- Background: For the last decade the backbone of hepatitis C (HCV) treatment was the pan-genotyping dual therapy with pegylated interferon alfa in combination with Ribavirin. This regimen was limited in achieving sustained virological response (SVR) and accompanied by serious adverse events. In 2010 there was overwhelming progress in the treatment options for HCV. This change began with the introduction of the first generation specific Direct Antiviral Agents (DAA's) that inhibit the viral protease, agents used in combination with the dual protocol for genotype 1 (triple therapy). In 2014 this revolution continued with the introduction of advanced DAA's targeting different non-structural viral proteins. These DAA's achieve an all oral regimen shorter in duration with outstanding SVR rates and mild side effects. Our liver clinic manages the treatment and follow-up of the vast majority of patients with HCV in southern Israel. As part of the unprecedented advance in the treatment regimen for HCV with the introduction of the first generation DAA's and especially after they were included by the national health care as an option for treatment, we started to treat HCV genotype 1 patients with the triple regimen. Now, in the era of advanced DAA's regimens, we look back, retrospectively, analyze and conclude our experience with a regimen that changed the conception of eradication for HCV by combining immune activation and specific inhibition of functional viral proteins. This was conducted in the hope that it will inspire the development of revolutionary regimens for eradication in other viral diseases. Methods: During the period between September 2011 to November 2013, 55 patients infected with HCV genotype 1 were treated in our outpatient liver clinic with the triple regimen. These patients finished a 6 month period of post-treatment follow-up allowing the evaluation of their viral PCR status at the latest in May 2014. The data were collected from the patient's computerized file and were statistically analyzed by the SMC clinical research center. Results: Out of the 55 patients, 39 received Telaprevir as the protease inhibitor and 16 were treated with Boceprevir. Of all the treated patients 34 achieved SVR; 47% of patients with genotype 1A reached SVR, whereas 71% of those with genotype 1B reached that endpoint. A total of 63.6% of patients with mild or no fibrosis (F 0-2) achieved SVR compared to 63% in patients with advanced fibrosis (F 3-4]. There were 6 patients with no METAVIR evaluation. A total of 57% of naïve patients, 83.3% of prior relapsers and 57.1% of previous non-responders reached SVR at 6 months in current triple therapy. There was no significant response difference in any sub-group when the two first generation PI's were compared. Conclusions: In our experience with first generation PI based triple regiment for HCV genotype 1, though more effective than previous dual treatment, it was still limited in its effectiveness, while creating some major safety issues. In light of this new era where much more effective and safe DAA's emerged and are now in routine use, the triple therapy in our view should be reviewed as a transitional phase that changed forever the concept of eradicating HCV and aimed at specific viral sites. This regimen paved the way for advanced DAA protocols achieving cures in overwhelming unprecedented rates.