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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.