Abstract LB-17. ALT / AST, Hemoglobin, Platelets, Serum Creatinine, Viral Load. Prior Treatment Regimen Co-morbid

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1 Failure with All-oral DAA Regimens: Real-world experience from the TRIO Network Nezam Afdhal, Bruce Bacon, Douglas Dieterich, Steven L. Flamm, Lauren Guest, Kris V. Kowdley, Yoori Lee, Naoky Tsai, Zobair Younossi Abstract LB-7 TRIO: Data Elements Collected Patient Demographics Clinical Demographics Treatment Specifications Age Q8K (<5%) Prior Transplant Gender IL-28 Ethnicity Baseline Labs BMI ALT / AST, Hemoglobin, Platelets, Serum Creatinine, Viral Load Co-infection Prior Treatment Status Naïve, Experienced Prior Treatment Response Partial Responder, Responder, Null Responder HIV, HBV Prior Treatment Regimen Co-morbid Current Treatment Regimen Anxiety, Depression, Diabetes Intended Regimen / Duration, Dispensed Regimen / Duration Genotype / Subtype Cirrhosis / Fibrosis Score Drug Dispense Information N, Date, Dose, Days Supplied, Units Treatment Outcomes Discontinuation, EOT, 4, 2

2 TRIO: Patient Disposition Treated with 2 Weeks of Therapy (n=685) (n=52) +RBV (n=76) SMV+SOF+/-RBV (n=4) OBV/PTV/r + DSV +/-RBV (n=47) (n=3) (n=33) (n=9) (n=) (n=) (n=) (n=) (n=4) (n=) (n=) (n=) (n=) (n=432) (n=44) (n=74) (n=) (n=32) (n=5) (n=43) (n=2) TRIO: Baseline Demographics Patients on a 2 week regimen, n = 685 Patient Demographics and Clinical Characteristics at Baseline Group - no. (%) 2 Week + RBV 2 Week SMV + SOF +/- RBV 2 Week OBV/PTV/r + DSV +/- RBV 2 Week n= 52 n= 76 n= 4 n=47 Academic Practice no. (%) 6 (4%) 65 (86%) 23 (56%) 9 (4%) Age - mean (range) 6 (9-89) 59 (4-73) 6 (38-8) 58 (32-8) Male - no. (%) 868 (57%) 56 (74%) 23 (56%) 28 (6%) Patient Ethnicity - no. (%) Asian 53 (3%) (%) (%) (2%) Black 234 (5%) (4%) 5 (2%) 9 (9%) Hispanic/Latin (7%) 5 (7%) 2 (5%) 4 (9%)) Pacific Islander 8 (%) (%) (%) (%) White 742 (49%) 52 (68%) 6 (39%) 23 (49%) Other 2 (%) (%) (%) (%) Unknown 372 (24%) 7 (9%) 8 (44%) (2%) Baseline Labs ALT - mean (s.d.) 69 (59), n=39 82 (53), n=74 66 (79), n=33 83 (8), n=45 AST - mean (s.d.) 62 (45), n= (48), n=74 6 (5), n=32 64 (44), n=45 Hb - mean (s.d.) 4 (7), n=464 4 (2), n=73 4 (), n=34 5 (2), n=45 Platelets < K/ml - no. (%) 42 (%) 5 (2%) 7 (2%) 6 (4%) Platelets >= K/ml - no. (%) 97 (89%) 58 (79%) 27 (79%) 38 (86%) Genotype - no. (%) a 7 (67%) 57 (75%) 28 (68%) 26 (55%) b 433 (28%) 6 (2%) 3 (32%) 2 (45%) Mixed 7 (%) (%) (%) (%) Unknown 64 (4%) 3 (4%) (%) (%)

3 TRIO: 2 Rates by Regimen % 9% 97% 78% 9% 8% 7% 6% 5% 4% 3% 2% % % /52 74/76 32/4 43/47 4 +RBV SMV+SOF+/-RBV VKP+/-RBV +RBV SMV+SOF+/-RBV OBV/PTV/r + DSV TRIO: 2 Rates by Genotype GTa GTb % 9% 96% 79% 88% 96% % 77% 95% 8% 7% 6% 5% 4% 3% 2% % % 95/7 55/57 22/28 23/26 46/433 6/6 /3 2/2 GTa GTb +RBV SMV+SOF+/-RBV OBV/PTV/r + DSV

4 TRIO: 2 Rates by Baseline Viral Load <6MM 6MM+ % 97% 76% 93% % 88% 86% 9% 8% 7% 6% 5% 4% 3% 2% % % 7/84 58/6 25/33 37/4 35/326 26/26 7/8 6/7 <6MMIU/ml 6MM+IU/ml +RBV SMV+SOF+/-RBV OBV/PTV/r + DSV TRIO: 2 Rates by Treatment Status TN TE % 96% 77% 93% 98% 79% 88% 9% 8% 7% 6% 5% 4% 3% 2% % % 893/949 27/28 7/22 28/3 523/556 47/48 5/9 5/7 TN TE +RBV SMV+SOF+/-RBV OBV/PTV/r + DSV

5 TRIO: Predictors of Response All Treatment Regimens n = 685 p=.279 p=.54 p=.949 p=.98 p=.598 p=.249 p=.386 p=.94 p=. age <65 (n=9) age 65+ (n=492) Female (n=7) Male (n=975) Non-African American (n=259) African American (n=9) Academic (n=78) Community (n=967) HIV-Co-infection (n=7) No HIV Co-infection (n=55) Post Transplant (n=46) No Post Transplant (n=588) GTa (n=28) GTb (n=482) <6MM IU/ml (n=37) 6MM+ IU/ml (n=356) Platelet<K/ml (n=7) Platelet K+/ml (n=32) Cirrhosis (n=54) No Cirrhosis (n=38) TE (n=64) TN (n=29) (n=52) +RBV (n=76) SMV+SOF+/-RBV (n=4) OBV/PTV/r + DSV +/-RBV (n=47) 6% 65% 7% 75% 8% 85% 9% 95% % *Closed circles = proportions; whiskers = 95% confidence interval; dotted lines = overall 2; 2-side asympt. p-value via Pearson c2. TRIO: Predictors of Response +/-RBV p=.74 p=.95 p=.923 p=.4 p=.26 p=.834 p=.83 p=.49 n = 52 age <65 (n=62) age 65+ (n=457) Female (n=653) Male (n=868) Non-African American (n=95) African American (n=234) Academic (n=6) Community (n=9) HIV-Co-infection (n=) No HIV Co-infection (n=395) Post Transplant (n=4) No Post Transplant (n=46) GTa (n=7) GTb (n=433) <6MM IU/ml (n=84) 6MM+ IU/ml (n=326) Platelet<K /ml(n=42) Platelet K+ /ml(n=97) age <65 (n=59) age 65+ (n=7) Female (n=2) Male (n=56) Non-African American (n=58) African American (n=) Academic (n=65) Community (n=) Post Transplant (n=3) No Post Transplant (n=42) GTa (n=57) GTb (n=6) <6MM IU/ml (n=6) 6MM+ IU/ml (n=5) Platelet<K/ml (n=5) Platelet K+/ml (n=58) n = 76 97% p=.5 p=.25 p=.823 p=.84 p=.35 p=.749 p=.773 p=.25 +RBV Cirrhosis (n=448) No Cirrhosis (n=35) Cirrhosis (n=3) No Cirrhosis (n=45) p=.225 p=.43 TE (n=556) TN (n=949) TE (n=48) TN (n=28) p=.36 6% 8% % 6% 8% % *HIV excluded due to n<5 in HIV population on +RBV *Closed circles= proportions; whiskers = 95% confidence interval; dotted lines = overall 2; 2-side asympt. p-value via Pearson c2.

6 TRIO: Predictors of Response OBV/PTV/r + DSV +/-RBV p=.76 n =47 9% age <65 (n=38) age 65+ (n=9) p=.35 Female (n=9) Male (n=28) p=.789 Non-African American (n=28) African American (n=9) p=.35 Academic (n=9) Community (n=28) p=.293 GTa (n=26) GTb (n=2) p=.58 <6MM IU/ml (n=4) 6MM+ IU/ml (n=7) p=.27 Platelet<K /ml(n=6) Platelet K+/ml (n=38) p=.56 p=.96 TE (n=7) TN (n=3) p=.397 OBV/PTV/r + DSV (n=9) OBV/PTV/r + DSV +RBV (n=28) 5% 6% 7% 8% 9% % *HIV excluded due to n<5 in HIV population. Post Transplant excluded due to n<5 in Post-Transplant population *Closed circles= proportions; whiskers = 95% confidence interval; dotted lines = overall 2; 2-side asympt. p-value via Pearson c2. Cirrhosis (n=7) No Cirrhosis (n=37) TRIO: Predictors of Response Variable Full Population Distribution % (n) Treatment Failure Distribution % (n) p-value Platelets<k/ml Platelets l+/ml % (7) 89% (32) 4% (9) 6% (29) <. Cirrhosis No Cirrhosis 3% (54) 69% (38) 7% (35) 3% (5) <. Outside FDA Guidelines Inside FDA Guidelines % (49) 9% (536) 33% (7) 37% (34) <. Male Female 58% (975) 42% (7) 76% (39) 24% (2).8 *Patients outside of guidelines: GTa on VKP without RBV, tx failure cirrhotic patients on 2 weeks of VKP+/-RBV, without RBV, or SMV+SOF+/-RBV *2-side asympt. p-value via Pearson c2.

7 TRIO: Conclusions Overall in real world Genotype HCV patients is across all DAA therapies 49 patients were treated outside of FDA guidelines and saw a significantly lower rate (84% outside vs. 95% inside) Platelets <k/ml, cirrhosis, prescribing outside of FDA guidelines, and males all had a positive association with treatment failures Practice type, ethnicity, genotype subtype, baseline viral load, post transplant, age, treatment status, and HIV had no clear association with treatment failures Overall discontinuation rate was <% (2/685)