Background Approximately 3% of the world’s population is infected by the Hepatitis C virus (HCV), and more than 2/3rd of patients have chronic hepatitis. The recent revolutions in HCV treatment have led the World Health Organization to target its elimination as a public health threat by 2030. Objectives To evaluate and compare the efficacy of two therapeutic regimens in HCV management. Patients and Methods This is a comparative prospective clinical study was conducted on 88 patients with HCV at Kurdistan Center for gastroenterology and hepatology (KCGH) in a teaching hospital in the Sulaimaniah City-Kurdistan region of Iraq from January 2020 to December 2020. The patients were divided into two groups; one group received Harvoni (sofosbuvir/ledipasvir), and the other group was given three-drug regimens (Exviera plus Viekrax (ombitasvir/paritaprevir/ritonavir plus dasabuvir) for 12 weeks. The collected data before and after treatment were analyzed through Statistical Package for the Social Sciences (SPSS version 26.0). Results The patients’ mean age was found to be 38.6 years. Males were accounted for a more significant number of the patients (55.7%). The two groups were not significantly different in terms of age, gender, nationality, occupation, BMI, DM, and risk factors (P-value>0.05). But a significant difference was seen between them in terms of their initial glomerular filtration rate (p-value=0.003). In addition, the patients’ gender, age, and HCV genotype were not significantly correlated with their sustain virology response (SVR). Also, a significant difference was observed between the two groups in terms of SVR after three months of treatment, such that more patients who received Harvoni achieved SVR. Moreover, there was a significant relationship between the initial fibrosis stage and the patients’ SVR to the treatment (p-value=0.01). Conclusion Compared to the 3D regimens (Exviera plus Viekrax), Harvoni was more effective for treating patients with chronic HCV.
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