Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial.

IMPORTANCE: Patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are at high risk for liver disease progression. However, interferon-based treatments for HCV infection have significant toxicities, limiting treatment uptake. OBJECTIVE: To assess the all-oral 3 direct-acting antiviral (3D) regimen of ombitasvir, paritaprevir (co-dosed with ritonavir [paritaprevir/r]), dasabuvir, and ribavirin in HCV genotype 1-infected adults with HIV-1 co-infection, including patients with cirrhosis. DESIGN, SETTING, AND PARTICIPANTS: TURQUOISE-I is a randomized, open-label study. Part 1a of this pilot study was conducted at 17 sites in the United States and Puerto Rico between September 2013 and August 2014 and included 63 patients with HCV genotype 1 and HIV-1 co-infection who were HCV treatment-naive or had history of prior treatment failure with peginterferon plus ribavirin therapy. The study allowed enrollment of patients, including those with cirrhosis, with a CD4+ count of 200/mm3 or greater or CD4+ percentage of 14% or more and plasma HIV-1 RNA suppressed while taking a stable atazanavir- or raltegravir-inclusive antiretroviral regimen. INTERVENTIONS: Ombitasvir/paritaprevir/r, dasabuvir, and ribavirin for 12 or 24 weeks of treatment as randomized. MAIN OUTCOMES AND MEASURES: The primary assessment was the proportion of patients with sustained virologic response (HCV RNA <25 IU/mL) at posttreatment week 12 (SVR12). RESULTS: Among patients receiving 12 or 24 weeks of 3D and ribavirin, SVR12 was achieved by 29 of 31 (94%; 95% CI, 79%-98%) and 29 of 32 patients (91%; 95% CI, 76%-97%), respectively. Of the 5 patients who did not achieve SVR, 1 withdrew consent, 2 had confirmed virologic relapse or breakthrough, and 2 patients had clinical history and phylogenetic evidence consistent with HCV reinfection. The most common treatment-emergent adverse events were fatigue (48%), insomnia (19%), nausea (18%), and headache (16%). Adverse events were generally mild, with none reported as serious or leading to discontinuation. No patient had a confirmed HIV-1 breakthrough of 200 copies/mL or greater during treatment. CONCLUSIONS AND RELEVANCE: In this open-label, randomized uncontrolled study, treatment with the all-oral, interferon-free 3D-plus-ribavirin regimen resulted in high SVR rates among patients co-infected with HCV genotype 1 and HIV-1 whether treated for 12 or 24 weeks. Further phase 3 studies of this regimen are warranted in patients with co-infection. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01939197.

Safety and efficacy of ombitasvir - 450/r and dasabuvir and ribavirin in HCV/HIV-1 co-infected patients receiving atazanavir or raltegravir ART regimens.

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.