Switch to DTG/ABC/3TC  STRIIVING Study

 Design  Endpoints –Primary: proportion of patients maintaining HIV RNA < 50 c/mL at W48 (ITT-E, snapshot) ; non-inferiority if lower margin of the two-sided 95% CI for the difference = - 10%, 90% power –Secondary: CD4 cell count changes, safety, lipid, renal, bone and cardiovascular changes, development of resistance, treatment satisfaction Switch to DTG/ABC/3TC Continue current ART Randomisation 1 : 1 Open-label HIV RNA < 50 c/mL On 2 NRTI + PI/r or NNRTI or INSTI HLA-B*5701 negative N = 277 N = 274 W24W48 STRIIVING Study: switch to DTG/ABC/3TC Switch to DTG/ABC/3TC STRIIVING Lake J. AIDS 2016, Durban, THAB0203

STRIIVING Study: switch to DTG/ABC/3TC DTG/ABC/3TC N = 274 Continuation of current ART (deferred switch) N = 277 Median age, years4547 Female, %14 Hepatitis B / hepatitis C coinfection, %0 / 80 / 5 Time on ART, median months5551 CD4 cell count (/mm 3 ), median ART at randomisation, % PI4342 NNRTI31 INSTI2627 TDF/FTC backbone7679 Discontinuation, N W0-W24 / W24-W48 For adverse event For protocol deviation For other reasons 36 / 9 10 / 0 15 / 0 11 / 9 32 / 14 0 / 4 17 / 1 15 / 9 Baseline characteristics and patient disposition STRIIVING Lake J. AIDS 2016, Durban, THAB0203

HIV RNA < 50 c/mL (ITT-e) STRIIVING Lake J. AIDS 2016, Durban, THAB0203 * Analysis restricted to patients with deferred switch < < % DTG/ABC/3TC Immediate switch D1-W24 (N = 275) Continuation cART D1-W24 (N = 278) DTG/ABC/3TC Immediate switch D1-W48 (N = 275) DTG/ABC/3TC Deferred switch W24-W48 (N = 244 *)  No subjects met protocol-defined virologic failure in either study arm ; 4 subjects with HIV RNA > 50 c/mL at W48 (1 early switch, 3 deferred switch) ; all 4 resuppressed < 50 c/mL Virologic successVirologic non responseNo virologic data STRIIVING Study: switch to DTG/ABC/3TC

DTG/ABC/3TC (N = 275) Continuation of cART (N = 276) Any adverse event180 (65)124 (45) Adverse event grade 3-48 (3)5 (2) Serious adverse event6 (2)5 (2) Discontinuation for adverse event10 (4)0 Adverse event in ≥ 5% in either group Cough14 (5)8 (3) Diarrhea20 (7)4 (1) Fatigue19 (7)3 (1) Headache13 (5)4 (1) Nausea27 (10)3 (1) Upper respiratory tract infection20 (7) Adverse events at W24, n (%) 111 STRIIVING Trottier B, ICAAC 2015, Session H2 STRIIVING Study: switch to DTG/ABC/3TC

GradeOnset Prior ARV (3 rd drug) 1Insomnia2W1 LPV/r 2Diarrhea, flatulence, rash, Abdominal pain, anxiety, nausea, body ache 1212 W1 RPV 3Euphoric mood, Headache 1212 W1ATV/r 4Abdominal cramps, chills, diarrhea, dizziness, headache2W1 RAL 5Pruritus2W1 NFV 6Upper abdominal pain, diarrhea Fatigue 1, malaise Flu-like syndrome Depression Profuse sweating, change in body odor W1 W9 W12 W17 NVP 7Nasal congestion Worsening fatigue Nausea W2EVG/c 8Alopecia 1W4 ATV/r 9Fatigue 1 1W8 DRV/r 10Homicide 1 NAW10RAL 1 Not drug-related Adverse events leading to discontinuation of DTG/ABC/3TC (N = 10) 112 STRIIVING Study: switch to DTG/ABC/3TC STRIIVING Koteff J. EACS 2015, Abs. LBPS10/1

Total cholesterol HDL - cholesterol LDL- cholesterol Triglycerides Total cholesterol: HDL ratio DTG/ABC/3TC ARTDTG/ABC/3TC ARTDTG/ABC/3TCARTDTG/ABC/3TCARTDTG/ABC/3TCART Change from baseline at W24 (SD) 3.33 (31.88) (25.05) (8.77) (8.43) 4.47 (24.08) 0.93 (21.95) 0.17 (99.59) (76.93) 0.14 (0.88) 0.05 (0.78) Fasting Lipids, mean mg/dL STRIIVING Study: switch to DTG/ABC/3TC STRIIVING Trottier B, ICAAC 2015, Session H2 DTG/ABC/3TC at W24Continuation ART at W24DTG/ABC/3TC at BaselineContinuation ART at Baseline Total cholesterol:HDL ratio Total cholesterolHDLLDLTriglycerides

Mean change from baseline in serum creatinine (mg/dL) through 24 weeks STRIIVING Study: switch to DTG/ABC/3TC STRIIVING Trottier B, ICAAC 2015, Session H2  Small, non-progressive changes in serum creatinine were observed in the DTG/ABC/3TC arm due to known inhibition of tubular creatinine secretion by DTG DTG/ABC/3TC ART Number of patients 84BL1624 Week -0,2 -0,1 0 0,1 0,2 0,3 DTG/ABC/3TCContinuation ART

Treatment Satisfaction (HIVTSQ) Adjusted mean change in total score at W24 STRIIVING Study: switch to DTG/ABC/3TC STRIIVING Trottier B, ICAAC 2015, Session H2  At baseline, overall treatment satisfaction scores were similar between groups Adjusted mean difference at W24 (95% CI): 2.4 (1.3, 3.5) ; p < DTG/ABC/3TCContinuation ART DTG/ABC/3TC (N = 269)ART (N = 276)

STRIIVING Study: switch to DTG/ABC/3TC  Conclusion –Efficacy Similar virologic response for DTG/ABC/3TC and continuation of current ART at W24, with non-inferiority Success 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 protocol-defined virologic failure in the study –Tolerability 4% of subjects discontinued due to adverse events by W24 in the DTG/ABC/3TC arm vs 0% in the continuation group There were no further discontinuations due to adverse events in the early switch arm post-week 24 Rates of discontinuation for adverse events in the late switch arm was 2% 113 STRIIVING Lake J. AIDS 2016, Durban, THAB0203