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The three-direct-acting antiviral (3D) regimen containing ombitasvir, paritaprevir, ritonavir, and dasabuvir with or without ribavirin (RBV) is approved for treatment of hepatitis C virus (HCV) genotype 1 (GT1)/human immunodeficiency virus type 1 (HIV-1) coinfection. Results of a pharmacokinetic substudy of 3D and darunavir are presented. HCV/HIV-1-coinfected subjects were randomized to maintain an antiretroviral regimen with darunavir at 800 mg once daily (QD) or switched to a regimen with darunavir at 600 mg twice daily (BID). On study day 1, subjects received 3D and RBV plus darunavir for 12 weeks. Pharmacokinetic parameters were compared for darunavir and ritonavir with and without 3D (week 4 and day -1). Pharmacokinetic parameters of 3D were compared to historical data. Ten subjects received darunavir QD, and 12 subjects received darunavir BID. The central value ratios (90% confidence interval [CI]) for maximum concentrations (C max ), area under the plasma concentration-time curve between 0 and 24 h postdose (AUC 24 ), and trough plasma concentration at 24 h postdose (C 24 ) of darunavir administered QD with 3D versus administration of darunavir alone were 0.92 (0.72, 1.18), 0.83 (0.71, 0.98), and 0.64 (0.44, 0.93), respectively. The ratios (90% CI) for darunavir C max , AUC 12 , and C 12 administered BID with 3D were 0.92 (0.76, 1.12), 0.88 (0.73, 1.05), and 0.73 (0.58, 0.92), respectively. Exposures of 3D were similar to or slightly lower than those in historical data. All darunavir trough concentrations (C trough ) associated with an HIV-1 RNA level of >40 copies/ml were above the darunavir 50% effective concentration (EC 50 ) of 550 ng/ml for resistant virus. In conclusion, the 3D regimen with darunavir QD or BID did not affect darunavir C max and AUC, whereas the darunavir C trough decreased. Changes in pharmacokinetic parameters of 3D were not considered clinically significant. Episodes of intermittent HIV-1 viremia were infrequent and were not associated with darunavir C trough values below 550 ng/ml. (This study has been registered at ClinicalTrials.gov under identifier NCT01939197.)., (Copyright © 2017 American Society for Microbiology.)

Background & Aims: Patients with chronic hepatitis C virus (HCV) infection and cirrhosis have a higher risk for liver-related complications and have historically been more difficult to cure than patients without cirrhosis. We evaluated the safety and efficacy of ombitasvir/paritaprevir/ritonavir and dasabuvir, without ribavirin, for 12weeks in patients with HCV genotype 1b infection and compensated cirrhosis., Methods: Treatment-naïve and peginterferon/ribavirin treatment-experienced patients received 12weeks of ombitasvir/paritaprevir/ritonavir (25/150/100mg once daily) and dasabuvir (250mgtwicedaily). Key inclusion criteria were hemoglobin ⩾10g/dl, albumin ⩾2.8g/dl, platelet count ⩾25×10(9)/L, creatinine clearance ⩾30ml/min, and Child-Pugh score ⩽6. Efficacy was assessed by the percentage of patients achieving SVR (HCV RNA <25IU/ml) 12weeks post-treatment (SVR12). Efficacy and safety were assessed in all patients receiving study drug., Results: Sixty patients with HCV genotype 1b infection and cirrhosis received treatment. The study population comprised 62% male, 55% treatment-experienced, 83% with IL28B non-CC genotype, 22% with platelet count <90×10(9)/L, and 17% with albumin <3.5g/dl. All 60 patients completed treatment, and SVR12 was achieved in 100% (95% CI, 94.0-100%) of patients. The most common adverse events were fatigue (22%), diarrhea (20%), and headache (18%). Only one patient (1.7%) experienced a serious adverse event. Laboratory abnormalities were infrequently observed and not clinically significant., Conclusions: The HCV regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir without ribavirin for 12weeks achieved 100% SVR12 and was well tolerated in HCV genotype 1b-infected patients with cirrhosis, suggesting that this 12-week ribavirin-free regimen is sufficient in this population., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

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.

Purpose: Women comprise ≯50% of HIV-infected patients, yet safety, tolerability, and efficacy data in women taking antiretrovirals (ARVs) are limited. Lopinavir/ ritonavir (LPV/r)-anchored regimens are globally the most widely prescribed HIV-1 protease inhibitor regimens. The objective was to investigate the safety and efficacy of LPV/r-based therapy in women., Methods: A database query yielded all available data in HIV-1-infected subjects receiving LPV/r-based triple-ARV regimens from randomized clinical trials lasting ≥48 weeks from Abbott or Abbott-supported AIDS Clinical Trials Group studies. Efficacy (HIV-1 RNA levels, CD4+ T-cell counts) and safety and tolerability (treatment discontinuation, treatment-related adverse events [AE], and clinical laboratory abnormalities) at 48 weeks were assessed for total women, women by age (≥50, <50 years) and body mass index (BMI; <25, ≥25 to <30, ≥30 kg/m2), and sex., Results: Nine hundred ninety-two women initiated LPV/r-based therapy (of whom 79.2% were ARV-naïve), with 83.6% completing 48 weeks of treatment. There were 75.5% of women who achieved a threshold of HIV RNA <400 copies/mL by intent-to-treat, non-completer equals failure (ITT, NC = F) analysis, with a mean ± SE CD4+ T-cell count increase of 191.6 ± 4.92 cells/mm3 from baseline. Women aged ≥50 versus <50 years had higher incidence of moderate-to-severe treatment-related AEs and certain laboratory abnormalities, better virologic response (HIV RNA <400 copies/mL by ITT, NC = F), similar immunologic responses, and similar overall incidence of treatment discontinuations. Higher incidences of certain moderate-to-severe treatment-related AEs and laboratory abnormalities occurred in women with BMI ≥30 kg/m2; however, no effect of BMI on efficacy or discontinuation was observed., Conclusions: LPV/r-based regimens were efficacious and well-tolerated in women without marked differences based on age and BMI categories evaluated.

7-11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK [ABSTRACT FROM AUTHOR]