BackgroundDirect-acting antivirals (DAAs) have revolutionized chronic hepatitis C (HCV) treatment, but real-world effectiveness among vulnerable populations, including uninsured patients, is lacking. This study was conducted to characterize the effectiveness of DAAs in a socioeconomically disadvantaged and underinsured patient cohort.MethodsThis retrospective observational study included all patients undergoing HCV treatment with DAA-based therapy between April 2014 and June 2016 at a large urban safety-net health system (Parkland Health and Hospital System, Dallas, TX, USA). The primary outcome was sustained virologic response (SVR), with secondary outcomes including treatment discontinuation, treatment relapse, and loss to follow-up.ResultsDAA-based therapy was initiated in 512 patients. The cohort was socioeconomically disadvantaged (56% uninsured and 13% Medicaid), with high historic rates of alcohol (41%) and substance (50%) use, and mental health disorders (38%). SVR was achieved in 90% of patients (n = 459); 26 patients (5%) were lost to follow-up. SVR was significantly lower in patients with decompensated cirrhosis (82% SVR; OR 0.37, 95% CI 0.16–0.85) but did not differ by insurance status (P = 0.98) or alcohol/substance use (P = 0.34). Reasons for treatment failure included loss to follow-up (n = 26, 5%), viral relapse (n = 16, 3%), non-treatment-related death (n = 7, 1%), and treatment discontinuation (n = 4, 1%). Of patients with viral relapse, 6 reported non-compliance and have not been retreated, 5 have been retreated and achieved SVR, 4 have undergone resistance testing but not yet initiated retreatment, and 1 was lost to follow-up.ConclusionsEffective outcomes with DAA-based therapy can be achieved in difficult-to-treat underinsured populations followed in resource-constrained safety-net health systems.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0969-3) contains supplementary material, which is available to authorized users.

Voriconazole is the preferred antifungal agent for Aspergillus infections. Therapeutic drug monitoring is recommended to achieve target concentrations and prevent toxicity. However, variable pharmacokinetics, cytochrome P450 polymorphisms, and extensive drug-drug interactions can contribute to subtherapeutic concentrations. We report a voriconazole "boosting" effect of omeprazole to achieve target concentrations for the treatment of Aspergillus in a patient who had persistently subtherapeutic trough concentrations. Voriconazole is a triazole antifungal agent that is the mainstay of therapy for invasive Aspergillus infections (2, 5). Multiple factors, such as age, liver function, and cytochrome P450 (CYP) polymorphisms, affect the systemic exposure of voriconazole (6). Additionally, drug interactions, saturable pharmacokinetics, and significant inter-and intrapatient variability produce unpredictable concentrations. Therapeutic drug monitoring (TDM) is therefore necessary to optimize voriconazole concentrations during the management of invasive fungal infections (IFIs), such aspergillosis. However, the optimal target range remains undefined. Pascual et al. observed a higher response rate for patients with IFIs when trough concentrations were Ͼ1 g/ml (4). A retrospective cohort study found that steady-state concentrations of Ͼ2.05 g/ml were associated with an increased invasive aspergillosis survival rate (10/10 versus 8/18, P Ͻ 0.025) (8). In contrast, voriconazole trough concentrations of Ͼ5.5 g/ml were correlated with toxicity (4).Voriconazole concentrations that fall outside the therapeutic range can occur as a result of drug-drug interactions due to extensive metabolism by CYP enzymes. Voriconazole is a major substrate of CYP2C19, an isoenzyme known for polymorphisms (5). Phenotypic expression of CYP2C19 allelic variants ranges from poor metabolism to ultrarapid metabolism (7). Voriconazole systemic concentrations increase in the presence of CYP2C19 inhibitors. Omeprazole, a widely available proton pump inhibitor, competitively inhibits the CYP2C19 enzyme (3). Wood et al. investigated the effect of omeprazole, given orally at standard doses, on voriconazole pharmacokinetics in 16 patients (11). Omeprazole coadministration increased the mean voriconazole peak concentration in plasma and the area under the curve over the dosing interval by 15 and 41%, respectively. Higher trough concentrations also occurred in the omeprazole-cotreated group. Additionally, other prospective clinical observational data suggest that 44% of patients with supratherapeutic voriconazole concentrations (Ͼ5.5 g/ml) were concomitantly receiving omeprazole (4). Here we report a case of the therapeutic use of omeprazole to "boost" subtherapeutic voriconazole concentrations in a patient with chronic intracranial aspergillosis.In June 2011, a 22-year-old immunocompetent male with a history of intracranial Aspergillus infections was admitted to the Parkland Health and Hospital System (Dallas, TX) after brain magnetic resonance imaging (MRI) s...

Ribavirin is a drug which is essential to produce higher SVR rates both with Peg-IFN and HCV protease inhibitors currently in Phase III clinical trials. Thus, ribavirin is and will remain an important drug to achieving higher SVR rates in HCV infected persons.

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