Dolutegravir/Abacavir/Lamivudine Study Results – HIV Suppression Maintenance

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,1B Trottier,2J Garcia-Diaz,3H Edelstein,4P Kumar,5UF Bredeek,6 M Loutfy,7C Brennan,8J Koteff,8B Wynne,9J Hopking,10M Aboud11 1University of California, Los Angeles, CA, USA; 2Clinique M dicale 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 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa

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 Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa

STRIIVING Study Design Countries: US, Canada, Puerto Rico DTG/ABC/3TC Open-label, randomized 1:1 2 NRTIs + PI/r Current ARTa DTG/ABC/3TC Screening 0 Week 48 Week 24 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. 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa

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 Early-switch Early-switch Late-switch Data included Day 1 to Week 24 Day 1 to Week 48 Week 24 to Week 48 Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa

Study Disposition: Week 48 Early Switch group DTG/ABC/3TC Discontinuations: Screened (N=841) Day 1- Week 24 Day 1- Week 48 Adverse event 10 (4%) 10 (4%) Lack of efficacy (virologic failure) 0 0 Randomized and treated cART (n=278) Randomized and treated DTG/ABC/3TC (n=275) Protocol deviation 15 (5%) 15 (5%) Stopping criteria met 0 0 Lost to follow-up 3 (1%) 8 (3%) Investigator discretion 3 (1%) 5 (2%) Withdrew consent 4 (1%) 6(2%) Completed Wk 24 (N=239, 87%) Completed Wk 24 (N=245, 88%) Per sponsor request 1 (<1%) 0 Late Switch group DTG/ABC/3TC Discontinuations: Week 24-48 Late switch to DTG/ABC/3TC (N=244) Adverse event 4 (2%) Lack of efficacy (virologic failure) 0 Protocol deviation 1 (<1%) Completed Wk 48 (N=230, 84%) Completed Wk 48 (N=230, 94%) Stopping criteria met 1 (<1%) Lost to follow-up 3 (1%) Investigator discretion 0 Withdrew consent 5 (2%) Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa

STRIIVING 48 Week Early Switch Arm Week 24 and 48 100 DTG/ABC/3TC, Day 1 Week 24 (n=275)a cART, Day 1 Week 24 (n=278)a 92 88 85 83 DTG/ABC/3TC, Day 1 Week 48 (n=275) Switch to DTG/ABC/3TC , Week 24 Week 48 (n=244)b 80 HIV-1 RNA <50 copies/mL, % 60 40 17 20 14 10 7 1 1 <1 <1 0 Virologic success Virologic non-response No virologic data aITT-E analysis. Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa

STRIIVING 48 Week Late Switch Arm 24 Weeks Post Switch 100 Switch to DTG/ABC/3TC , Week 24 Week 48 (n=244) 92 80 HIV-1 RNA <50 copies/mL, % 60 40 20 7 <1 0 Virologic success Virologic non-response No virologic data Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa

Week 24 and 48 Snapshot Outcomes Early Switch Late Switch DTG/ABC/3TC N=275 n (%) Day 1 to Wk 24 233 (85) 3 (1) 3 (1) 0 39 (14) 10 (4) 25 (9) 4 (1) DTG/ABC/3TC N=275 n (%) Day 1 to Wk 48 227 (83) 1 (<1) 1 (<1) 0 47 (17) 10 (4) 32 (12) 5 (2) DTG/ABC/3TC N=244 n (%) Wk 24 to Wk 48 224 (92) 3 (<1) 3 (<1) 0 17 (7) 4 (2) 7 (3) 6 (2) Virologic Success Virologic Non-response Data in window not below threshold Discontinued while VL not <50* No Virologic Data Discontinued due to AE or death Discontinued for other reasons Missing data during window but on study 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. 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa

Virologic Endpoints: DTG/ABC/3TC No subjects met protocol-defined virologic failure in either study arm Early Switch Late Switch DTG/ABC/3TC N=275 Day 1 to Wk 24 DTG/ABC/3TC N=275 Day 1 to Wk 48 DTG/ABC/3TC N=244 Wk 24 to Wk 48 0 0 0 PDVFa 3 (1%) 1 (<1) 3 (1%) Viral load 50 c/mL (snapshot) 4 subjects >50 at Week 48 window: ES (51), LS (54, 53, 156); All 4 resuppressed < 50 c/mL 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. 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa

Adverse Events: DTG/ABC/3TC Overall Summary Early Switch Late Switch DTG/ABC/3TC N=275 n (%) Day 1 to Wk 24 DTG/ABC/3TC N=275 n (%) Day 1 to Wk 48 DTG/ABC/3TC 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) Nausea Diarrhea Fatigue Headache Insomnia Dizziness Abnormal dreams Any serious eventa 57 (21) 60 (22) 32 (13) 20 (7) 9 (3) 9 (3) 7 (3) 5 (2) 5 (2) 5 (2) 6 (2) 20 (7) 9 (3) 9 (3) 7 (3) 5 (2) 5 (2) 4 (1) 9 (3) 9 (4) 3 (1) 3 (1) 6 (2) 6 (2) 2 (<1) 3 (1) 6 (2) Any fatal eventa 1 (<1) 1 (<1) 1 (<1) Discontinuations due to AE or death 10 (4) 10 (4) 4 (2) aNone were considered drug-related events. Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa

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 DTG/ABC/3TC N=275 n (%) Day 1 to Wk 48 DTG/ABC/3TC 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 20 (7) 20 (7) 9 (4) Fatigue 19 (7) 22 (8) 6 (2) Headache 13 (5) 17 (6) 10 (4) Cough 14 (5) 17 (6) 6 (2) Insomnia 10 (4) 14 (5) 9 (4) Nasopharyngitis 10 (4) 13 (5) 6 (2) Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa

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. 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa

Acknowledgments We thank everyone who has contributed to the success of this study, including All study participants and their families The GlaxoSmithKline and ViiV Healthcare study teams PPD The clinical investigators and their staff Canada United States Baril LeBlanc Baxter Dretler Hite Hoffman- Terry Martorell Rashbaum Shikuma Conway Logue Benson Dube McDonald Rhame Shon de Wet Loutfy Bhatti Edelstein Hsiao Meier Richmond Simon Fraser Kasper Rachlis Trottier Blick Bolan Evans/Martin Feinberg Huhn Jain Mills Mounzer Riddell Ruane Salazar/ Rodriguez Scarsella Schneider Schrader Sloan Small/Khoury Walmsley Bredeek Brennan Brinson Calvo Chang/P. Johnson Felizarta Fife Flamm Gallant Jayaweera L. Johnson M. Johnson Kinder Nahass Newman Nguyen Novak Stefanic Van Dam Vanig Wade Puerto Rico Marquez Melendez- Rivera Garcia-Diaz Klein Osiyemi Scott Ward Santiago Colon Cunningham Grossberg Kumar Parks Scribner Wheeler Zorrilla Cutro Hagins Lake Pierone Sha DeJesus Dietz Hare Henry Lalezari Lewis Prelutsky Ramgopal Shalit Shamblaw 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa