Review Looks at Success of New Anti-Virals in HCV Treatment

By Annette M. Boyle

Transformation of hepatitis C antiviral treatment in a national healthcare system following the introduction of direct antiviral agents

SEATTLE — Over the next year or so, the remarkable transformation of hepatitis C (HCV) treatment at the VA will likely reach some type of equilibrium, a new study suggested.

The introduction of highly effective antiviral agents began to revolutionize care in 2014, reaching an astounding cure rate of 90.5% among those receiving the new therapies, according to a recent analysis published in the journal Alimentary Pharmacology and Therapeutics.1

Senior author George Ioannou, MD, MS, of the VA Puget Sound Healthcare System and University of Washington, both in Seattle, predicted that, by the end of 2018, the VA will have treated the majority of HCV-infected patients who would stand to benefit from treatment.

“However, there will continue to be new infections occurring, or new patients seeking care within the VA in order to get antiviral treatment,” Ioannou told U.S. Medicine. “There is also a small proportion of HCV-infected patients who have very limited life expectancy due to other comorbidities (e.g. terminal cancers) who decide in consultation with their physicians not to undergo antiviral treatment.”

He and his co-authors pointed out that, in an analysis of 107,079 HCV antiviral treatment regimens initiated in the VHA from 1999 through 2015, cure rates shot up from 19.2% in 1999 to 36% in 2010 before the almost miraculous increase to 90.5% in 2015.

The study noted that the number of patients achieving sustained virologic response was 1,313 in 2010, the last year of the interferon era, and then more than quintupled to 7,377 in 2014 before burgeoning 21-fold to 28,084 in 2015.

“The introduction of effective direct antiviral agents together with the allocation of appropriate funds and resources allowed the VA healthcare system to treat and cure hepatitis C in unprecedented numbers,” Ioannou said. “In fact, out of approximately 57,500 patients cured of hepatitis C in the VA since 1999, approximately half were cured in a single year in 2015. The question is whether we are delivering these medications to the patients who need them and what obstacles there are to treating and curing the majority of hepatitis C infected patients.”

Another study, published late last year in the journal Gastroenterology, looked at the effectiveness of sofosbuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) in treatment of different subgroups of patients infected with hepatitis C virus (HCV) genotypes 1, 2, 3 or 4.2


Led by Ioannou, researchers conducted a retrospective analysis of data from 17,487 patients with HCV infection—13,974 with HCV genotype 1; 2131 with genotype 2; 1237 with genotype 3; and 135 with genotype 4)—who were treated between Jan.1, 2014 through June 20, 2015. Results indicated that, after eight to 24 weeks of therapy, 75% to 93% had no detectable levels of the disease in their blood for 12 or more weeks after the end of treatment.


“This promising news comes as VA is dedicating significant funds to help greater numbers of patients with hepatitis C,” VA Secretary David Shulkin, then-VA under secretary for health, said when the results were released late last year. “In March, we announced our ability to fund care for all veterans with hepatitis C for fiscal year 2016, regardless of the stage of the patient’s liver disease. VA has long led the country in screening for and treating hepatitis C. As of mid-September 2016 alone, the department treated more than 100,000 veterans infected with the virus. More than 68,000 of these patients had been treated with these new highly effective antivirals.”

Cost of Treatment

While cost of the treatment has been a constant concern, reduced drug prices and increased funding are now enabling the VA to offer treatment for all veterans infected with the disease, regardless of their level of liver damage.

“The VA is constantly negotiating contracts with the major manufacturers of hepatitis C direct-acting antiviral agents and, consequently, the prices are changing and usually dropping over time. In general, the VA is able to negotiate some of the least expensive prices for antiviral agents,” Ioannou explained. “In fiscal year 2015, the VA allocated approximately $750 million towards the medication costs of DAAs. This increased to $1.5 billion in fiscal year 2016 and again $1.5 billion in fiscal year 2017. It is obviously uncertain yet what the budget will be for fiscal year 2018.”

The VA healthcare system is the largest provider of care for chronic HCV infection in the United States, with more than 174,302 patients with diagnosed HCV infection in VA care as of 2013 and an additional estimated 45,000 patients with undiagnosed HCV. Until the last few years, effective treatment was limited for many of those veterans.

That was especially the case for the HCV patients reviewed in the most recent study. The report stated that, among those veterans who averaged 56.2 years old and were 61.7% white, 21.5% had cirrhosis, 6.6% had decompensated cirrhosis and 1.7% had hepatocellular carcinoma.


Background information in the article noted that, until recently, many payers and healthy systems outside of the VA denied or limited treatment with DAAs for patients with advanced liver fibrosis, cirrhosis or extrahepatic manifestations of HCV because of the high costs.

The article suggested that critics of nearly-universal treatment might have been misguided.


“The current DAA regimens have a success rate well above 90%, which means that the vast majority of patients will get cured and will require only one treatment,” Ioannou said. “However, the interferon-based regimens that were used in the past had a success rate below 50%, hence many patients required multiple treatments. In particular, there are many patients in the study who failed an interferon-based treatment and were then treated successfully with DAAs.”

The study concluded on an optimistic note, stating, “The acceleration in treatment provision, particularly in August and September 2015, demonstrates the abilities of the VA’s existing HCV treatment infrastructure when sufficient funding for DAAs is available. These results raise the specter of near-complete eradication of HCV within the VA system, which given the 124 662 VA patients with diagnosed HCV, would substantially reduce the burden of HCV within the entire country and prevent tens of thousands of deaths.”

Ioannou added that there still is a way to go, pointing out, “The number of patients treated in 2016 increased again to 37,025, as we had predicted in our article. It is inevitable of course that at some point the number of treatments will begin to decline simply because the number of patients remaining untreated is shrinking.”

  1. Moon AM, Green PK, Berry K, Ioannou GN. Transformation of hepatitis Cantiviral treatment in a national healthcare system following the introduction ofdirect antiviral agents. Aliment Pharmacol Ther. 2017 May;45(9):1201-1212. doi:10.1111/apt.14021. Epub 2017 Mar 8. PubMed PMID: 28271521. 
  2. Ioannou GN, Beste LA, Chang MF, Green PK, Lowy E, Tsui JI, Su F, Berry K. Effectiveness of Sofosbuvir, Ledipasvir/Sofosbuvir, or Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir Regimens for Treatment of Patients With Hepatitis C in the Veterans Affairs National Health Care System. Gastroenterology. 2016 Sep;151(3):457-471.e5. doi: 10.1053/j.gastro.2016.05.049.  Epub 2016 Jun 4. PubMed PMID: 27267053; PubMed Central PMCID: PMC5341745.