Background Well-tolerated, highly-effective direct antiviral agents (DAAs) for hepatitis C virus (HCV) were recently introduced. Their utilization has been limited by high cost and low access to care. Aim We aimed to describe the impact of DAAs on HCV treatment and cure rates. Methods We identified all HCV antiviral treatment regimens initiated from 1/1/1999 to 12/31/2015 (n=105,369) in the Veterans Affairs (VA) national healthcare system of the United States and determined if they resulted in sustained virologic response (SVR). Results HCV antiviral treatment rates were low (1,981-6,679 treatments/year) in the interferon era (1999-2010). The introduction of simeprevir and sofosbuvir in 2013 and ledipasvir/sofosbuvir and paritaprevir/ombitasvir/ritonavir/dasabuvir in 2014 were followed by dramatic increases in annual treatment rates to 9,180 in 2014 and 31,028 in 2015. The number of patients achieving SVR was 1,313 in 2010, the last year of the interferon era and increased 5.6-fold to 7,377 in 2014 and 21-fold to 28,084 in 2015. The proportion of treated patients who achieved SVR increased from 19.2% in 1999 and 36.0% in 2010 to 90.5% in 2015. Within 2015, monthly treatment rates ranged from 727 in July to 6,868 in September correlating with the availability of funds for DAAs. Conclusion DAAs resulted in a 21-fold increase in the number of patients achieving HCV cure. Treatment rates in 2015 were limited primarily by the availability of funds. Further increases in funding and cost reductions of DAAs occurring in 2016 suggest that the VA could cure the majority of HCV-infected Veterans in VA care within the next few years.

Background and Aims We aimed to determine whether the HCV viral load after four weeks of treatment (W4VL) with direct-acting antiviral agents (DAAs) predicts sustained virologic response (SVR) in a real-world clinical setting. Methods We identified 21,095 patients who initiated DAA-based antiviral treatment in the national Veterans Affairs (VA) healthcare system from 01/01/2014 to 06/30/2015. W4VL was categorized as undetectable, detectable below quantification (DBQ), detectable above quantification (DAQ) with viral load ≤42 IU/mL (DAQ≤42) and DAQ with viral load > 42 IU/mL (DAQ>42). Results W4VL was undetectable in 36.1%, DBQ in 45.6%, DAQ≤42 in 9.3%, DAQ>42 in 9.1%. DAQ was much more common and undetectable W4VL much less common when tested with the Abbott RealTime HCV assay versus the Roche COBAS AmpliPrep/COBAS TaqMan Version 2 assay. Compared to patients with undetectable W4VL (SVR=93.5%), those with DBQ (SVR=91.8%, adjusted odds ratio [AOR] 0.79, p-value=0.001), DAQ≤42 (SVR=90.0%, AOR 0.63, p-value<0.001) and DAQ>42 (SVR=86.2%, AOR 0.52, p-value<0.001) had progressively lower likelihood of achieving SVR after adjusting for baseline characteristics and treatment duration. Among genotype 1-infected patients who were potentially eligible for 8-week sofosbuvir/ledipasvir monotherapy, we did not find evidence that treatment for 12 weeks instead of 8 weeks was associated with higher SVR, even among those with DAQ. Conclusions DBQ and DAQ W4VL are very common in real-world practice, contrary to what was reported in clinical trials, and strongly predict reduced SVR across genotypes and clinically-relevant patient subgroups. Whether and how W4VL results should influence treatment decisions requires further study.

SUMMARY BackgroundThe effectiveness of anti-viral treatment for hepatitis C virus (HCV) in HIV/HCV co-infected patients in 'real world', clinical practice is unclear.