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
Disclosures
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.
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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Background
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 coinfected 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
1Lo
2Martin-Carbonero L, et al. Clin Infect Dis. 2004;38:128-33.
Re V, et al. Ann Intern Med. 2014;160:369-79.
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.
3Kitahata MM,
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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Background
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
et al. JAMA. 2015;313(12):1223-31.
91
29
31
29
32
12-Week
24-Week
60
40
20
6Sulkowski MS,
94
80
SVR12, % Patients
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
100
0
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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Objective
Examine SVR12 rates by different baseline demographic and disease
characteristics
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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Multi-Targeted 3 Direct-Acting Antiviral (3D) Regimen
Ombitasvir
Paritaprevir
/ritonavir
Ombitasvir (OBV)
NS5A inhibitor
Paritaprevir (PTV)
NS3/4A protease inhibitor
boosted with ritonavir
Dasabuvir
Dasabuvir (DSV)
a non-nucleoside NS5B RNA
polymerase inhibitor
PTV was identified by AbbVie and Enanta
Ritonavir does not have antiviral activity against HCV
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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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 log IU/mL HCV RNA reduction at treatment week 12 but detectable at end of treatment
10
‡ Null response: <2 log IU/mL or <1 log IU/mL HCV RNA reduction at treatment week 12 or 4, respectively
10
10
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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TURQUOISE-I:
Baseline Demographics and Disease Characteristics
Male, n (%)
Age ≥55, n (%)
Black race, n (%)
BMI ≥30 kg/m2, n (%)
Fibrosis stage, n (%)
F0-1
F2
F3
F4
IL28B genotype, n (%)
CC
CT
TT
HCV genotype 1a, n (%)
HCV RNA (log10 IU/mL), mean ± SD
12-Week Arm
(N = 31)
24-Week Arm
(N = 32)
29 (94)
8 (26)
7 (23)
3 (10)
29 (91)
12 (38)
8 (25)
7 (22)
16 (52)
5 (16)
4 (13)
6 (19)
20 (63)
5 (16)
1 (3)
6 (19)
5 (16)
16 (52)
10 (32)
27 (87)
6.54 ± 0.57
7 (22)
20 (63)
5 (16)
29 (91)
6.60 ± 0.78
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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TURQUOISE-I:
Baseline Demographics and Disease Characteristics
Prior pegIFN/RBV experience, n (%)
Naïve
Relapse
Partial response
Null response
History of diabetes, n (%)
History of depression/bipolar disorder, n (%)
History of injection drug use, n (%)
CD4+ T-cell count/mm3, mean ± SD
<350, n (%)
350 – <500, n (%)
≥500, n (%)
Atazanavir HIV-1 ART regimen, n (%)
Raltegravir HIV-1 ART regimen, n (%)
12-Week Arm
(N = 31)
24-Week Arm
(N = 32)
20 (65)
1 (3)
5 (16)
5 (16)
0
10 (32)
8 (26)
633 ± 236
2 (7)
8 (26)
21 (68)
16 (52)
15 (48)
22 (69)
3 (9)
2 (6)
5 (16)
7 (22)
17 (53)
13 (41)
625 ± 296
5 (16)
8 (25)
19 (59)
12 (38)
20 (63)
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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TURQUOISE-I:
Modified ITT SVR12 and Analysis Population
100
97
97
SVR12, % Patients
80
• In the 12-week arm, 1 patient
withdrew consent (W10)
60
• In the 24-week arm, 2 patients had
post-treatment HCV reinfection
40
20
0
To assess factors that may influence
achievement of SVR, non-virologic
failures were removed from the
modified ITT population
29
30
29
30
12-Week
24-Week
Virologic failures included 1 ontreatment breakthrough at W16
(24-week Arm) and 1 relapse at PTW4
(12-week Arm)
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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TURQUOISE-I:
SVR12 Rates by Age, Sex, and Race
100 94
88 100
100 100
22 17
22 18
7
8
<55 years
55 years
96
96
96
96
100 100
100
SVR12, % Patients
80
60
40
20
0
12
12
2
2
3
3
Female
Age
27 26
28 27
22 22
23 23
Male
Non-Black
Sex
12-Week
7
7
7
7
Black
Race
24-Week
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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TURQUOISE-I:
SVR12 Rates by HCV Subtype and Viral Load
100 100
96
96
25
26
26
27
100 100
96
96
25
26
26
27
100
SVR12, % Patients
80
60
40
20
0
4
4
3
3
1b
1a
HCV Subtype
12-Week
4
4
3
3
<800,000 IU/mL 800,000 IU/mL
Baseline Viral Load
24-Week
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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TURQUOISE-I:
SVR12 Rates by IL28B Genotype
100
100
100
100
89
80
5
5
6
6
16
16
19
19
8
9
4
5
100
SVR12, % Patients
80
60
40
20
0
CC
CT
12-Week
TT
24-Week
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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TURQUOISE-I:
SVR12 Rates by Prior pegIFN/RBV Experience
100 100
100 100
100 100
80
80
4
5
4
5
100
SVR12, % Patients
80
60
40
20
0
19
19
20
20
Naïve
1
1
3
3
Relapser
12-Week
5
5
2
2
Partial
Responder
Null
Responder
24-Week
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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TURQUOISE-I:
SVR12 Rates by Fibrosis Score
100 100
100 100
100 100
83
83
5
6
5
6
100
SVR12, % Patients
80
60
40
20
0
16
16
18
18
F0-1
5
5
5
5
F2
12-Week
3
3
1
1
F3
F4
24-Week
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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TURQUOISE-I:
SVR12 Rates by BMI and History of Diabetes
96
96
26
27
22
23
100 100
97
96
29
30
23
24
100
100
SVR12, % Patients
80
60
40
20
0
3
3
<30 kg/m 2
7
7
30 kg/m 2
BMI
No
0
0
6
6
Yes
Diabetes History
12-Week
24-Week
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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TURQUOISE-I: SVR12 Rates by
History of IDU and Depression/Bipolar Disorder
95
94
21
22
16
17
100 100
100 100
90
94
20
20
9
10
15
16
100
SVR12, % Patients
80
60
40
20
0
8
8
No
13
13
Yes
IDU
IDU, injection drug use
14
14
No
Yes
Depression/Bipolar
12-Week
24-Week
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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TURQUOISE-I:
SVR12 Rates by ART Regimen
100
100
93
94
15
15
12
12
14
15
17
18
100
SVR12, % Patients
80
60
40
20
0
Atazanavir
12-Week
Raltegravir
24-Week
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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TURQUOISE-I:
SVR12 Rates by CD4+ T-Cell Count
95
94
100
100
100
100
19
20
17
18
8
8
7
7
2
2
5
5
100
SVR12, % Patients
80
60
40
20
0
500
350 - <500
12-Week
<350
24-Week
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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Conclusions
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
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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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.
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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Demographics of Black/African American Patients
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
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015
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