*Purpose: Genotype 4 HCV is the most common genotype in Saudi Arabia and the Middle East. Management of HCV has shifted in the last few years to interferon free regimens with high rates of sustained virological response (SVR12), especially with the use of NS5B/NS5A inhibitor combinations such as sofosbuvir and ledipasvir (Sof-Led). The combination of sofosbuvir and another NS5A inhibitor, daclatasvir (Sof-Dac) has been studied and recommended by the American (AASLD) and the European (EASL) guidelines for the management of HCV genotypes 1-3. However, its use was extended to genotype 4 HCV based on extrapolating evidence in different genotypes. Our hypothesis is that the efficacy of Sof-Dac combination in the treatment of genotype 4 HCV is as good as Sof-Led.

*Methods: A prospective, open-label, 2-period, non-inferiority controlled study for all patients receiving a combination of Sof-Led (Group 1) from Jan 1st, 2014 to Sep 30th, 2016 compared to patients receiving a combination of Sof-Dac (Group 2) starting October 1st, 2016 until March 31st, 2018 at a tertiary care hospital in Riyadh, Saudi Arabia. We included all adult patients ≥ 18 years old with positive HCV PCR, whether they were treatment naive or experienced in pre or post-transplant settings. Patients who are co-infected with human immunodeficiency virus, had previous exposure to an NS5A inhibitor, or with renal impairment (eGFR<30 mL/min/1.73m2) where excluded. The primary endpoint is the proportion of patients achieving SVR12 defined as serum HCV RNA below the lower limit of quantification (LLOQ, 30 IU/mL) 12 weeks after the end of therapy. The secondary endpoint is the change in Child Turcotte Pugh (CTP) scores at week 12 after end of treatment period. The study was designed to recruit 102 subjects from each group. The sample size was determined based on a no inferiority margin of nine percentage points. That is, if the true difference in the 12-week sustained viral response is no more that 9%, the sample size would be sufficient to show a difference.

*Results: Total of 109 patients in group 1 and 111 patients in group 2 were included. For the primary endpoint, 108 (99.08%) patients achieved SVR12 in group 1 versus 106 (95.50%) in group 2 (p= 0.0879). For the secondary end point, the change in CTP score was reported as follow: 98(88.29%) no change, 9 (8.11%) improved and 4 (3.6%) worsened scores in group 1 versus 96(88.07%) patients had no change, 6 (5.50%) improved and 7 (6.42%) worsened scores in group 2 (0.4879).

*Conclusions: This is the largest cohort ever presented that compared generic Sofosbuvir in combination with branded Daclatasvir to Sof-Led in the treatment of genotype 4 HCV infected patients. Our analysis showed that the combination of generic Sofosbuvir with branded Daclatasvir for 12 weeks was non-inferior to the Sof-Led in achieving SVR12.

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