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21st International AIDS Conference; July 18-22, 2016; Durban, South Africa J Lake, 1 B Trottier, 2 J Garcia-Diaz, 3 H Edelstein, 4 P Kumar, 5 UF Bredeek,

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Presentation on theme: "21st International AIDS Conference; July 18-22, 2016; Durban, South Africa J Lake, 1 B Trottier, 2 J Garcia-Diaz, 3 H Edelstein, 4 P Kumar, 5 UF Bredeek,"— Presentation transcript:

1 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa 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 Aboud 11 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 1 University of California, Los Angeles, CA, USA; 2 Clinique Médicale l‘Actuel, Montreal, QC, Canada; 3 Ochsner Clinic Foundation, New Orleans, LA, USA; 4 Highland Hospital, Alameda Health System, Oakland, CA, USA; 5 Georgetown University, Washington, DC, USA; 6 Metropolis Medical, San Francisco, CA, USA; 7 Maple Leaf Research, Toronto, Ontario, Canada; 8 ViiV Healthcare, Research Triangle Park, NC, USA; 9 ViiV Healthcare, Collegeville, PA, USA; 10 GlaxoSmithKline, London, United Kingdom; 11 ViiV Healthcare, London, United Kingdom

2 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa 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 Introduction Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203.

3 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa 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 2 NRTIs + PI/r Open-label, randomized 1:1 DTG/ABC/3TC 0 Week 24 Screening Week 48 Countries: US, Canada, Puerto Rico Current ART a a Stable 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%). Assessments CD4 cell count changes Clinical and laboratory safety Lipids, renal, bone, and cardiovascular changes Development of resistance Treatment satisfaction DTG/ABC/3TC STRIIVING Study Design Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203.

4 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa 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 Study Populations Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. Treatment armData included Early-switch Day 1 to Week 24 Day 1 to Week 48 Late-switchWeek 24 to Week 48

5 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa Study Disposition: Week 48 Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. Randomized and treated DTG/ABC/3TC (n=275) Randomized and treated cART (n=278) Screened (N=841) Completed Wk 48 (N=230, 84%) Late switch to DTG/ABC/3TC (N=244) Completed Wk 48 (N=230, 94%) Early Switch group DTG/ABC/3TC Discontinuations: Day 1- Week 24Day 1- Week 48 Adverse event10 (4%) Lack of efficacy (virologic failure) 00 Protocol deviation15 (5%) Stopping criteria met00 Lost to follow-up3 (1%)8 (3%) Investigator discretion3 (1%)5 (2%) Withdrew consent4 (1%)6(2%) Per sponsor request 1 (<1%)0 Late Switch group DTG/ABC/3TC Discontinuations: Week 24-48 Adverse event4 (2%) Lack of efficacy (virologic failure) 0 Protocol deviation1 (<1%) Stopping criteria met1 (<1%) Lost to follow-up3 (1%) Investigator discretion0 Withdrew consent5 (2%) Completed Wk 24 (N=239, 87%) Completed Wk 24 (N=245, 88%)

6 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa STRIIVING 48 Week Early Switch Arm Week 24 Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. a ITT-E analysis. DTG/ABC/3TC, Day 1–Week 24 (n=275) a Switch to DTG/ABC/3TC, Week 24–Week 48 (n=244) b DTG/ABC/3TC, Day 1–Week 48 (n=275) b cART, Day 1–Week 24 (n=278) a

7 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa STRIIVING 48 Week Early Switch Arm Week 24 and 48 Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. DTG/ABC/3TC, Day 1–Week 24 (n=275) a Switch to DTG/ABC/3TC, Week 24–Week 48 (n=244) b DTG/ABC/3TC, Day 1–Week 48 (n=275) cART, Day 1–Week 24 (n=278) a a ITT-E analysis.

8 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa STRIIVING 48 Week Late Switch Arm 24 Weeks Post Switch Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. Switch to DTG/ABC/3TC, Week 24–Week 48 (n=244)

9 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa 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 Week 24 and 48 Snapshot Outcomes Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. Early Switch DTG/ABC/3TC N=275 n (%) Day 1 to Wk 24 Virologic Success233 (85) Virologic Non-response3 (1) Data in window not below threshold3 (1) Discontinued while VL not <50*0 No Virologic Data39 (14) Discontinued due to AE or death10 (4) Discontinued for other reasons a 25 (9) Missing data during window but on study 4 (1) *Includes categories: Discontinued for lack of efficacy and Discontinued for other reason while not below threshold

10 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa 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 Week 24 and 48 Snapshot Outcomes Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. Early Switch DTG/ABC/3TC N=275 n (%) Day 1 to Wk 24 DTG/ABC/3TC N=275 n (%) Day 1 to Wk 48 Virologic Success233 (85)227 (83) Virologic Non-response3 (1)1 (<1) Data in window not below threshold3 (1)1 (<1) Discontinued while VL not <50*00 No Virologic Data39 (14)47 (17) Discontinued due to AE or death10 (4) Discontinued for other reasons a 25 (9)32 (12) Missing data during window but on study 4 (1)5 (2) *Includes categories: Discontinued for lack of efficacy and Discontinued for other reason while not below threshold

11 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa 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 Week 24 and 48 Snapshot Outcomes Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. Early SwitchLate 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 Virologic Success233 (85)227 (83)224 (92) Virologic Non-response3 (1)1 (<1)3 (<1) Data in window not below threshold3 (1)1 (<1)3 (<1) Discontinued while VL not <50*000 No Virologic Data39 (14)47 (17)17 (7) Discontinued due to AE or death10 (4) 4 (2) Discontinued for other reasons25 (9)32 (12)7 (3) Missing data during window but on study 4 (1)5 (2)6 (2) *Includes categories: Discontinued for lack of efficacy and Discontinued for other reason while not below threshold

12 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa 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 Virologic Endpoints: DTG/ABC/3TC Early SwitchLate 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 PDVF a 000 Viral load ≥50 c/mL (snapshot)3 (1%)1 (<1)3 (1%) Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. a Subjects with HIV-1 RNA ≥400 c/mL on 2 consecutive assessments any time after randomization are withdrawn = meets protocol defined virologic failure.

13 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa Adverse Events: DTG/ABC/3TC Overall Summary Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. Early Switch DTG/ABC/3TC N=275 n (%) Day 1 to Wk 24 Any adverse event, n (%)180 (65) Any drug-related event (occurring ≥2% of subjects in either arm) 57 (21) Nausea20 (7) Diarrhea9 (3) Fatigue9 (3) Headache7 (3) Insomnia5 (2) Dizziness5 (2) Abnormal dreams5 (2) Any serious event a 6 (2) Any fatal event a 1 (<1) Discontinuations due to AE or death10 (4) a None were considered drug-related events.

14 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa Adverse Events: DTG/ABC/3TC Overall Summary Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. Early Switch DTG/ABC/3TC N=275 n (%) Day 1 to Wk 24 DTG/ABC/3TC N=275 n (%) Day 1 to Wk 48 Any adverse event, n (%)180 (65)206 (75) Any drug-related event (occurring ≥2% of subjects in either arm) 57 (21)60 (22) Nausea20 (7) Diarrhea9 (3) Fatigue9 (3) Headache7 (3) Insomnia5 (2) Dizziness5 (2) Abnormal dreams5 (2)4 (1) Any serious event a 6 (2)9 (3) Any fatal event a 1 (<1) Discontinuations due to AE or death10 (4) a None were considered drug-related events.

15 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa Adverse Events: DTG/ABC/3TC Overall Summary Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. Early SwitchLate 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) 57 (21)60 (22)32 (13) Nausea20 (7) 9 (4) Diarrhea9 (3) 3 (1) Fatigue9 (3) 3 (1) Headache7 (3) 6 (2) Insomnia5 (2) 6 (2) Dizziness5 (2) 2 (<1) Abnormal dreams5 (2)4 (1)3 (1) Any serious event a 6 (2)9 (3)6 (2) Any fatal event a 1 (<1) Discontinuations due to AE or death10 (4) 4 (2) a None were considered drug-related events.

16 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa Common Adverse Events: DTG/ABC/3TC (≥5% in Any Treatment) Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. Early Switch DTG/ABC/3TC N=275 n (%) Day 1 to Wk 24 Nausea27 (10) Upper respiratory tract infection20 (7) Diarrhea20 (7) Fatigue19 (7) Headache13 (5) Cough14 (5) Insomnia10 (4) Nasopharyngitis10 (4)

17 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa Common Adverse Events: DTG/ABC/3TC (≥5% in Any Treatment) Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. Early Switch DTG/ABC/3TC N=275 n (%) Day 1 to Wk 24 DTG/ABC/3TC N=275 n (%) Day 1 to Wk 48 Nausea27 (10)28 (10) Upper respiratory tract infection20 (7)35 (13) Diarrhea20 (7) Fatigue19 (7)22 (8) Headache13 (5)17 (6) Cough14 (5)17 (6) Insomnia10 (4)14 (5) Nasopharyngitis10 (4)13 (5)

18 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa Common Adverse Events: DTG/ABC/3TC (≥5% in Any Treatment) Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203. Early SwitchLate 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 Nausea27 (10)28 (10)15 (6) Upper respiratory tract infection20 (7)35 (13)22 (9) Diarrhea20 (7) 9 (4) Fatigue19 (7)22 (8)6 (2) Headache13 (5)17 (6)10 (4) Cough14 (5)17 (6)6 (2) Insomnia10 (4)14 (5)9 (4) Nasopharyngitis10 (4)13 (5)6 (2)

19 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa 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 Conclusions Lake et al. AIDS 2016; Durban, South Africa. Abstract THAB0203.

20 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 CanadaUnited States BarilLeBlancBaxterDretlerHiteMartorellRashbaumShikuma ConwayLogueBensonDube Hoffman- TerryMcDonaldRhameShon de WetLoutfyBhattiEdelsteinHsiaoMeierRichmondSimon FraserRachlisBlickEvans/MartinHuhnMillsRiddellSloan KasperTrottierBolanFeinbergJainMounzerRuaneSmall/Khoury WalmsleyBredeekFelizartaJayaweeraNahass Salazar/ RodriguezStefanic BrennanFifeL. JohnsonNewmanScarsellaVan Dam Puerto RicoBrinsonFlammM. JohnsonNguyenSchneiderVanig MarquezCalvoGallantKinderNovakSchraderWade Melendez- Rivera Chang/P. JohnsonGarcia-DiazKleinOsiyemiScottWard Santiago ColonCunninghamGrossbergKumarParksScribnerWheeler ZorrillaCutroHaginsLakePieroneSha DeJesusHareLalezariPrelutskyShalit DietzHenryLewisRamgopalShamblaw

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