ARV-trials 2017

ARV-trials 2017

Switch to DTG + RPV Switch to DTG + RPV SWORD Study Switch to CAB LA + RPV LA IM LATTE-2 Study SWORD-1 & 2 Studies: Switch to DTG + RPV Design Randomisation 1:1 Open-label 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 W48 W148 N = 513 DTG 50 mg QD + RPV 25 mg QD N = 511 Continuation of cART DTG 50 mg QD + RPV 25 mg QD 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. Lancet. 2018 ; 391:839-49 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 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 29 (5.7%) 17 3

0 5 2 1 1 34 (6.7%) 3 3 3 14 3 7 1 Discontinuation by W52, N (%) Adverse event Lack of efficacy Investigator decision Consent withdrawal Lost to follow-up Protocol deviation Protocol-defined stopping criteria SWORD Llibre JM. Lancet. 2018 ; 391:839-49 SWORD-1 & 2 Studies: Switch to DTG + RPV Virologic outcome at W48 (ITT-E, snapshot) DTG + RPV Continuation cART HIV RNA < 50 c/mL (ITT-E snapshot) SWORD-1 % 100 94.7 Other virologic results at W48 94.9 80 95% DTG + RPV

96% continuation cART Adjusted : - 0.6% (95% CI: - 4.3 to + 3.0) SWORD-2 60 40 94% DTG + RPV 94% continuation cART Adjusted : 0.2% (95% CI: - 3.9 to + 4.2) 20 0 0.6 1.2 Success Virologic HIV RNA < 50 c/mL non-response Difference (95% CI) = - 0.2% (- 3.0 to 2.5) SWORD Confirmed virologic failure: HIV RNA 50 c/mL, retest 200 c/mL No virologic data DTG + RPV, N = 2 4.7 3.9 Emergence of NNRTI resistance mutation (K101K/E) Continued cART, N = 2 No mutations Llibre JM. Lancet. 2018 ; 391:839-49 80

SWORD-1 & 2 Studies: Switch to DTG + RPV 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) ; HIV RNA, c/mL phenotype: sensitive to RPV 10,000,000 1,059,771 1,000,000 100,000 10,000 1,018 1,000 10049 10 49 Screening 49 D1 49 W4 W8 49 W12 49 W24 49 W36 W39

W45 Resuppressed on DTG + RPV SWORD Llibre JM. Lancet. 2018 ; 391:839-49 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 2 <1 Serious adverse event 5 4 4.1 (N = 21 *) N=9 0.6 (N = 3) N=1 Adverse event leading to discontinuation CNS adverse event leading to withdrawal Most common adverse events ( 5% of patients) Nasopharyngitis 10 10 Headache 8 5 Upper respiratory tract infection 5

7 Diarrhea 6 5 Back pain 3 6 * (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), Hodgkins disease (N = 1), Kaposi sarcoma (N = 1), plasmablastic lymphoma (N = 1) SWORD Llibre JM. Lancet. 2018 ; 391:839-49 SWORD-1 & 2 Studies: Switch to DTG + RPV Fasting lipids at baseline and W48 DTG + RPV mg/dL 200 188.1 185.9186 187.6 Continuation cART Baseline Baseline W48 W48 5 4 150 133.1 132.0 121.3 3.8 3.7 3.8 3.7 133.1 3

108.1108.3 107.1 107.3 100 2 52.754.2 53.654.9 50 1 0 0 Total cholesterol SWORD HDL cholesterol LDL cholesterol, calculated Triglycerides Total cholesterol: HDL ratio Llibre JM. Lancet. 2018 ; 391:839-49 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-1infected 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. Lancet. 2018 ; 391:839-49

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