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For DAAs with protease inhibitors, potential DDIs should be checked before recommending their use; NS5A protein inhibitors are potent and effective but have a low resistance barrier and variable toxicity profiles, while NS5B polymerase inhibitors have a high genetic barrier, and their metabolism generally does not depend on cytochrome P450 [16]. In general, regimens with the NS5B inhibitor sofosbuvir plus an HCV NS5A inhibitor, which do not affect CYP450, were relatively free of significant pharmacokinetic interactions, even in patients with moderate to severe liver impairment [7]. Actually, recent reviews reported that the administration of drugs concomitantly with SOF generally resulted in fewer DDIs than with protease inhibitor-based regimens [15,16,23]. Currently, the most widely used DAAs demonstrate a moderate DDI risk profile, which is significantly lower compared with first-generation protease inhibitors [24,25]. However, it has been recently shown that despite these advantages, the overall frequency of DDIs in the real-world analysis remained more or less stable over the treatment periods, with about 40% of HCV patients affected [6].
Hepatitis C virus (HCV) infection has long been a major global public health problem; it is not only a leading cause of end-stage liver disease but also results in increased mortality rates for many extrahepatic diseases [1, 2]. In 2015, estimates indicated that approximately 110 million people had a history of HCV infection and 71.1 million people (1% of the global population) were living with active viremic infection [3, 4]. Due to a lack of effective vaccines, patients with HCV must attain a sustained virologic response (SVR) for improved long-term outcomes. SVR is defined as an undetectable serum HCV RNA level 12 weeks posttherapy for patients treated with interferon-free direct-acting antiviral (DAA) therapy or 24 weeks posttherapy for patients treated with interferon-based therapy [5].
As demonstrated in Fig. 1, a total of 62 patients did not complete the treatment protocol with 30 prematurely discontinued treatment and 32 did not complete the post-treatment follow-up. Of these 62 patients, 7 received ribavirin comprising 23.3% of all the 30 patients receiving ribavirin. The percentage of 23.3% non-adherence for the 30 patients with ribavirin use was much higher than that of 6.9% for patients without ribavirin use which consisted 55 non-adherence out of the 793 ribavirin-free patients. Even though, it is difficult to conclude that ribavirin use contributed to the decreased treatment adherence.
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For many years, INDOT stocked and distributed free roadway maps in interstate rest areas and provided them to businesses and citizens as requested. INDOT and the Indiana Destination Development Corp. decided in 2021 to no longer print the annual state roadway map. INDOT distributed remaining maps until the supply was exhausted.
With most travelers now using GPS or smartphone map apps, there is far lower consumer demand for printed roadway maps, but INDOT continues to update the map for our website. The current official INDOT state roadway map is available for download below.
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The American Cancer Society offers programs and services to help you during and after cancer treatment. Below are some of the resources we provide. We can also help you find other free or low-cost resources available. 1e1e36bf2d