Hepatitis C can be a chronic condition that leads to liver failure, and treatments often haven’t worked for patients who are also co-infected with HIV. Thanks to research led by the National Institute of Allergy and Infectious Diseases and Gilead Sciences, new therapies are now available that can cure even complicated cases of hepatitis C without serious side effects. Read on to learn how these discoveries were made and what they mean for patients around the world.
What is Hepatitis C?
Hepatitis C is a liver disease that, if left untreated, can lead to liver scarring (called “cirrhosis”), liver cancer, and eventual liver failure. Roughly 400,000 people in the United States and 5 million globally are infected with both hepatitis C virus (HCV) and HIV. People with HCV-HIV co-infection are three times more likely to develop cirrhosis or advanced liver disease than people infected with HCV alone, and hepatitis C is a leading cause of death for people with HCV-HIV co-infection.
Some people who get hepatitis C virus have it for a short time (up to six months) and then get better on their own. This is called acute hepatitis C. But most people—about 75 to 85 percent—will go on to develop chronic, or long-term, hepatitis C, meaning the virus requires treatment.
Older Treatment Regimen Cured Few
In the past, the standard chronic hepatitis C treatment for people co-infected with HIV consisted of weekly injections of a medication called pegylated interferon and a daily dose of the drug ribavirin for 48 weeks. This regimen cured chronic hepatitis C only 20 percent of the time in people with HCV-HIV co-infection. What’s more, the treatment was associated with many side effects, from vomiting, diarrhea, muscle aches and headaches in the short term to depression, anemia, insomnia, weight loss, hair loss, and a drop in the number of infection-fighting white blood cells in the long term.
As a result, many physicians and their HCV-HIV co-infected patients did not try to treat chronic hepatitis C at all. Scientists have been working to fill the unmet need for a highly effective, safe and tolerable chronic hepatitis C treatment regimen for people with HCV-HIV co-infection.
First Steps toward a Viable Cure
In 2010, a new drug called sofosbuvir became available for the investigational treatment of certain types of chronic hepatitis C as part of combination therapy. Unlike interferon, which acts on the immune system, sofosbuvir acts directly on the virus and thus held promise for being more effective, safe, and tolerable than the older drug. Gilead Sciences, Inc. of Foster City, Calif., makes sofosbuvir, which is now FDA-approved and marketed as Sovaldi.
Gilead Sciences launched a clinical trial in 2012 to test the safety and efficacy of a daily regimen of sofosbuvir and ribavirin for treating chronic hepatitis C in people with HIV-HCV co-infection. The 223 participants were taking anti-HIV therapy and had not previously received treatment for hepatitis C. Investigators found that the regimen cured chronic hepatitis C 75 percent of the time in people who were treated for 24 weeks, but led to a cure less often in people who were treated for 12 weeks. Also, the regimen was associated with side effects related to ribavirin, including anemia, fatigue, insomnia, nausea, and headache.
NIH Study Aims for a Better Cure
To try to attain a higher cure rate with fewer side effects, scientists from the DC Partnership for AIDS Progress, of which the National Institutes of Health (NIH) is a part, launched a study in 2013 to evaluate the safety and efficacy of a simpler, relatively short regimen for treating chronic hepatitis C in people with HCV-HIV co-infection. The treatment consisted of sofosbuvir and a newer drug by Gilead Sciences, ledipasvir, taken in a single pill once daily for 12 weeks. Like sofosbuvir, ledipasvir also acts directly on the hepatitis C virus, but targets a different viral protein. The trial, called ERADICATE, was the first to treat HCV-HIV co-infection with a regimen that involved neither interferon nor ribavirin.
Led by Shyam Kottilil, M.D., Ph.D., then a NIAID researcher at NIH, the team found that the ledipasvir/sofosbuvir treatment regimen cured chronic hepatitis C in 49 of 50 participants, or 98 percent. The treatment had no serious side effects, and no one stopped taking the pill before completing the 12-week regimen. In addition, the therapy had no observed effect on the course or treatment of HIV infection. This advance was published in the Journal of the American Medical Association, and the drug is now FDA-approved and marketed by Gilead Sciences as Harvoni.
Curing the Toughest Cases
For safety reasons, the ERADICATE study purposely excluded people with cirrhosis and prior hepatitis C treatment experience. The effectiveness of the ledipasvir/sofosbuvir treatment regimen in such individuals remains an important concern because they represent a significant proportion of the HIV-HCV co-infected people who need treatment. A more recent study conducted by Gilead Sciences addressed this tougher-to-treat population, prescribing ledipasvir/sofosbuvir once daily for 12 weeks to 335 people with HCV-HIV co-infection, some of whom had cirrhosis or past hepatitis C treatment experience, and all of whom were on anti-HIV therapy. Investigators found a chronic hepatitis C cure rate of 96 percent with no serious side effects, boding well for the future treatment of many people with HCV-HIV co-infection.
Looking to the Future
According to Dr. Kottilil, additional studies are needed to determine whether there are any significant interactions between ledipasvir/sofosbuvir and commonly prescribed HIV medications that were not used in earlier studies.
Meanwhile, data from the ERADICATE study are being used to inform treatment in the NIH-led ASCEND clinical trial, which is examining whether primary care physicians and other health care providers can use ledipasvir/sofosbuvir as effectively as specialist physicians to treat people with either HIV-HCV co-infection or HCV infection alone.
In addition, the STOP-CO trial will determine whether ledipasvir/sofosbuvir can cure chronic hepatitis C in people with HIV-HCV co-infection who are awaiting or have just received a liver transplant due to advanced HCV-induced cirrhosis and liver failure. NIH and the University of California, San Francisco, are leading this study, which is scheduled to launch in June 2015.
MS Sulkowski, et al. Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection, JAMA doi:10.1001/jama.2014.7734 (2014).
A Osinusi et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. JAMA doi:10.1001/jama.2015.1373 (2015).
S Naggie et al. Ledipasvir/sofosbuvir for 12 weeks in patients coinfected with HCV and HIV-1. Abstract number 152LB. Presented at CROI 2015, Seattle, Feb. 26, 2015.