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SWORD-1 & 2 Studies: Switch to DTG + RPV ARV-trial.com SWORD-1 & 2 Studies: Switch to DTG + RPV Design Randomisation 1:1 Open-label W48 W148 HIV+ ≥ 18 years On stable cART ≥ 6 months (2 NRTI + INSTI or PI/r or NNRTI) 1st or 2nd cART with no prior change for virologic failure HIV RNA < 50 c/mL ≥ 12 months HBs Ag negative N = 513 DTG 50 mg QD + RPV 25 mg QD DTG 50 mg QD + RPV 25 mg QD Continuation of cART N = 511 Endpoint Primary: proportion of patients maintaining HIV RNA < 50 c/mL at W48 (ITT-exposed, snapshot) ; non-inferiority if lower margin of a two-sided 95% CI for the difference = - 8% for pooled studies (- 10% for each individual study) SWORD Llibre JM. CROI 2017, Abs. 44LB

SWORD-1 & 2 Studies: Switch to DTG + RPV ARV-trial.com SWORD-1 & 2 Studies: Switch to DTG + RPV Baseline characteristics and patient disposition DTG + RPV N = 513 Continuation cART N = 511 Mean age, years 43 Female, % 23 21 Race: non white, % 18 22 CD4/mm3, median 611 638 Baseline cART, % PI-based NNRTI-based INSTI-based With TDF 26 54 20 73 27 54 19 70 Duration of cART prior to Day 1, median months 51 53 Discontinuation by W52, N (%) Adverse event Lack of efficacy Investigator decision Consent withdrawal Lost to follow-up Protocol deviation Protocol-defined stopping criteria 29 (5.7%) 17 3 5 2 1 34 (6.7%) 14 7 SWORD Llibre JM. CROI 2017, Abs. 44LB

SWORD-1 & 2 Studies: Switch to DTG + RPV ARV-trial.com SWORD-1 & 2 Studies: Switch to DTG + RPV Virologic outcome at W48 (ITT-E, snapshot) Other virologic results at W48 Difference (95% CI) = - 0.2% (- 3.0 to 2.5) 94.7 0.6 4.7 94.9 1.2 3.9 20 40 60 80 100 Success HIV RNA < 50 c/mL Virologic non-response No virologic data % DTG + RPV Continuation cART HIV RNA < 50 c/mL (ITT-E snapshot) SWORD-1 95% DTG + RPV 96% continuation cART Adjusted ≠: - 0.6% (95% CI: - 4.3 to + 3.0) SWORD-2 94% DTG + RPV 94% continuation cART Adjusted ≠: 0.2% (95% CI: - 3.9 to + 4.2) Confirmed virologic failure: HIV RNA ≥ 50 c/mL, retest ≥ 200 c/mL DTG + RPV, N = 2 Emergence of NNRTI resistance mutation (K101K/E) Continued cART, N = 2 No mutations SWORD Llibre JM. CROI 2017, Abs. 44LB

SWORD-1 & 2 Studies: Switch to DTG + RPV ARV-trial.com SWORD-1 & 2 Studies: Switch to DTG + RPV 80 HIV RNA of subject with NNRTI-resistant mutation 41-year-old female Pre-cART HIV RNA > 2 millions c/mL ; 1st cART: TDF/FTC/EFV Randomised to DTG + RPV Documented non-adherence before W36 K101K/E on genotype (fold change RPV = 1.2) ; phenotype: sensitive to RPV HIV RNA, c/mL Screening D1 W4 W8 W12 W24 W36 W39 W45 Resuppressed on DTG + RPV SWORD Llibre JM. CROI 2017, Abs. 44LB

SWORD-1 & 2 Studies: Switch to DTG + RPV ARV-trial.com SWORD-1 & 2 Studies: Switch to DTG + RPV Adverse events, % DTG + RPV N = 513 Continued cART N = 511 Adverse events related to study drug Grade 1-2 Grade 3-4 17 2 < 1 Serious adverse event 5 4 Adverse event leading to discontinuation CNS adverse event leading to withdrawal 4.1 (N = 21 *) N = 9 0.6 (N = 3) N = 1 Most common adverse events (≥ 5% of patients) Nasopharyngitis Headache Upper respiratory tract infection Diarrhea Back pain 10 8 6 3 10 5 7 * (some participants have more than 1 AE) ; anxiety (N = 4), depression (N = 3), insomnia (N = 2), depressed mood (N = 1), headache (N = 1), panic attack (N = 1), suicidal ideation (N = 1), tremor (N = 1), drug-induced liver injury (N = 1), eosinophilic pneumonia, acute (N = 1), abdominal distension (N = 2), dyspepsia (N = 2), peptic ulcer (N = 1), gastrointestinal haemorrhage (N = 1), pancreatitis, acute (N = 1), Hodgkin’s disease (N = 1), Kaposi sarcoma (N = 1), plasmablastic lymphoma (N = 1) SWORD Llibre JM. CROI 2017, Abs. 44LB

SWORD-1 & 2 Studies: Switch to DTG + RPV ARV-trial.com SWORD-1 & 2 Studies: Switch to DTG + RPV Fasting lipids at baseline and W48 Baseline DTG + RPV Continuation cART mg/dL Total cholesterol HDL cholesterol LDL cholesterol, calculated Triglycerides 185.9 50 100 150 200 186 187.6 188.1 52.7 54.2 53.6 54.9 107.1 108.1 108.3 107.3 133.1 121.3 132.0 W48 Total cholesterol: HDL ratio 5 4 3 2 1 3.8 3.7 SWORD Llibre JM. CROI 2017, Abs. 44LB

SWORD-1 & 2 Studies: Switch to DTG + RPV ARV-trial.com SWORD-1 & 2 Studies: Switch to DTG + RPV Conclusion A switch to a novel, once-daily 2 drug-regimen of DTG + RPV demonstrated high efficacy and was non-inferior to the continuation of a combined antiretroviral therapy in virologically suppressed HIV-1–infected adults The safety profiles of both DTG and RPV were consistent with their respective labels Switching to DTG + RPV had a neutral effect on lipids, while significantly improving bone turnover biomarkers  SWORD Llibre JM. CROI 2017, Abs. 44LB