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 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 (NCT ), 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 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 patients 1 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 treatment 4,5 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 response 4,5 Background 1 Lo Re V, et al. Ann Intern Med. 2014;160: Martin-Carbonero L, et al. Clin Infect Dis. 2004;38: Kitahata MM, et al. N Engl J Med. 2009;360: EASL. J Hepatol. 2015;63: AASLD/IDSA HCV Guidance Panel. Hepatology. 2015:doi: /hep

High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 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 6 Sulkowski MS, et al. JAMA. 2015;313(12): 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, respectively 6

High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 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 Multi-Targeted 3 Direct-Acting Antiviral (3D) Regimen Ombitasvir Paritaprevir /ritonavir DasabuvirDasabuvir 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

High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July TURQUOISE-I: Key Eligibility Criteria 18 to 70 years of age BMI ≥18 and <38 kg/m 2 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/mm 3 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 10 IU/mL HCV RNA reduction at treatment week 12 but detectable at end of treatment ‡ Null response: <2 log 10 IU/mL or <1 log 10 IU/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 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/m 2, 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 (log 10 IU/mL), mean ± SD6.54 ± ± 0.78

High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July TURQUOISE-I: Baseline Demographics and Disease Characteristics 12-Week Arm (N = 31) 24-Week Arm (N = 32) Prior pegIFN/RBV experience, n (%) Naïve20 (65)22 (69) Relapse1 (3)3 (9) Partial response5 (16)2 (6) Null response5 (16) History of diabetes, n (%)07 (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/mm 3, mean ± SD <350, n (%) 350 – <500, n (%) ≥500, n (%) 633 ± (7) 8 (26) 21 (68) 625 ± (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 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 TURQUOISE-I: SVR12 Rates by Age, Sex, and Race

High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July TURQUOISE-I: SVR12 Rates by HCV Subtype and Viral Load

High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July TURQUOISE-I: SVR12 Rates by IL28B Genotype

High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 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 TURQUOISE-I: SVR12 Rates by Fibrosis Score

High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 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 TURQUOISE-I: SVR12 Rates by History of IDU and Depression/Bipolar Disorder IDU, injection drug use

High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July TURQUOISE-I: SVR12 Rates by ART Regimen

High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July TURQUOISE-I: SVR12 Rates by CD4+ T-Cell Count

High SVR Rates in HCV/HIV-1 Co-Infected Patients Regardless of Baseline Characteristics | IAS 2015 | 21 July 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 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 Pt ID Tx Length AgeSexHCV GT BMIViral Load Log 10 IU/mL IL28B GT Prior PR Response Fibrosis Stage ART + TDF/FTC HCV RNA <LLOQ (Wk) CD4 Count M1A TTNaïveF3ATV F1B TTNaïveF2ATV M1A TTNaïveF0-1ATV M1A TTNaïveF2ATV M1B CTNaïveF2RAL M1A TTRelapserF3ATV M1A TTPartialF0-1ATV M1A CTNaïveF3RAL M1A CTNaïveF0-1RAL M1A TTNullF4RAL F1B CTNaïveF0-1ATV M1A CTNaïveF0-1ATV F1A CTPartialF2RAL F1A CTRelapserF0-1RAL M1A CTNullF4ATV1906 Demographics of Black/African American Patients