Jürgen K. Rockstroh, Mark Nelson, Christine Katlama, Jay Lalezari,
Josep Mallolas, Mark Bloch, Gail Matthews, Michael S. Saag,
Philippe Zamor, Chloe Orkin, Jacqueline Gress, Melissa Shaughnessy,
Stephanie Klopfer, Janice Wahl, Bach-Yen Nguyen, Eliav Barr,
Heather L. Platt, Michael Robertson, Mark Sulkowski

• HCV NS3/4A inhibitor, 100 mg • HCV NS5A inhibitor, 50 mg
AIDS 2015
Vancouver, BC
Session:TUAB02
Grazoprevir
(MK-5172)
Elbasvir
(MK-8742)
 Broad genotypic activity 1-3
 Retains activity against many clinically relevant RAVs 1-3
 All-oral, once-daily regimen
1. Summa V, et al. Antimicrobial Agent Chemother 2012:56;4161-67
2. Coburn CA, et al. ChemMedChem 2013; 8: 1930–40
3. Harper S, et al. ACS Med Chem Lett. 2012 Mar 2;3(4):332-6.

AIDS 2015
Vancouver, BC
Session:TUAB02
1-3
– rapid progression of liver disease
– increased risk of cirrhosis, end-stage liver disease, and
HCC 4,5
1. Monga HK, et al. Clin Infect Dis 2001;33(2):240-247. 2. Konerman MA, et al. Hepatology 2014;59(3):767-775
3. Pinchoff J, et al. Clin Infect Dis 2014;58(8):1047-1054. 4. Lo Re V, III, et al. Ann Intern Med 2014;160(6):369-379.
5. Rockstroh JK, et al. J Hepatol 2013;59(2):213-220.

AIDS 2015
Vancouver, BC
Session:TUAB02
n=218 GZR 100 mg / EBR 50 mg Follow-up
D1 TW4 TW8 TW12 FUW4 FUW8 FUW12
• An open-label, single-arm, multicenter study across Europe, The US and
Australia
• Primary endpoint: SVR12 (HCV RNA <15 IU/mL*)
• Treatment-naive patients with HCV GT1, 4 or 6 infection with or without cirrhosis
• Co-infected with HIV-1:
– Naive to ART with CD4+ >500 cells/mm 3 and HIV RNA <50,000 copies/mL
– On stable on ART † for ≥8 weeks and CD4+ >200 cells/mm 3 and undetectable
HIV RNA
*COBAS TaqMan v2.0 [LLoQ <15 IU/mL]
† Stable antiretroviral therapy (ART) included tenofovir or abacavir, and either emtricitabine or lamivudine plus raltegravir, dolutegravir, or rilpivirine

All Patients
N = 218
48.7 (8.9) Age, years mean (SD)
Sex, n (%)
Male,
Female
Race, n (%)
White
Black or African-American
Asian
Other
Ethnicity, n (%)
Hispanic / Latino
Not Hispanic / Latino
Not reported
HCV genotype, n (%)
1a
1b
4
6
Baseline HCV RNA >800,000 IU/mL, n (%)
Cirrhotic*, n (%)
IL28B CC (%) , n (%)
183 (83.9)
35 (16.1)
167 (76.6)
38 (17.4)
6 (2.8)
7 (3.2)
14 (6.4)
194 (89.0)
10 (4.6)
144 (66.1)
44 (20.2)
28 (12.8)
2 (1.0)
130 (59.6)
35 (16.1)
77 (35.3)
*Of the 35 patients (16.1%) with cirrhosis, 27 were diagnosed by Fibroscan, 6 by biopsy, and 2 by Fibrotest and APRI.
AIDS 2015
Vancouver, BC
Session:TUAB02

Antiretroviral therapy, n (%)
Receiving ART with undetectable HIV RNA
Naïve to ART
Baseline CD4 count (cells/µL)
Mean (SD)
Median (1 st quartile – 3 rd quartile)
Antiretroviral therapy, n (%)
Abacavir containing regimen
Tenofovir containing regimen
Raltegravir
Dolutegravir
Rilpivirine
All Patients
N = 218
211 (96.8)
7 (3.2)
613 (0.57)
568 (424-766)
47 (21.6)
164 (75.2)
113 (51.8)
59 (27.1)
38 (17.4)
AIDS 2015
Vancouver, BC
Session:TUAB02

AIDS 2015
Vancouver, BC
Session:TUAB02
100%
Discontinued unrelated to VF
Relapse
Reinfection
75%
50%
25%
0%
96.3%
210
/218*
Full Analysis
Set
1
5
2
210
/217*
96.5%
139
/144
GT1a
0
4
1
*2 patients with GT6 infection were also included; both patients achieved SVR12.
GT = genotype
95.5%
42
/44
GT1b
1
0
1
96.4%
27
/28
GT4
0
1
0

ALL
Gender
Age
Race
IL28B genotype
Cirrhosis
Baseline viral load
Variable
Male
Female
<65 years
≥65 years
White
African American
Asian
CC
Non-CC
No
Yes
≤800,000 IU/mL
>800,000 IU/mL n/m
210/218
175/183
35/35
204/212
6/6
161/167
36/38
6/6
76/77
134/141
175/183
35/35
89/91
121/127
SVR12
% (95% CI)
96.3 (92.9, 98.4)
95.6 (91.6, 98.1)
100.0 (90.0, 100.0)
96.2 (92.7, 98.4)
100.0 (54.1, 100.0)
96.4 (92.3, 98.7)
94.7 (82.3, 99.4)
100 (54.1, 100.0)
98.7 (93.0, 100.0)
95.0 (90.0, 98.0)
95.6 (91.6, 98.1)
100 (90.0, 100.0)
97.8 (92.3, 99.7)
95.3 (90.0, 98.2)
80
AIDS 2015
Vancouver, BC
Session:TUAB02
90
SVR12 (95% CI)
100

Variable
ALL
ART regimen
Abacavir-containing
Tenofovir-containing
ART third agent
Raltegravir
Dolutegravir
Rilpivirine n/m
210/218
44/47
160/164
109/113
59/59
SVR12
% (95% CI)
96.3 (92.9, 98.4)
93.6 (82.5, 98.7)
97.6 (93.9, 99.3)
96.5 (91.2, 99.0)
100.0 (93.9, 100.0)
36/38 94.7 (82.3, 99.4)
AIDS 2015
Vancouver, BC
Session:TUAB02
80 90
SVR12 (95% CI)
100

AIDS 2015
Vancouver, BC
Session:TUAB02
• 5 patients relapsed
– All noncirrhotic
– GT1a n=4; GT4 n=1
– Four patients were receiving ART
• Tenofovir-based ART n=3
• Abacavir-based ART n=1
• 2 patients were reinfected
– One patient with GT1a at enrolment; GT3 at FW12
– One patient with GT1b at enrolment; GT3 at FW12
– Per protocol, these patients was classified as a failure for analysis, but sequencing and phylogenetic data are consistent with post-treatment reinfection

AIDS 2015
Vancouver, BC
Session:TUAB02
RELAPSES
56 yr black/AA male
63 yr black/AA male
37 yr white male
43 yr white male
53 yr white male
REINFECTIONS
35 yr white male
43 yr white male
1a
1a
1a
1a
4
Baseline
HCV GT
1b
1a
ARV regimen
Resistance Associated Variants
At baseline At failure
NS3 NS5A NS3 NS5A tenofovir, emtricitabine, rilpivirine
None tenofovir, emtricitabine, raltegravir abacavir, lamivudine, raltegravir tenofovir, emtricitabine, raltegravir
V36M/L L31M/L Q80K, D168A Q30K, L31M
Q80K Y93S Q80K, D168A Q30R, Y93S
WT WT WT Q30R/Q
WT
WT
WT
WT
WT
WT
WT
L28S abacavir, lamivudine, raltegravir tenofovir, emtricitabine, rilpivirine
WT
V55A/V
WT
WT
(GT3)
(GT3)
(GT3)
(GT3)
Bold indicates RAV detected at virologic failure not previously detected at baseline.

AIDS 2015
Vancouver, BC
Session:TUAB02
At failure
Day 1

AIDS 2015
Vancouver, BC
Session:TUAB02
At failure
Day 1

AIDS 2015
Vancouver, BC
Session:TUAB02
Patients with:
Serious AE, n (%)
Serious drug-related AE, n (%)
Discontinuation due to AE, n (%)
Deaths, n (%)
Any adverse event † , n (%)
Fatigue
Headache
Nausea
Late ALT or AST >5.0 x ULN ‡ , n (%)
Lowest hemoglobin on treatment, n (%)
≥8.5 to <10 g/dL
Elevation of total bilirubin ¶ , n (%)
>2.5 – 5.0 × baseline
>5.0 × baseline
Creatinine >2.5 x baseline, n (%)
All Patients
N = 218
8* (2.8)
0 (0)
0 (0)
0 (0)
167 (76.6)
29 (13.3)
27 (12.4)
20 (9.2)
2 (0.9)
1 (0.5)
8 (3.7)
1 (0.5)
0 (0)
*2 SAEs were reported during the treatment period (convulsion and pneumonia) and 6 SAEs were reported during follow-up (erysipelas; acute psychosis and urinary retention; ulnar fracture; spontaneous bacterial peritonitis, cellulitis, and urinary retention)
†All AEs, regardless of relationship to study drug reported in >5% of patients.
‡ALT/AST >5× ULN after TW4 with an ALT/AST ≤ ULN between TW2 and TW4
¶ Bilirubin elevations were not associated with simultaneous ALT increases

AIDS 2015
Vancouver, BC
Session:TUAB02
• Two patients receiving ART experienced transient HIV viremia during treatment
– Both patients subsequently achieved undetectable HIV RNA with additional compliance education, and without a change in ARV regimen.
• No notable change in CD4 + cells from baseline compared to
TW12
– Mean change of 52.9 cells/µL (SD 156.14, n=207)

AIDS 2015
Vancouver, BC
Session:TUAB02
• High rates of SVR were achieved in patients with HCV GT1,
4 and 6 and HIV co-infection receiving the all-oral, fixed-dose combination of GZR / EBR
– Comparable response rates to other studies in HCV mono-infected patients
– Comparable response rates across all patient subgroups, including black/African American
– Comparable response rates in cirrhotic and non-cirrhotic patients
– Generally well tolerated with few SAEs, and no discontinuation
• Low rates of adverse events, once-daily administration, and suitability for use in patients also receiving antiretroviral therapy suggest GZR / EBR may represent a highly effective treatment option for patients with HCV/HIV co-infection.

AIDS 2015
Vancouver, BC
Session:TUAB02

AIDS 2015
Vancouver, BC
Session:TUAB02
• We extend our gratitude to the patients, their families, investigators and site personnel who participated in this study.
– Australia: Gail Matthews, Mark Theo Bloch
– Canada: Jason Brunetta, Brian Conway
– Denmark: Jan Gerstoft, Nina Weis, Alex Lund Laursen
– France: Marc Bourliere, Christine Katlama, Stanislas Pol
– Germany: Stefan Mauss, Jürgen K. Rockstroh, Michael Sabranski
– Israel: Yaacov Baruch, Oren Shibolet, Ziv Ben Ari
– Spain: Juan Gonzalez Garcia, Josep Mallolas, Christina Tural
– United Kingdom: Mark Nelson, Chloe Orkin
– United States: David Michael Asmuth, Michael David, Laveeza Bhatti, Edwin DeJesus,
Princy N. Kumar, Jacob Paul Lalezari, Kristen Marks, Frederick Nunes, Ponni
Perumalswami, Peter Jerome Ruane, Alyssa So Young Shon, Mark S. Sulkowski, David
Wyles, Philippe J. Zamor, David J Prelutsky, Michael S Saag, Anthony Mills.
• This study and medical writing support by ApotheCom were funded by
Merck & Co., Inc

AIDS 2015
Vancouver, BC
Session:TUAB02
• High rates of SVR were achieved in patients with HCV GT1,
4 and 6 and HIV co-infection receiving the all-oral, fixed-dose combination of GZR / EBR
– Comparable response rates to other studies in HCV mono-infected patients
– Comparable response rates across all patient subgroups, including black/African American
– Comparable response rates in cirrhotic and non-cirrhotic patients
– Generally well tolerated with few SAEs, and no discontinuation
• Low rates of adverse events, once-daily administration, and suitability for use in patients also receiving antiretroviral therapy suggest GZR / EBR may represent a highly effective treatment option for patients with HCV/HIV co-infection.

AIDS 2015
Vancouver, BC
Session:TUAB02

Full Analysis Set: 210/218
• 5 relapses
• 2 reinfections
• 1 discontinuation
Analysis of Sustained Virologic Response
(HCV RNA < LLoQ) at Follow-up Week 12
Visit (SVR
12
) in Treatment-Naïve Subjects
Full Analysis Set
Treatment N n (%) 95%
Confidence
Interval
† p-Value
GZR/EBR for 12 Weeks
†
Based on Clopper-Pearson method.
‡
Based on a one-sided exact test for a binomial proportion. A one-sided p-value<0.025 supports a conclusion that the true SVR
12 is >70%.
‡
N = Number of subjects included in the analysis.
n (%) = Number of subjects who achieved SVR
12 and the percentage calculated as (n/N)*100.
LLoQ is 15 IU/mL.
AIDS 2015
Vancouver, BC
Session:TUAB02

Per Protocol Analysis: 210/217
• 5 relapses
• 2 reinfections
Analysis of Sustained Virologic Response
(HCV RNA < LLoQ) at Follow-up Week 12
Visit (SVR
12
) in Treatment-Naïve Subjects
Per Protocol
Treatment N n (%) 95% Confidence
Interval
†
217 210 (96.8) GZR/EBR for 12 Weeks
†
Based on Clopper-Pearson method.
N = Number of subjects included in the analysis.
n (%) = Number of subjects who achieved SVR
12 and the percentage calculated as
(n/N)*100.
LLoQ is 15 IU/mL.
Data Source: [16.4]
AIDS 2015
Vancouver, BC
Session:TUAB02

BACKUP SLIDES: SUBGROUP ANALYSIS
AIDS 2015
Vancouver, BC
Summary of Sustained Virologic Response (HCV RNA < LLoQ) at Follow-up Week 12
Session:TUAB02
Visit (SVR
12
) by Subgroup
Full Analysis Set
N
Gender
Male
Female
Age
<65
Other
Genotype
1a
1b
1-other
4
6
183
35
>=65
Race
White
African American
Asian
Other
212
6
167
38
6
7
Ethnicity
Hispanic or Latino 14
Not Hispanic or Latino 194
10
144
44
0
28
2
IL28B CC genotype
CC genotype 77
Non-CC genotype 141
Fibrosis Stage
Non-Cirrhotic
Cirrhotic
Baseline HCV RNA
183
35
<=800,000 IU/mL 91
>800,000 IU/mL 127
GZR/EBR for 12 Weeks n (%) 95% Confidence
Interval †
0 (0.0) NA
<=2,000,000 IU/mL 135
>2,000,000 IU/mL 83
<=10,000,000 IU/mL 214
>10,000,000 IU/mL 4
Prior Treatment

BACKUP SLIDES: SUBGROUP ANALYSIS CONTINUED
AIDS 2015
Vancouver, BC
Session:TUAB02
Naïve
Naïve – Interferon Ineligible
Naïve – Interferon Unwilling
Antiretroviral therapy with NRTI backbone
Abacavir containing regimen
‡
Tenofovir containing regimen
Antiretroviral therapy with 3rd agent in
ARV Regimen
Raltegravir
Dolutegravir
Rilpivirine
†
Based on the Clopper-Pearson method.
N
194
11
13
47
164
113
59
38
GZR/EBR for 12 Weeks n (%) 95% Confidence
Interval
†
186 (95.9) (92.0, 98.2)
11 (100.0) (71.5, 100.0)
13 (100.0) (75.3, 100.0)
44 (93.6) (82.5, 98.7)
160 (97.6) (93.9, 99.3)
109 (96.5) (91.2, 99.0)
59 (100.0) (93.9, 100.0)
36 (94.7) (82.3, 99.4)
‡
Includes one subject who was on abacavir, lamivudine, and tenofovir.
N = Number of subjects included in the analysis.
n (%) = Number of subjects who achieved SVR
12 and the percentage calculated as (n/N)*100.
LLoQ is 15 IU/mL.
Data Source: [16.4]

AIDS 2015
Vancouver, BC
Session:TUAB02

AIDS 2015
Vancouver, BC
Session:TUAB02

AIDS 2015
Vancouver, BC
Session:TUAB02