Sofosbuvir achieves sustained response in patients with hepatitis C and HIV

Treatment with the interferon-free oral nucleotide analog sofosbuvir plus ribavirin achieved high rates of sustained virologic response in patients with HIV coinfected with hepatitis C, according to data from an open-label phase III study.

Researchers observed an 82% response rate among treatment-naive patients coinfected with hepatitis C virus (HCV) genotype 1 and HIV, 12 weeks after they completed a 24-week course of therapy with sofosbuvir and ribavirin.

Among treatment-naive patients with HCV genotype 2 who received 12 weeks of treatment, 88% achieved a sustained virologic response at 12 weeks (SVR12) after treatment, and among treatment-experienced patients with HCV genotype 2, 92% achieved the same after 24 weeks of treatment.

The study was published July 19 in JAMA, coincident with the start of the 20th International AIDS Conference in Melbourne.

Treatment of patients coinfected with HIV and HCV, using pegylated interferon and ribavirin with or without an HCV NS3/4A serine protease inhibitor, telaprevir, or boceprevir, has previously been hampered by complex dosing, poor tolerability and drug interactions between HCV medications and antiretrovirals.

Sofosbuvir has shown little or no interaction with a range of antiretroviral drugs and has also been shown in previous studies to achieve a high rate of response.

"In our coinfected patient population, patients with HCV genotype 1 and characteristics that have historically been considered difficult to cure had high rates of SVR12 following receipt of the 24-week treatment regimen of sofosbuvir and ribavirin," wrote Dr. Mark S. Sulkowski of Johns Hopkins University, Baltimore, and his colleagues.

The open-label, uncontrolled, and nonrandomized trial enrolled 223 patients with HIV and HCV – 182 of whom had not previously been treated for HCV – and treated them with either 12 or 24 weeks’ treatment with 400 mg of oral sofosbuvir daily and a twice-daily, weight-based oral dose of ribavirin.

The strongest predictor of achieving SVR12 was completion of the treatment regimen.

"No S282T mutations were detected in patients with viral relapse or breakthrough, confirming the high barrier to resistance demonstrated in other studies of sofosbuvir," the researchers reported.

While 3% of patients discontinued HCV treatment because of adverse events, there were no serious adverse events attributable to the drug regimen (JAMA 2014, July 19 [doi:10.1001/jama.2014.7734]).

The most common side effects in all treatment groups were fatigue, insomnia, nausea, and headache; some patients showed decreases in hemoglobin and 19% of patients had their dose of ribavirin reduced.

Among patients not receiving antiretroviral therapy at baseline, there were no significant changes in viral load, but of the patients taking antiretrovirals, two experienced HIV viral breakthroughs but in both cases, poor adherence to antiretrovirals was the likely cause.

The authors stressed that there were relatively few women, patients with cirrhosis, or patients with advanced HIV disease enrolled in the study, so the results could not necessarily be generalized among these patients.

The study was funded by Gilead Sciences, and the authors reported a range of grants and other fees from the pharmaceutical industry, including Gilead.

Treatment with the interferon-free oral nucleotide analog sofosbuvir plus ribavirin achieved high rates of sustained virologic response in patients with HIV coinfected with hepatitis C, according to data from an open-label phase III study.

Researchers observed an 82% response rate among treatment-naive patients coinfected with hepatitis C virus (HCV) genotype 1 and HIV, 12 weeks after they completed a 24-week course of therapy with sofosbuvir and ribavirin.

Among treatment-naive patients with HCV genotype 2 who received 12 weeks of treatment, 88% achieved a sustained virologic response at 12 weeks (SVR12) after treatment, and among treatment-experienced patients with HCV genotype 2, 92% achieved the same after 24 weeks of treatment.

The study was published July 19 in JAMA, coincident with the start of the 20th International AIDS Conference in Melbourne.

Treatment of patients coinfected with HIV and HCV, using pegylated interferon and ribavirin with or without an HCV NS3/4A serine protease inhibitor, telaprevir, or boceprevir, has previously been hampered by complex dosing, poor tolerability and drug interactions between HCV medications and antiretrovirals.

Sofosbuvir has shown little or no interaction with a range of antiretroviral drugs and has also been shown in previous studies to achieve a high rate of response.

"In our coinfected patient population, patients with HCV genotype 1 and characteristics that have historically been considered difficult to cure had high rates of SVR12 following receipt of the 24-week treatment regimen of sofosbuvir and ribavirin," wrote Dr. Mark S. Sulkowski of Johns Hopkins University, Baltimore, and his colleagues.

The open-label, uncontrolled, and nonrandomized trial enrolled 223 patients with HIV and HCV – 182 of whom had not previously been treated for HCV – and treated them with either 12 or 24 weeks’ treatment with 400 mg of oral sofosbuvir daily and a twice-daily, weight-based oral dose of ribavirin.

The strongest predictor of achieving SVR12 was completion of the treatment regimen.

"No S282T mutations were detected in patients with viral relapse or breakthrough, confirming the high barrier to resistance demonstrated in other studies of sofosbuvir," the researchers reported.

While 3% of patients discontinued HCV treatment because of adverse events, there were no serious adverse events attributable to the drug regimen (JAMA 2014, July 19 [doi:10.1001/jama.2014.7734]).

The most common side effects in all treatment groups were fatigue, insomnia, nausea, and headache; some patients showed decreases in hemoglobin and 19% of patients had their dose of ribavirin reduced.

Among patients not receiving antiretroviral therapy at baseline, there were no significant changes in viral load, but of the patients taking antiretrovirals, two experienced HIV viral breakthroughs but in both cases, poor adherence to antiretrovirals was the likely cause.

The authors stressed that there were relatively few women, patients with cirrhosis, or patients with advanced HIV disease enrolled in the study, so the results could not necessarily be generalized among these patients.

The study was funded by Gilead Sciences, and the authors reported a range of grants and other fees from the pharmaceutical industry, including Gilead.

Treatment with the interferon-free oral nucleotide analog sofosbuvir plus ribavirin achieved high rates of sustained virologic response in patients with HIV coinfected with hepatitis C, according to data from an open-label phase III study.

Researchers observed an 82% response rate among treatment-naive patients coinfected with hepatitis C virus (HCV) genotype 1 and HIV, 12 weeks after they completed a 24-week course of therapy with sofosbuvir and ribavirin.

Among treatment-naive patients with HCV genotype 2 who received 12 weeks of treatment, 88% achieved a sustained virologic response at 12 weeks (SVR12) after treatment, and among treatment-experienced patients with HCV genotype 2, 92% achieved the same after 24 weeks of treatment.

The study was published July 19 in JAMA, coincident with the start of the 20th International AIDS Conference in Melbourne.

Treatment of patients coinfected with HIV and HCV, using pegylated interferon and ribavirin with or without an HCV NS3/4A serine protease inhibitor, telaprevir, or boceprevir, has previously been hampered by complex dosing, poor tolerability and drug interactions between HCV medications and antiretrovirals.

Sofosbuvir has shown little or no interaction with a range of antiretroviral drugs and has also been shown in previous studies to achieve a high rate of response.

"In our coinfected patient population, patients with HCV genotype 1 and characteristics that have historically been considered difficult to cure had high rates of SVR12 following receipt of the 24-week treatment regimen of sofosbuvir and ribavirin," wrote Dr. Mark S. Sulkowski of Johns Hopkins University, Baltimore, and his colleagues.

The open-label, uncontrolled, and nonrandomized trial enrolled 223 patients with HIV and HCV – 182 of whom had not previously been treated for HCV – and treated them with either 12 or 24 weeks’ treatment with 400 mg of oral sofosbuvir daily and a twice-daily, weight-based oral dose of ribavirin.

The strongest predictor of achieving SVR12 was completion of the treatment regimen.

"No S282T mutations were detected in patients with viral relapse or breakthrough, confirming the high barrier to resistance demonstrated in other studies of sofosbuvir," the researchers reported.

While 3% of patients discontinued HCV treatment because of adverse events, there were no serious adverse events attributable to the drug regimen (JAMA 2014, July 19 [doi:10.1001/jama.2014.7734]).

The most common side effects in all treatment groups were fatigue, insomnia, nausea, and headache; some patients showed decreases in hemoglobin and 19% of patients had their dose of ribavirin reduced.

Among patients not receiving antiretroviral therapy at baseline, there were no significant changes in viral load, but of the patients taking antiretrovirals, two experienced HIV viral breakthroughs but in both cases, poor adherence to antiretrovirals was the likely cause.

The authors stressed that there were relatively few women, patients with cirrhosis, or patients with advanced HIV disease enrolled in the study, so the results could not necessarily be generalized among these patients.

The study was funded by Gilead Sciences, and the authors reported a range of grants and other fees from the pharmaceutical industry, including Gilead.