Patients with mental health issues are among those for whom the peg/riba treatment is often contraindicated, but they’re not the only ones to whom it poses risks. “People who have anemia at baseline can have severe anemia when ribavirin is administered and have to be monitored closely,” said Dr. Donald Anthony, a physician with the Cleveland VAMC and associate professor of medicine at Case Western Reserve University. “Some individuals have renal insufficiency or kidney dysfunction, and that makes things even more difficult, because the ribavirin is hard to dose in those individuals. So we do have a long track record of difficult situations where we’re unable to treat patients with interferon or ribavirin as we would like.”
Among those who are able to endure peg/riba and a direct acting antiviral agent combination therapy, about 50 to 80 percent are cured – the virus cleared from their bodies. The number whose infections persist, in addition to those for whom peg/riba is contraindicated, continue to comprise a significant fraction of people who continue to struggle with hepatitis C.
VA’s physicians and research scientists have led the way in searching for better hepatitis C treatments, in improving veterans’ access to these therapies, and in improving outcomes for patients who seek treatment. VA research ranges from basic molecular and biomedical studies of the hepatitis C virus to the overall effectiveness of VA’s systems of care.
“The VA has been a leader,” said Stapleton, “in the research showing that the integrated care system, with an infectious disease or hepatology provider having nursing support and social and psychological support, improves outcomes.”
In Cleveland, for example, researchers are conducting biomedical studies aimed at understanding the role of natural killer cells in fighting HCV infection, as well as clinical studies designed to explore why certain populations, such as the elderly, have worse clinical outcomes. In Iowa City, Stapleton and associates are engaged in vaccine-related research, exploring ways to modify HCV proteins that block or weaken the human immune response. Throughout the VA health system, health services researchers are conducting investigations designed to hone and customize therapies to individual circumstances, such as viral genotype (there are seven HCV genotypes), behavioral issues (such as chronic alcohol use, which reduces treatment effectiveness), or medical or mental health variables such as anemia or depression. VA research has shown, for example, that anemic patients can still benefit from treatment.
While protease inhibitors and polymerase inhibitors like sofosbuvir are very expensive, the VA’s policy is that decisions should be based on clinical indication, and it had begun 4,300 hepatitis C patients on the drugs as of August 2014. Courtesy of Gilead Sciences
“The VA has been a leader,” said Stapleton, “in the research showing that the integrated care system, with an infectious disease or hepatology provider having nursing support and social and psychological support, improves outcomes.”
Since 2001, guidance and outreach – for both providers and patients – has been provided through the VA’s four Hepatitis C Resource Centers, located in West Haven, Connecticut; Minneapolis; San Francisco; and Seattle. “Their job,” said Ross, “has been to provide educational resources for clinicians, standards, and treatment guidelines. They are also tasked with developing new models of care, ways of trying to make care more effective.” The VA is in the process of combining these centers into a single virtual center, whose expertise will be accessible from anywhere in the country. “We want to have people at different locations contribute to things,” said Ross, “because there is a lot of variation in practice patterns across the system.”
A New Era in Hepatitis C Treatment
VA researchers are also exploring the potential of a new class of drugs, polymerase inhibitors, which block a specific protein required to grow the hepatitis C virus. Polymerase inhibitors, which do not involve the kind of debilitating side effects associated with interferon, were approved for clinical use by the FDA in 2013.
“I’ve been an infectious disease physician for over 20 years,” he said, “and I never thought I’d see the day when we’d have a cure for this disease. We really have a window of opportunity to do something about it, and I think my goal and the program’s goal is to try and get access to treatment for as many veterans as quickly as possible.”
One of these polymerase inhibitors in particular, sofosbuvir, is a once-daily pill used as part of an antiviral combination treatment targeting HCV genotypes 1 (which accounts for 70 percent of HCV cases), 2, 3, and 4. Sofosbuvir will allow some patients to avoid the need for weekly interferon injections. While patients with genotype 1 will still be treated with interferon, the course of treatment will be a considerably shorter 12 weeks.
The results from the first clinical trials of regimens involving sofosbuvir and other polymerase inhibitors mark the beginning of the end of the standard interferon-based therapy. “The preliminary data from small – but in aggregate, pretty significant – studies show that if you can combine two classes, and even three, much like we do with HIV therapy, you have very high cure rates,” said Stapleton. “Over 90 percent, even in people that we used to call the hard-to-treat. As we move toward this interferon-free treatment as the standard, it will improve our cure rates – doubling them, for almost everyone who is able to take the therapy.”
As of August 2014, the VA had begun about 4,300 hepatitis C patients on a regimen involving sofosbuvir, manufactured under the trade name Sovaldi by Gilead Sciences and another new drug, the protease inhibitor simeprevir. Both drugs are incredibly expensive, at $1,000 a day. Ross estimates that by the end of fiscal year 2014, the VA will have spent nearly $300 million on the regimen. “The VA policy on both these drugs,” he said, “is that decisions should be made on clinical indication, not on cost.”
Being on the cusp of an interferon-free era in hepatitis C treatment, said Ross, is one of the most exciting times in his career. “I’ve been an infectious disease physician for over 20 years,” he said, “and I never thought I’d see the day when we’d have a cure for this disease. We really have a window of opportunity to do something about it, and I think my goal and the program’s goal is to try and get access to treatment for as many veterans as quickly as possible.”
This article first appeared in The Year in Veterans Affairs & Military Medicine: 2014-2015 Edition.