High SVR rates in HCV/HIV-1 co-infected patients regardless of baseline characteristics
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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
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Transcript of High SVR rates in HCV/HIV-1 co-infected patients regardless of baseline characteristics
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
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
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.
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
SVR1
2, %
Pati
ents
12-Week 24-Week0
20
40
60
80
1009194
2931
2932
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
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
OmbitasvirParitaprevir/ritonavir
Dasabuvir
Ombitasvir (OBV)NS5A inhibitor
Paritaprevir (PTV)NS3/4A protease inhibitor
boosted with ritonavir
PTV was identified by AbbVie and EnantaRitonavir does not have antiviral activity against HCV
Dasabuvir (DSV)a non-nucleoside NS5B
RNA polymerase inhibitor
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 ageBMI ≥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 cirrhosisHIV-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
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 (%)
F0-1F2F3F4
16 (52)5 (16)4 (13)6 (19)
20 (63)5 (16)1 (3)
6 (19)IL28B genotype, n (%)
CCCTTT
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
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 ± 2362 (7)
8 (26)21 (68)
625 ± 2965 (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)
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 10
SVR1
2, %
Pati
ents
12-Week 24-Week0
20
40
60
80
1009797
2930
2930
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)
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
SVR1
2, %
Pati
ents
0
20
40
60
80
10094 100100 10088
<55 years 55 years Female Male
100 96 96
2222
1212
1718
2728
78
33
2627
22
Age Sex12-Week 24-Week
96 96 100 100
2223
2223
77
77
Race
Non-Black Black
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
SVR1
2, %
Pati
ents
0
20
40
60
80
100100 96100 10096
1b 1a <800,000 IU/mL 800,000 IU/mL
100 96 96
2526
2627
2526
44
44
33
33
2627
HCV Subtype Baseline Viral Load12-Week 24-Week
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
SVR1
2, %
Pati
ents
0
20
40
60
80
100100 100100 100
CC CT TT
89 80
55
66
89
1616
1919
45
12-Week 24-Week
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 14
SVR1
2, %
Pati
ents
0
20
40
60
80
100100 100100 100
Naïve Relapser NullResponder
80 80
1919
45
55
22
45
2020
PartialResponder
11
33
100 100
12-Week 24-Week
TURQUOISE-I:SVR12 Rates by Prior pegIFN/RBV Experience
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
SVR1
2, %
Pati
ents
0
20
40
60
80
100100 100100 100100
F0-1 F2 F3 F4
100 83 83
1616
1818
56
33
55
55
11
56
12-Week 24-Week
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 16
SVR1
2, %
Pati
ents
0
20
40
60
80
10096 10096 100
<30 kg/m2 30 kg/m2 No Yes
10096
2627
2223
2930
33
77
2324
66
BMI Diabetes History12-Week 24-Week
00
97
TURQUOISE-I:SVR12 Rates by BMI and History of Diabetes
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 17
TURQUOISE-I: SVR12 Rates byHistory of IDU and Depression/Bipolar Disorder
IDU, injection drug use
SVR1
2, %
Pati
ents
0
20
40
60
80
10094 10095 100100
No Yes No Yes
100 90 94
88
1313
2122
1617
910
1516
2020
1414
IDU Depression/Bipolar12-Week 24-Week
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
SVR1
2, %
Pati
ents
0
20
40
60
80
100100 94100 93
Atazanavir Raltegravir
1515
1212
1415
1718
12-Week 24-Week
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
SVR1
2, %
Pati
ents
0
20
40
60
80
10094 10095 100
500 350 - <500 <350
100 100
1920
1718
22
88
77
55
12-Week 24-Week
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
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.
High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 2015 23
PtID
TxLength
Age Sex HCV GT
BMI ViralLoadLog10
IU/mL
IL28BGT
Prior PRResponse
FibrosisStage
ART + TDF/FTC
HCV RNA
<LLOQ(Wk)
CD4 Count
1 12 43 M 1A 27.8 7.69 TT Naïve F3 ATV 2 2482 12 57 F 1B 27.6 6.03 TT Naïve F2 ATV 1 8893 12 57 M 1A 24.2 7.08 TT Naïve F0-1 ATV 2 6594 12 52 M 1A 25.8 7.23 TT Naïve F2 ATV 2 9155 12 54 M 1B 27.2 6.99 CT Naïve F2 RAL 2 6096 12 66 M 1A 27.9 6.65 TT Relapser F3 ATV 2 3177 12 42 M 1A 28.6 5.78 TT Partial F0-1 ATV 1 6148 24 31 M 1A 26.4 4.90 CT Naïve F3 RAL 1 7009 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 123411 24 38 F 1B 34.3 6.59 CT Naïve F0-1 ATV 1 37812 24 47 M 1A 26.8 5.57 CT Naïve F0-1 ATV 2 30413 24 56 F 1A 24.4 6.90 CT Partial F2 RAL 2 41314 24 51 F 1A 27.3 5.93 CT Relapser F0-1 RAL 2 66415 24 48 M 1A 29.7 6.48 CT Null F4 ATV 1 906
Demographics of Black/African American Patients
