virologic data %
Virologic failure
DTG, immediate switch
DTG, deferred switch
Confirmed virologic failure 5
Genotype results available 2 1
Emergence of resistance mutation
NEAT 022
Gatell JM, CID 2018, 14 June (Epub ahead of print)

11. NEAT 022 Study: Switch to DTG vs continuation of PI/r in patients with high cardiovascular risk88
Discontinuation for adverse event W48-W96
Deferred switch, N = 9 (mood and/or sleep disorders, N = 7)
Immediate switch: none
Change in fasting lipids
Deferred switch: improvement of lipid parameters at W96 (total cholesterol, non-HDL cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), all statistically significant and of same level as at W48 in immediate switch group
Immediate switch: stabilisation of improvement between W48 and W96
Change in % of patients receiving or requiring lipid lowering agents according to NCEP ATP-III guidelines
DTG, immediate switch
DTG, deferred switch 30 35 W0 40 45
W48
W96
NEAT 022
Gatell JM. Clin Infect Dis 2019 ; 68 :