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Despite the availability of highly effective and well-tolerated direct-acting antivirals, not all patients with chronic hepatitis C virus infection receive treatment. This retrospective, multi-centre, noninterventional, case-control study identified patients with chronic hepatitis C virus infection initiating (control) or not initiating (case) treatment at 43 sites in Germany from September 2017 to June 2018. It aimed to compare characteristics of the two patient populations and to identify factors involved in patient/physician decision to initiate/not initiate chronic hepatitis C virus treatment, with a particular focus on historical barriers. Overall, 793 patients were identified: 573 (72%) who received treatment and 220 (28%) who did not. In 42% of patients, the reason for not initiating treatment was patient wish, particularly due to fear of treatment (17%) or adverse events (13%). Other frequently observed reasons for not initiating treatment were in accordance with known historical barriers for physicians to initiate therapy, including perceived or expected lack of compliance (14.5%), high patient age (10.9%), comorbidities (15.0%), alcohol abuse (9.1%), hard drug use (7.7%), and opioid substitution therapy (4.5%). Patient wish against therapy was also a frequently reported reason for not initiating treatment in the postponed (35.2%) and not planned (47.0%) subgroups; of note, known historical factors were also common reasons for postponing treatment. Real-world and clinical trial evidence is accumulating, which suggests that such historical barriers do not negatively impact treatment effectiveness. Improved education is key to facilitate progress towards the World Health Organization target of eliminating viral hepatitis as a major public health threat by 2030., Competing Interests: PB has served as a speaker, a consultant and an advisory board member for AbbVie, Falk, Gilead, Intercept, Merck/MSD, and Norgine, and has received research funding from AbbVie, Falk, Gilead, Intercept, Merck/MSD, and Norgine. HH has served as a speaker and an advisory board member for AbbVie, Gilead, Janssen, MSD, and ViiV Healthcare. SM has served as a speaker and an advisory board member for AbbVie, Gilead, Janssen, and MSD. HG has served as a speaker and a consultant for AbbVie, Gilead, and Sanofi-Aventis; he has served as a speaker and an advisory board member for AbbVie, Gilead, and MSD. DH is an employee of AbbVie Inc and may own stocks and shares in AbbVie Inc. BK is an employee of AbbVie Inc and may own stocks and shares in AbbVie Inc. AGPS is an employee of AbbVie Inc and may own stocks and shares in AbbVie Inc. CN has served as a speaker, a consultant and an advisory board member for AbbVie, Alexion, Biogen, Bristol-Myers Squibb, Falk, Gilead, Janssen, MSD, Sanofi-Genzyme, and Shire-Takeda and has received research funding from AbbVie, Alexion, Biogen, Bristol-Myers Squibb, Falk, Gilead, Janssen, MSD, Sanofi-Genzyme, and Shire-Takeda. TB has served as a speaker and a consultant for AbbVie, Alexion, Bayer, Bristol-Myers Squibb, Eisai, Gilead, Humedics, Intercept, Ipsen, Janssen, Merck/MSD, Novartis, and Sequana Medical, and has received research funding from AbbVie, Alexion, Bayer, Bristol-Myers Squibb, Eisai, Gilead, Humedics, Intercept, Ipsen, Janssen, Merck/MSD, Novartis, and Sequana Medical. AbbVie sponsored the study, and also contributed to its design, and participated in the collection, analysis, and interpretation of the data and in the writing, reviewing, and approval of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Infection with cytomegalovirus (CMV) induces surface expression of major histocompatibility complex (MHC)-class-I-chain-related A (MICA), a ligand for NKG2D. This leads to improved recognition and elimination of infected cells by natural killer (NK) as well as CD8+ T cells. The MICA5.1 allele codes for a truncated protein. This study was performed to test whether impaired expression of a functional MICA protein would influence the susceptibility to severe CMV reactivation in immunocompromised individuals. In this study, the frequency of MICA5.1 was assessed by polymerase chain reaction in 230 Caucasian human immunodeficiency virus (HIV)-1-infected patients and in 219 healthy controls. Patients co-infected with hepatitis C virus (HCV) and GB virus-C served as controls. MICA5.1 allele was analyzed by polymerase chain reaction. Association of MICA5.1 homozygosity and risk of CMV reactivation was calculated by Pearson chi2 test. Comparison of patients with and without a history of CMV disease manifestation revealed that homozygous MICA5.1 genotype was present in a significantly higher frequency in patients with CMV reactivation (33%) than in those without (16%; p 0.032; odds ratio 0.330). The percentage was similar in HIV-1-infected patients and healthy controls. Furthermore, there was no difference in the frequency of MICA5.1 with respect to infection with HCV and GB virus-C. Our study provides the first in vivo demonstration of an association between homozygous MICA5.1 genotype and susceptibility to CMV reactivation in immunocompromised individuals.