1. PPD Global Feasibility Services
22 March 2013
Switching to Dolutegravir/Abacavir/Lamivudine Fixed Dose Combination (DTG/ABC/3TC FDC) from a PI, INI or NNRTI Based Regimen Maintains HIV Suppression at 48 Weeks
J Lake,1 B Trottier,2 J Garcia-Diaz,3 H Edelstein,4 P Kumar,5 UF Bredeek,6
M Loutfy,7 C Brennan,8 J Koteff,8 B Wynne,9 J Hopking,10 M Aboud11
1University of California, Los Angeles, CA, USA; 2Clinique Médicale l‘Actuel, Montreal, QC, Canada; 3Ochsner Clinic Foundation, New Orleans, LA, USA; 4Highland Hospital, Alameda Health System, Oakland, CA, USA; 5Georgetown University, Washington, DC, USA; 6Metropolis Medical, San Francisco, CA, USA; 7Maple Leaf Research, Toronto, Ontario, Canada; 8ViiV Healthcare, Research Triangle Park, NC, USA; 9ViiV Healthcare, Collegeville, PA, USA; 10GlaxoSmithKline, London, United Kingdom; 11ViiV Healthcare, London, United Kingdom
FS_Slide Deck_Kol Discussion Summary_43792_Millennium _Prostate Cancer_21 March 2013

2. Introduction
DTG/ABC/3TC (Triumeq) is a complete regimen built around DTG, an unboosted INSTI with a high barrier to resistance
First approval of DTG/ABC/3TC: August 2014 in North America
The study enrolled April 2014 to Oct 2014
STRIIVING was conducted to evaluate the efficacy, safety, tolerability, and treatment satisfaction of switching to DTG/ABC/3TC in subjects stable and suppressed on a variety of regimens
T7.7
Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203.

3. STRIIVING Study Design
Countries: US, Canada, Puerto Rico
Open-label,
randomized 1:1
DTG/ABC/3TC
2 NRTIs + PI/r
Current ARTa
DTG/ABC/3TC
Screening
Week 24
Week 48
Primary endpoint at 24 weeks: VL <50 c/mL (Snapshot)
Inclusion criteria
Virologically suppressed (confirmed HIV-1 RNA <50 c/mL)
HLA‑B*5701 negative
Assessments
CD4 cell count changes
Clinical and laboratory safety
Lipids, renal, bone, and cardiovascular changes
Development of resistance
Treatment satisfaction
aStable suppressive current ART with 2 NRTIs plus either a PI, an NNRTI, or an INI. ≥40% PIs, at least 25% INIs.
90% power based on 10% non-inferiority margin (estimated response rate = 85%).
Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203.

4. Study Populations
Subjects randomized to DTG/ABC/3TC on Day 1 who received at least 1 dose of DTG/ABC/3TC → Early-switch
Subjects randomized to continue current ART on Day 1, completed Early Switch Phase at W24, and received at least 1 dose of DTG/ABC/3TC upon switching at Week 24 → Late-switch
Treatment arm
Data included
Early-switch
Day 1 to Week 24
Day 1 to Week 48
Late-switch
Week 24 to Week 48
Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203.

5. Study Disposition: Week 48
Screened
(N=841)
Early Switch group
DTG/ABC/3TC Discontinuations:
Day 1- Week 24
Day 1- Week 48
Adverse event
10 (4%)
Lack of efficacy
(virologic failure)
Protocol deviation
15 (5%)
Stopping criteria met
Lost to follow-up
3 (1%)
8 (3%)
Investigator discretion
5 (2%)
Withdrew consent
4 (1%)
6(2%)
Per sponsor request
1 (<1%)
Randomized and treated
DTG/ABC/3TC
(n=275)
Randomized and treated
cART
(n=278)
Completed Wk 24
(N=239, 87%)
Completed Wk 24
(N=245, 88%)
Late Switch group
DTG/ABC/3TC Discontinuations:
Week 24-48
Adverse event
4 (2%)
Lack of efficacy
(virologic failure)
Protocol deviation
1 (<1%)
Stopping criteria met
Lost to follow-up
3 (1%)
Investigator discretion
Withdrew consent
5 (2%)
Late switch to DTG/ABC/3TC
(N=244)
Completed Wk 48
(N=230, 84%)
Completed Wk 48
(N=230, 94%)
Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203.

6. STRIIVING 48 Week Early Switch Arm Week 24 and 48
DTG/ABC/3TC, Day 1–Week 24 (n=275)a
cART, Day 1–Week 24 (n=278)a
DTG/ABC/3TC, Day 1–Week 48 (n=275)
Switch to DTG/ABC/3TC , Week 24–Week 48 (n=244)b
aITT-E analysis.
Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203.

7. STRIIVING 48 Week Late Switch Arm 24 Weeks Post Switch
Switch to DTG/ABC/3TC , Week 24–Week 48 (n=244)
Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203.

8. Week 24 and 48 Snapshot Outcomes
Early Switch
Late Switch
DTG/ABC/3TC
N=275 n (%)
Day 1 to Wk 24
Day 1 to Wk 48
N=244 n (%)
Wk 24 to Wk 48
Virologic Success
233 (85)
227 (83)
224 (92)
Virologic Non-response
3 (1)
1 (<1)
3 (<1)
Data in window not below threshold
Discontinued while VL not <50*
No Virologic Data
39 (14)
47 (17)
17 (7)
Discontinued due to AE or death
10 (4)
4 (2)
Discontinued for other reasons
25 (9)
32 (12)
7 (3)
Missing data during window but on study
4 (1)
5 (2)
6 (2)
4% of the Early Switch group discontinued treatment due to AEs at Week 24, with none between Weeks 24 and 48; 2% of the Late Switch group discontinued treatment due to AEs between Weeks 24 and 48
*Includes categories: Discontinued for lack of efficacy and Discontinued for other reason while not below threshold
Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203.

9. Virologic Endpoints: DTG/ABC/3TC
No subjects met protocol-defined virologic failure in either study arm
4 subjects >50 at Week 48 window: ES (51), LS (54, 53, 156); All 4 resuppressed < 50 c/mL
Early Switch
Late Switch
DTG/ABC/3TC
N=275
Day 1 to Wk 24
Day 1 to Wk 48
N=244
Wk 24 to Wk 48
PDVFa
Viral load ≥50 c/mL (snapshot)
3 (1%)
1 (<1)
aSubjects with HIV-1 RNA ≥400 c/mL on 2 consecutive assessments any time after randomization are withdrawn = meets protocol defined virologic failure.
Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203.

10. Adverse Events: DTG/ABC/3TC Overall Summary
Early Switch
Late Switch
DTG/ABC/3TC
N=275 n (%)
Day 1 to Wk 24
Day 1 to Wk 48
N=244 n (%)
Wk 24 to Wk 48
Any adverse event, n (%)
180 (65)
206 (75)
146 (60)
Any drug-related event
(occurring ≥2% of subjects in either arm)
57 (21)
60 (22)
32 (13)
Nausea
20 (7)
9 (4)
Diarrhea
9 (3)
3 (1)
Fatigue
Headache
7 (3)
6 (2)
Insomnia
5 (2)
Dizziness
2 (<1)
Abnormal dreams
4 (1)
Any serious eventa
Any fatal eventa
1 (<1)
Discontinuations due to AE or death
10 (4)
4 (2) .
aNone were considered drug-related events.
Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203.

11. Common Adverse Events: DTG/ABC/3TC (≥5% in Any Treatment)
Early Switch
Late Switch
DTG/ABC/3TC
N=275 n (%)
Day 1 to Wk 24
Day 1 to Wk 48
N=244 n (%)
Wk 24 to Wk 48
Nausea
27 (10)
28 (10)
15 (6)
Upper respiratory tract infection
20 (7)
35 (13)
22 (9)
Diarrhea
9 (4)
Fatigue
19 (7)
22 (8)
6 (2)
Headache
13 (5)
17 (6)
10 (4)
Cough
14 (5)
Insomnia
Nasopharyngitis
Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203.

12. Conclusions
Efficacy
The virologic response rate was maintained through 48 weeks in the Early Switch group
In the Late Switch group, virologic suppression was observed in 92% of subjects on DTG/ABC/3TC (24 weeks post-switch)
There were no PDVFs in the study
Tolerability
There were no further discontinuations due to AEs in the Early Switch arm post-Week 24
Low rates of discontinuations in the Late Switch arm (2%)
Summary
Data through 48 weeks support switching to DTG/ABC/3TC once daily for HIV‑1 subjects on stable suppressive cART
Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203.