Wyles D и др. «High SVR rates in HCV/HIV-1 co-infected patients regardless of baseline characteristics» 8th IAS Conference on HIV Pathogenesis, Treatment, and Prevention, Vancouver, 2015. TUAB0203.

1. HIGH SVR RATES IN HCV/HIV-1
CO-INFECTED PATIENTS
REGARDLESS OF BASELINE
CHARACTERISTICS
David Wyles, Joseph J Eron, Jay Lalezari, Chia Wang, Peter J Ruane,
Gary Blick, Laveeza Bhatti, Yiran B Hu, Melannie Co, Krystal Gibbons,
Roger Trinh, Mark S Sulkowski
IAS Conference on HIV Pathogenesis, Treatment and Prevention
• Vancouver, BC, Canada •
21 July 2015

2. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 2
D Wyles: Grant/Research support: AbbVie, BMS, Gilead, Merck, Tacere Therapeutics;
Consultant/Advisor: AbbVie, BMS.
JJ Eron: Grant/Research support: AbbVie, Merck, BMS, GSK/ViiV; Consultant: AbbVie, Gilead, BMS,
GSK/ViiV, Merck, Janssen.
J Lalezari: Research support: AbbVie.
C Wang: Nothing to disclose.
PJ Ruane: Grant/Research support: AbbVie, BMS, Gilead, Merck, Idenix, ViiV, Janssen;
Consultant/Advisor: AbbVie, Merck, Gilead: Speaker: Gilead, ViiV, Merck.
G Blick: Grant/Research support: AbbVie, Gilead Sciences, Sangamo Biosciences, Merck, ViiV;
Consultant/Advisor: BMS, Merck, Serono, ViiV; Speaker: AbbVie, BMS, Merck, Serono, ViiV.
L Bhatti: Consultant/Advisor/Speaker’s Bureau: AbbVie, BMS, Merck, ViiV; Investigator: AbbVie,
Gilead, Janssen, Merck; Advisory Board: Gilead; Stockholder: Gilead
YB Hu, M Co, K Gibbons, and R Trinh: AbbVie employees and may hold AbbVie stock or options.
MS Sulkowski: Consultant/Advisory Board: AbbVie, Achillion, BMS, Gilead, Janssen, Merck; Data
Safety Monitoring Board: Gilead (funds paid to Johns Hopkins University); Study Steering
Committee: Pfizer; Grant/Research support: AbbVie, BMS, Gilead, Merck, Janssen (funds paid to
Johns Hopkins University).
AbbVie sponsored the study (NCT01939197), contributed to its design, participated in the collection, analysis, and interpretation of the data,
and in the writing, reviewing, and approval of this presentation. All authors had access to relevant data.
Disclosures

3. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 3
Co-infection with HCV occurs in 20 – 40% of persons living with HIV
HCV/HIV co-infection is associated with more rapid liver disease
progression, non-hepatic organ dysfunction, and increased overall
mortality compared to HCV mono-infected patients1
In the era of potent HIV ART, liver-related disease is a leading cause of
death in co-infected patients,2,3 thus, guidelines indicate that co-
infected patients should be prioritized for HCV treatment4,5
Recommendations indicate that new interferon-free HCV direct-acting
antiviral (DAA) regimens should be used in co-infected patients as if
they were HCV mono-infected because of similar rates of response4,5
Background
1Lo Re V, et al. Ann Intern Med. 2014;160:369-79. 2Martin-Carbonero L, et al. Clin Infect Dis. 2004;38:128-33.
3Kitahata MM, et al. N Engl J Med. 2009;360:1815-26. 4EASL. J Hepatol. 2015;63:199-236.
5AASLD/IDSA HCV Guidance Panel. Hepatology. 2015:doi: 10.1002/hep.27950.

4. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 4
The 3-DAA (3D) regimen of ombitasvir (OBV), paritaprevir (co-dosed
with ritonavir; PTV/r), and dasabuvir (DSV) with or without ribavirin
(RBV) is approved in 49 countries to treat HCV genotype 1 (GT1)
infection, including those with HIV-1 co-infection
Background
6Sulkowski MS, et al. JAMA. 2015;313(12):1223-31.
In the TURQUOISE-I trial of HCV/HIV-1
co-infected patients with or without
cirrhosis, rates of post-treatment week
12 sustained virologic response (SVR12)
were 94% and 91% receiving 3D + RBV
for 12 or 24 weeks, respectively6
SVR12,%Patients
12-Week 24-Week
0
20
40
60
80
100
9194
29
31
29
32

5. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 5
Examine SVR12 rates by different baseline demographic and disease
characteristics
Objective

6. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 6
Multi-Targeted 3 Direct-Acting Antiviral (3D) Regimen
Ombitasvir
Paritaprevir
/ritonavir
Dasabuvir
Ombitasvir (OBV)
NS5A inhibitor
Paritaprevir (PTV)
NS3/4A protease inhibitor
boosted with ritonavir
PTV was identified by AbbVie and Enanta
Ritonavir does not have antiviral activity against HCV
Dasabuvir (DSV)
a non-nucleoside NS5B RNA
polymerase inhibitor

7. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 7
TURQUOISE-I:
Key Eligibility Criteria
18 to 70 years of age
BMI ≥18 and <38 kg/m2
HCV GT1 infection (plasma HCV RNA >10,000 IU/mL)
HCV treatment-naïve or pegIFN/RBV-experienced
• For pegIFN/RBV-experienced, prior: relapse*, partial response†, or
null response‡
With or without Child-Pugh A cirrhosis
HIV-1 infected
• Plasma HIV-1 RNA <40 copies/mL
• CD4+ count ≥200 cells/mm3 or CD4+% ≥14%
• Stable atazanavir or raltegravir-inclusive ART regimen
*Relapse: HCV RNA undetectable at or after the end of treatment, but with a detectable level within 52 weeks thereafter
† Partial response: >2 log10 IU/mL HCV RNA reduction at treatment week 12 but detectable at end of treatment
‡ Null response: <2 log10 IU/mL or <1 log10IU/mL HCV RNA reduction at treatment week 12 or 4, respectively

8. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 8
TURQUOISE-I:
Baseline Demographics and Disease Characteristics
12-Week Arm
(N = 31)
24-Week Arm
(N = 32)
Male, n (%) 29 (94) 29 (91)
Age ≥55, n (%) 8 (26) 12 (38)
Black race, n (%) 7 (23) 8 (25)
BMI ≥30 kg/m2, n (%) 3 (10) 7 (22)
Fibrosis stage, n (%)
F0-1
F2
F3
F4
16 (52)
5 (16)
4 (13)
6 (19)
20 (63)
5 (16)
1 (3)
6 (19)
IL28B genotype, n (%)
CC
CT
TT
5 (16)
16 (52)
10 (32)
7 (22)
20 (63)
5 (16)
HCV genotype 1a, n (%) 27 (87) 29 (91)
HCV RNA (log10 IU/mL), mean ± SD 6.54 ± 0.57 6.60 ± 0.78

9. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 9
TURQUOISE-I:
Baseline Demographics and Disease Characteristics
12-Week Arm
(N = 31)
24-Week Arm
(N = 32)
Prior pegIFN/RBV experience, n (%)
Naïve 20 (65) 22 (69)
Relapse 1 (3) 3 (9)
Partial response 5 (16) 2 (6)
Null response 5 (16) 5 (16)
History of diabetes, n (%) 0 7 (22)
History of depression/bipolar disorder, n (%) 10 (32) 17 (53)
History of injection drug use, n (%) 8 (26) 13 (41)
CD4+ T-cell count/mm3, mean ± SD
<350, n (%)
350 – <500, n (%)
≥500, n (%)
633 ± 236
2 (7)
8 (26)
21 (68)
625 ± 296
5 (16)
8 (25)
19 (59)
Atazanavir HIV-1 ART regimen, n (%) 16 (52) 12 (38)
Raltegravir HIV-1 ART regimen, n (%) 15 (48) 20 (63)

10. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 10
SVR12,%Patients
12-Week 24-Week
0
20
40
60
80
100
9797
29
30
29
30
TURQUOISE-I:
Modified ITT SVR12 and Analysis Population
To assess factors that may influence
achievement of SVR, non-virologic
failures were removed from the
modified ITT population
• In the 12-week arm, 1 patient
withdrew consent (W10)
• In the 24-week arm, 2 patients had
post-treatment HCV reinfection
Virologic failures included 1 on-
treatment breakthrough at W16
(24-week Arm) and 1 relapse at PTW4
(12-week Arm)

11. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 11
TURQUOISE-I:
SVR12 Rates by Age, Sex, and Race
SVR12,%Patients
0
20
40
60
80
100
94 100100 10088
<55 years 55 years Female Male
100 96 96
22
22
12
12
17
18
27
28
7
8
3
3
26
27
2
2
Age Sex
12-Week 24-Week
96 96 100 100
22
23
22
23
7
7
7
7
Race
Non-Black Black

12. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 12
TURQUOISE-I:
SVR12 Rates by HCV Subtype and Viral Load
SVR12,%Patients
0
20
40
60
80
100
100 96100 10096
1b 1a <800,000 IU/mL 800,000 IU/mL
100 96 96
25
26
26
27
25
26
4
4
4
4
3
3
3
3
26
27
HCV Subtype Baseline Viral Load
12-Week 24-Week

13. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 13
TURQUOISE-I:
SVR12 Rates by IL28B Genotype
SVR12,%Patients
0
20
40
60
80
100
100 100100 100
CC CT TT
89 80
5
5
6
6
8
9
16
16
19
19
4
5
12-Week 24-Week

14. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 14
SVR12,%Patients
0
20
40
60
80
100
100 100100 100
Naïve Relapser Null
Responder
80 80
19
19
4
5
5
5
2
2
4
5
20
20
Partial
Responder
1
1
3
3
100 100
12-Week 24-Week
TURQUOISE-I:
SVR12 Rates by Prior pegIFN/RBV Experience

15. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 15
TURQUOISE-I:
SVR12 Rates by Fibrosis Score
SVR12,%Patients
0
20
40
60
80
100
100 100100 100100
F0-1 F2 F3 F4
100 83 83
16
16
18
18
5
6
3
3
5
5
5
5
1
1
5
6
12-Week 24-Week

16. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 16
SVR12,%Patients
0
20
40
60
80
100
96 10096 100
<30 kg/m2
30 kg/m2
No Yes
10096
26
27
22
23
29
30
3
3
7
7
23
24
6
6
BMI Diabetes History
12-Week 24-Week
0
0
97
TURQUOISE-I:
SVR12 Rates by BMI and History of Diabetes

17. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 17
TURQUOISE-I: SVR12 Rates by
History of IDU and Depression/Bipolar Disorder
IDU, injection drug use
SVR12,%Patients
0
20
40
60
80
100
94 10095 100100
No Yes No Yes
100 90 94
8
8
13
13
21
22
16
17
9
10
15
16
20
20
14
14
IDU Depression/Bipolar
12-Week 24-Week

18. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 18
TURQUOISE-I:
SVR12 Rates by ART Regimen
SVR12,%Patients
0
20
40
60
80
100
100 94100 93
Atazanavir Raltegravir
15
15
12
12
14
15
17
18
12-Week 24-Week

19. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 19
TURQUOISE-I:
SVR12 Rates by CD4+ T-Cell Count
SVR12,%Patients
0
20
40
60
80
100
94 10095 100
500 350 - <500 <350
100 100
19
20
17
18
2
2
8
8
7
7
5
5
12-Week 24-Week

20. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 20
In HCV GT1/HIV-1 co-infected patients, 3D + RBV achieved high rates of
SVR12 regardless of baseline host, viral, and disease characteristics
whether treated with 12 or 24 weeks of therapy
Only 2 of 62 patients had true HCV virologic failure, 1 of whom was not
receiving a label-recommended regimen of 24 weeks for GT1a patients
with cirrhosis
• Both virologic failures were infected with HCV GT1a and had prior
null response to pegIFN/RBV, IL28B TT genotype, and cirrhosis
3D + RBV co-administered with atazanavir or raltegravir ART was well
tolerated with no patient discontinuations due to AEs
Conclusions

21. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 21
Acknowledgements
The authors would like to express their gratitude to the patients and
their families, investigators, and coordinators who made these studies
possible. Medical writing support was provided by Douglas E. Dylla,
PhD, of AbbVie.

23. High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 23
Pt
ID
Tx
Length
Age Sex HCV
GT
BMI Viral
Load
Log10
IU/mL
IL28B
GT
Prior PR
Response
Fibrosis
Stage
ART +
TDF/FTC
HCV
RNA
<LLOQ
(Wk)
CD4
Count
1 12 43 M 1A 27.8 7.69 TT Naïve F3 ATV 2 248
2 12 57 F 1B 27.6 6.03 TT Naïve F2 ATV 1 889
3 12 57 M 1A 24.2 7.08 TT Naïve F0-1 ATV 2 659
4 12 52 M 1A 25.8 7.23 TT Naïve F2 ATV 2 915
5 12 54 M 1B 27.2 6.99 CT Naïve F2 RAL 2 609
6 12 66 M 1A 27.9 6.65 TT Relapser F3 ATV 2 317
7 12 42 M 1A 28.6 5.78 TT Partial F0-1 ATV 1 614
8 24 31 M 1A 26.4 4.90 CT Naïve F3 RAL 1 700
9 24 43 M 1A 28.5 5.75 CT Naïve F0-1 RAL 2 350
10 24 55 M 1A 27.8 7.18 TT Null F4 RAL 2 1234
11 24 38 F 1B 34.3 6.59 CT Naïve F0-1 ATV 1 378
12 24 47 M 1A 26.8 5.57 CT Naïve F0-1 ATV 2 304
13 24 56 F 1A 24.4 6.90 CT Partial F2 RAL 2 413
14 24 51 F 1A 27.3 5.93 CT Relapser F0-1 RAL 2 664
15 24 48 M 1A 29.7 6.48 CT Null F4 ATV 1 906
Demographics of Black/African American Patients