Some HCV patients still difficult to treat

Novel direct-acting antiviral (DAA) agents approved for the treatment of hepatitis C virus (HCV) have achieved unprecedented rates of sustained virological response and, in effect, enacted a functional cure. However, DAAs appear to have a less robust effect in a number of “difficult-to-treat” patients.

A new review summarizes the key issues with differing drug regimens and provides a practical guide to additional treatment strategies that are available for these patients, as well as evidence for the potential role of experimental DAAs.

The researchers reported their results in December 15, 2015 Current Opinion in Infectious Diseases.

The advent of novel DAA agents with broader genotypic activity, greater antiviral potency, and higher barriers to resistance present an opportunity to improve outcomes in patients with limited treatment options, such as patients with end-stage renal disease.

Treatment is still problematic in HCV patients with genotype 3 (G3) infection, cirrhotic disease, and those with more treatment experience.

“G3 has been the most difficult genotype to target with first-generations DAAs, presumably reflecting changes in the target proteins in G3, which make this virus less susceptible to the action of the block on replication,” said senior author Stephen Ryder, MD, of the University of Nottingham Digestive Diseases Centre, Queens Medical Centre, Nottingham, UK, told Medical Economics. “The next generation of drugs will have greater cross genotype activity, and we should see G3 results hitting similar levels to genotype 1 (G1).”

He noted that in combination with sofosbuvir, the novel nonstructural protein 5A inhibitor daclatasvir has demonstrated high efficacy in the treatment of non-cirrhotic G3 infection.

Historically, patients with advanced liver disease have always been less likely to respond to treatment. “The exact reason is not known, but it may be due to distribution of the drug in a cirrhotic liver, a longer infection with HCV affecting viral diversity and drug sensitivity or simply that sick people can take less drug,” Ryder said. “The effect of cirrhosis now is modest in G1, and even in G3 really poorer results are only seen in those with liver failure.”

The use of DAAs has revolutionized post-liver transplant responses. “Almost all G1 patients will be cured with oral therapy and even G3 responses now are excellent,” he said.

A number of clinical trials are now looking at different drug regimens in patients co-infected with HCV and human immunodeficiency virus (HIV). “None of the trials show poorer response. This has led regulators now to not regard HIV-infected people as a harder-to-treat group,” Ryder said.

Newer novel DAAs are expected to further expand therapy for difficult-to-treat groups. “We will see better drugs against G3. The goal is to use drugs with better activity against these viral strains,” he said.

Ryder emphasized, it is “vital to diagnose HCV infection as now we can cure nearly everyone. We should think of testing anyone with a potential risk factor, such as injecting drugs, birth in a high-risk country for medical transmission, such as Egypt or Pakistan, or anyone who has had blood products prior to 1991.”