EACS 2015: Sofosbuvir/ Ledipasvir for 8 Weeks Cures Most Hard-to-Treat Hepatitis C in Real Life

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Most hepatitis C patients in the GECCO German hepatitis C cohort who were treated with sofosbuvir/ledipasvir (Harvoni) for 8 weeks in a real-world clinical setting achieved sustained virological response, even those who are advised to stay on treatment for 12 weeks due to factors such as liver cirrhosis, prior treatment experience, and high HCV viral load, according to a presentation last week at the 15th European AIDS Conference in Barcelona.

The advent of direct-acting antiviral agents in interferon-free regimens has brought about a revolution in hepatitis C treatment, but there is still room to improve therapy, for example making treatment shorter and offering better options for the most difficult-to-treat patients. While 12-week post-treatment sustained virological response (SVR12) rates now exceed 90% in clinical trials, real-world experience does not always match up.

Patrick Ingiliz from the Center for Infectiology in Berlin reported findings from an analysis of real-life hepatitis C treatment using DAAs in the GECCO cohort, an ongoing multicenter cohort that includes patients at 8 sites in Germany.

Short-course DAA therapy might be an attractive option to reduce treatment costs or reduce the duration of drug toxicity, the researchers noted as background.

U.S. prescribing information for Gilead Science's sofosbuvir/ledipasvir coformulation, marketed as Harvoni, states that previously untreated people with HCV genotype 1, with or without cirrhosis, and treatment-experienced patients without cirrhosis, should take sofosbuvir/ledipasvir for 12 weeks. Treatment-experienced people with cirrhosis should extend treatment to 24 weeks, while treatment-naive people without cirrhosis and low HCV viral load can consider shortening it to 8 weeks. Among non-cirrhotic treatment-naive participants in the ION-3 trial, SVR12 rates were 94% using an 8-week regimen and 96% using a 12-week regimen; people in the 8-week arm were more likely to relapse after finishing treatment.

U.S. and European treatment guidelines also recommend sofosbuvir/ledipasvir for people with HCV genotype 4. Experts now recommend that HIV/HCV coinfected people should receive the same hepatitis C treatment regimens as those with HCV alone, after taking into account potential interactions with antiretroviral drugs.

GECCO was started in February 2014 and more than 1000 patients have started interferon-free DAA treatment to date. The current analysis focused on 148 participants (13% of the total) treated with sofosbuvir/ledipasvir for 8 weeks.

In this subgroup half were men, the median age was 52 years, and a third had injection drug use as a transmission risk. Almost all (97%) had HCV genotype 1, with 2% having genotype 4. Median pre-treatment HCV viral load was 810,000 IU/mL, 18% had received prior hepatitis C treatment, and 3% had liver cirrhosis according to FibroScan or APRI biomarker scores.

The group included 28 HIV/HCV coinfected patients (19% of the total) with a median CD4 count of 531 cells/mm3. Compared to the group as a whole, coinfected participants were more likely to be men (82%), more likely to have gotten HCV via sex (50%), and more likely to have HCV genotype 4 (11%). They had lower a median HCV viral load (490,000 IU/mL) and 2 people (7%) had cirrhosis.

Ingiliz reported SVR4 rates at 4 weeks post-treatment for 105 patients who had reached this time point, as well as SVR12 results for 70 patients who had reached 12 weeks post-treatment. SVR4 is not yet considered a cure, as a small proportion of people still relapse after this point.

Results

Based on these findings the researchers concluded, "Sofosbuvir plus ledipasvir for 8 weeks achieved excellent response rates in a German real-life setting," adding that, "HIV coinfected patients responded as well as HCV monoinfected patients."

Ingiliz noted that SVR rates were high even for participants who were treated "outside the recommendations" for this short regimen, including people with treatment experience, cirrhosis, high viral load, and genotype 4.

Asked whether these results show that sofosbuvir/ledipasvir can be used outside of current recommendations, Ingiliz replied he would not advise doing so. "Maybe from a cost perspective, but not from a virological one," he said. "People with high viral load may still need longer treatment."

10/28/15

Reference

P Ingiliz, S Christensen, S Mauss, et al. Sofosbuvir Plus Ledipasvir for 8 Weeks in HCV-mono- and HIV-HCV-coinfected Patients - Results from the German Hepatitis C Cohort (GECCO). 15th European AIDS Conference. Barcelona, October 21-24, 2015. Abstract PS7/5.