Baseline HCV RNA and Early Virological Response

SIX WEEKS OF SOFOSBUVIR/LEDIPASVIR (SOF/LDV) ARE SUFFICIENT TO TREAT ACUTE HEPATITIS C VIRUS GENOTYPE 1 MONOINFECTION: THE HEPNET ACUTE HCV IV STUDY K. Deterding, C. Spinner, E. Schott, T. Welzel, G. Gerken, H. Klinker, U. Spengler, J. Wiegand, J. Schulze zur Wiesch, A. Pathil, M. Cornberg, A. Umgelter, C. Zöllner, S. Zeuzem, H. von der Leyen, D. von Witzendorff, M.P. Manns, H. Wedemeyer

Abstract LBO8

Study Design

20 patients with acute HCV G1 with known or suspected exposure to HCV within the preceding four months with documented seroconversion and/or ALT level >10 fold Week 0 6 18

N=20 LDV/SOF FDC SVR12 Baseline Characteristics Study Cohort Patients (n) 20 Male, n (%) 12 (60%) Age (years), Mean (range) 46 (23-63) HCV- Genotype G1a, n (%) 11 (55%) G1b, n (%) 9 (45%) Risk Factors for Infection Sexual transmission, n (%) 11 (55%); including men having sex with men Medical procedures/needle stick injury, n (%) 5 (25%) Nail treatment, n (%) 1 (5%) Unspecified, n (%) 2 (10%) ALT (U/I), Mean (range) 463 (32-2716) Bilirubin (mg/dl, Mean (range) 24 (5.13-111)

Deterding K, et al. 51st EASL; Barcelona, Spain; April 13-17, 2016. Abst. LBO8. Virological Response Acute HCV Study

25 HCV RNA < 15 IU/ml HCV RNA undetectable

Number of Patients (n) 5

0 Week 2 Week 4 Week 6 Follow-up Week 12

Deterding K, et al. 51st EASL; Barcelona, Spain; April 13-17, 2016. Abst. LBO8.

Baseline HCV RNA and Early Virological Response

8.0

7.0

IU/ml) 6.0 10

5.0

4.0

3.0

2.0

1.0 Baseline HCV RNA (log RNA HCV Baseline

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Week 2 HCV RNA Undetectable

Deterding K, et al. 51st EASL; Barcelona, Spain; April 13-17, 2016. Abst. LBO8. Baseline HCV RNA and Early Virological Response

8.0

7.0

IU/ml) 6.0 10

5.0

4.0

3.0

2.0

1.0 Baseline HCV RNA (log RNA HCV Baseline

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Week 2 HCV RNA Undetectable Week 4 HCV RNA <15 IU/ml, Detectable

Deterding K, et al. 51st EASL; Barcelona, Spain; April 13-17, 2016. Abst. LBO8.

ALT Kinetics Over Time

Antiviral Treatment SOF/LDV 3000 Normal ALT n (%) 2500 Baseline 1 (5%) 2000 Week 2 9 (45%) 1500 (ALT), (U/l) (ALT), Week 4 17 (85%) 1000

Alanine Aminotransferase Aminotransferase Alanine Week 6 16 (80%) 500 Follow-up 18 (90%) Week 12 0 ScreeningBaseline Week 2 Week 4 Week 6 Follow-up Week12

Deterding K, et al. 51st EASL; Barcelona, Spain; April 13-17, 2016. Abst. LBO8. Adverse Events 22 Possible/probable Drug-related Adverse Events until Follow-up 12 Gastrointestinal symptoms: 4 patients (20%) Fatigue: 3 patients (15%) Hair loss: 3 patients (15%) Headache: 2 patients (10%) Skin reaction: 2 patients (10%) Abdominal pain: 2 patients (10%) Psychiatric disorders: 2 patients (10%) Other: sleeping disorder, mouth burn, eye disorders, spleen pain

One Serious Adverse Event (SAE) Which was Unrelated to the Study Drug

Deterding K, et al. 51st EASL; Barcelona, Spain; April 13-17, 2016. Abst. LBO8.

Martin: HCV Reinfection Incidence and Outcomes Among HIV-positive MSM in Western Europe

Incident 1st Infection Reinfection Number Included 606 606 Number Reinfected (%) N/A 149 (24.6) Median Time (Years) to Reinfection (IQR) N/A 1.8 (1.1-3.2) G1: 376(70.5) G1: 104(73.2) G2: 13(2.4) G2: 1(0.7) Genotypes (%) G3: 46(8.6) G3: 12(8.5) G4: 96 (18) G4: 25(17.6) Genotype Switches (%) N/A 71/136 (52.2) Median Age at Reinfection (IQR) 39 (34-44) 41 (37-45) Median CD4 at Reinfection 553 (412-760) Proportion with Suppressed HIV VL 91/111 (82.0%) Spontaneously Cleared Proportion 111/605 (18.3%) 21/135 (15.6%)

113 Treated with 87 Achieving SVR (78%)

Martin T, et al. 51st EASL; Barcelona, Spain; April 13-17, 2016. Abst. PS006.