Joseph J Eron1, Jay Lalezari2, Jihad Slim3, Joseph Gathe4, Peter J Ruane5, Chia Wang6, Richard Elion7, Gary Blick8, Amit Khatri9, Yiran B Hu10, Krystal Gibbons11, Linda Fredrick10, Melannie Co12, Ronald D'Amico13, Barbara Da Silva-Tillmann14, Roger Trinh15, Mark S Sulkowski16. 1. Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA. 2. Quest Clinical Research, San Francisco, CA, USA. 3. Infectious Disease Medicine, St. Michael's Medical Center, Newark, NJ, USA. 4. Infectious Disease, Cure C. Consortium, Houston, TX, USA. 5. Peter J. Ruane, MD, Inc., Infectious Disease, Los Angeles, CA, USA. 6. Infectious Diseases, Virginia Mason Medical Center, Seattle, WA, USA. 7. Clinical Medicine, Whitman-Walker Health, Washington, DC, USA. 8. Infectious Diseases, CIRCLE CARE Center, Norwalk, CT, USA. 9. Clinical Pharmacokinetics, AbbVie Inc., North Chicago, IL, USA. 10. Statistics, AbbVie Inc., North Chicago, IL, USA. 11. Clinical Research Management, AbbVie Inc., North Chicago, IL, USA. 12. Medical Review, AbbVie Inc., North Chicago, IL, USA. 13. Medical Affairs, AbbVie Inc., North Chicago, IL, USA. 14. Medical Safety Evaluation, AbbVie Inc., North Chicago, IL, USA. 15. Antiviral Global Project Team, AbbVie Inc., North Chicago, USA. 16. Viral Hepatitis Center, Johns Hopkins University, Baltimore, MD, USA.
Abstract
OBJECTIVE: Whether concomitant HIV antiretroviral therapy (ART) affects the safety and efficacy of interferon-free HCV therapies or whether HCV treatment may negatively affect HIV control is unclear. We assessed the 3 direct-acting antiviral (3D) regimen of ombitasvir, ABT-450 (identified by AbbVie and Enanta; co-dosed with ritonavir) and dasabuvir with ribavirin (RBV) in HCV/HIV-1 co-infected patients with and without cirrhosis, including HCV treatment-experienced, receiving atazanavir (ATV)- or raltegravir (RAL)-based ART therapy. METHODS: HCV genotype 1-positive treatment-naïve or pegIFN/RBV-experienced patients, with or without Child-Pugh A cirrhosis, CD4+ count ≥200 cells/mm(3) or CD4 + % ≥14%, and plasma HIV-1 RNA suppressed on stable ART received open-label 3D + RBV for 12 or 24 weeks. Rates of HCV-sustained virologic response at post-treatment weeks 4 and 12 (SVR4 and SVR12, respectively) and bilirubin-related adverse events (AEs) are reported from post-hoc analyses for subgroups defined by treatment duration and ART regimen. RESULTS: The SVR12 rate for patients receiving 12 weeks of 3D + RBV was 93.5% with comparable rates in patients receiving either ATV (93.8%) or RAL therapy (93.3%) (Table 1). The SVR4 rate for the 24-week arm was 96.9% with a single virologic breakthrough at treatment week 16 in a patient receiving RAL therapy. Patients receiving concomitant ATV had more AEs related to indirect hyperbilirubinemia including ocular icterus, jaundice and grade 3 or 4 elevations in total bilirubin (predominantly indirect). No patient discontinued the study due to AEs, and no serious AEs were reported during or after treatment. No patient had a confirmed plasma HIV-1 RNA value ≥200 copies/mL during the treatment period. CONCLUSIONS: In this first study to evaluate an IFN-free regimen in HCV genotype 1-positive treatment-naïve and experienced patients with HIV-1 co-infection, including those with cirrhosis, high rates of SVR were comparable to those with HCV monoinfection. Indirect hyperbilirubinemia was consistent with the known ABT-450 inhibition of the OATP1B1 bilirubin transporter, RBV-related haemolytic anaemia and inhibitory effect of ATV on bilirubin conjugation. The laboratory abnormalities and AEs observed did not negatively affect treatment response or lead to treatment discontinuation.
OBJECTIVE: Whether concomitant HIV antiretroviral therapy (ART) affects the safety and efficacy of interferon-free HCV therapies or whether HCV treatment may negatively affect HIV control is unclear. We assessed the 3 direct-acting antiviral (3D) regimen of ombitasvir, ABT-450 (identified by AbbVie and Enanta; co-dosed with ritonavir) and dasabuvir with ribavirin (RBV) in HCV/HIV-1 co-infectedpatients with and without cirrhosis, including HCV treatment-experienced, receiving atazanavir (ATV)- or raltegravir (RAL)-based ART therapy. METHODS: HCV genotype 1-positive treatment-naïve or pegIFN/RBV-experienced patients, with or without Child-Pugh A cirrhosis, CD4+ count ≥200 cells/mm(3) or CD4 + % ≥14%, and plasma HIV-1 RNA suppressed on stable ART received open-label 3D + RBV for 12 or 24 weeks. Rates of HCV-sustained virologic response at post-treatment weeks 4 and 12 (SVR4 and SVR12, respectively) and bilirubin-related adverse events (AEs) are reported from post-hoc analyses for subgroups defined by treatment duration and ART regimen. RESULTS: The SVR12 rate for patients receiving 12 weeks of 3D + RBV was 93.5% with comparable rates in patients receiving either ATV (93.8%) or RAL therapy (93.3%) (Table 1). The SVR4 rate for the 24-week arm was 96.9% with a single virologic breakthrough at treatment week 16 in a patient receiving RAL therapy. Patients receiving concomitant ATV had more AEs related to indirect hyperbilirubinemia including ocular icterus, jaundice and grade 3 or 4 elevations in total bilirubin (predominantly indirect). No patient discontinued the study due to AEs, and no serious AEs were reported during or after treatment. No patient had a confirmed plasma HIV-1 RNA value ≥200 copies/mL during the treatment period. CONCLUSIONS: In this first study to evaluate an IFN-free regimen in HCV genotype 1-positive treatment-naïve and experienced patients with HIV-1 co-infection, including those with cirrhosis, high rates of SVR were comparable to those with HCV monoinfection. Indirect hyperbilirubinemia was consistent with the known ABT-450 inhibition of the OATP1B1bilirubin transporter, RBV-related haemolytic anaemia and inhibitory effect of ATV on bilirubin conjugation. The laboratory abnormalities and AEs observed did not negatively affect treatment response or lead to treatment discontinuation.
Authors: Akshanth R Polepally; Haoyu Wang; Patrick J Marroum; Mukul Minocha; Balakrishna Hosmane; Amit Khatri; Sven Mensing; Thomas J Podsadecki; Daniel E Cohen; Walid M Awni; Rajeev M Menon Journal: AAPS J Date: 2017-07-06 Impact factor: 4.009
Authors: Sophia E Schroeder; Peter Higgs; Rebecca Winter; Graham Brown; Alisa Pedrana; Margaret Hellard; Joseph Doyle; Mark Stoové Journal: J Int AIDS Soc Date: 2019-05 Impact factor: 5.396