HCV coinfections can be safely treated in patients with HIV

BOSTON – Patients with HIV and hepatitis C coinfection had high levels of sustained viral response with regimens combining select antiretroviral agents with telaprevir, pegylated interferon, and ribavirin, said investigators at the annual meeting of the American Association for the Study of Liver Diseases.

The key to avoiding adverse drug interactions between telaprevir (Incivek) and highly active antiretroviral therapy (HAART) regimens is careful selection of HIV therapy, said Dr. Mark Sulkowski, medical director of the viral hepatitis center at Johns Hopkins University in Baltimore.

Dr. Sulkowski and his colleagues showed in a randomized phase III study that a combination of specific antiretroviral agents with telaprevir and pegylated interferon alfa-2a (PEG-IFN) and ribavirin (RBV) was associated with a 74% SVR₂₄ rate, compared with HAART and PEG-IFN only.

"Overall, 74% of patients treated with telaprevir in combination with peg-interferon and ribavirin achieved SVR [sustained virological response], compared to 45% of those treated with placebo. Drug interactions with telaprevir and selected antiretroviral therapies, specifically atazanavir/ritonavir and efavirenz, were not clinically meaningful," Dr. Sulkowski said.

A separate study by European investigators showed that the likelihood that patients with HIV/HCV coinfection will clear HCV from serum may depend on the presence of ribavirin in a regimen, and on HCV genotype.

"Ribavirin is important in the management of acute hepatitis C in HIV-positive patients. Almost all patients with genotype 2 and 3 infections were able to clear virus with combination therapy [PEG-IFN and RBV]," said lead investigator Dr. Christoph Boesecke of the University of Bonn, Germany.

Safety Concerns

Some infectious disease specialists have expressed concern that the addition of a direct-acting antiviral agent in combination with PEG-IFN/RBV could compromise the efficacy and/or safety of a HAART regimen.

To test the HAART/direct-acting antiviral agent combination, Dr. Sulkowski and his colleagues enrolled patients with HIV/HCV coinfection in a two-part study. In part A, patients were assigned on a 1:1 ratio to receive either telaprevir or placebo, each with PEG-IFN/RBV.

In part B, patients on a HAART regimen (either a combination of efavirenz, tenofovir, and emtricitabine or ritonavir-boosted atazanavir, tenofovir, and emtricitabine or lamivudine) were assigned on a 2:1 basis to receive telaprevir or placebo plus PEG-IFN/RBV. All patients were treated for 48 weeks, with an additional 24 weeks of follow-up.

HCV RNA levels on study were measured at various time points, and the investigators looked for drug interactions, adverse events, viral breakthrough, and other clinical measures.

At 24 weeks post treatment, the HCV sustained virologic response rate (SVR₂₄) among patients treated with telaprevir and PEG-IFN/RBV but not an antiretroviral therapy was 71%, compared with 33% among those treated with placebo and PEG-IFN/RBV.

Among patients on the HAART regimen containing efavirenz plus telaprevir and PEG-IFN/RBV, 69% had an SVR₂₄, compared with 38% of those who received the same HAART regimen without telaprevir. Among those on the atazanavir-containing regimen, 73% had an SVR₂₄, compared with 50% of controls who received only PEG-IFN/RBV plus HAART.

The serum concentrations of both atazanavir and efavirenz were similar whether the patients had received telaprevir or not, and there were no cases of HIV viral breakthrough, although CD4 cell counts decreased among patients taking PEG-IFN/RBV and either telaprevir or placebo. Nonetheless, investigators did not see HIV-related adverse events, Dr. Sulkowski said.

Patients on efavirenz did require a telaprevir dose increase, but the required increase was adequate for maintaining exposure to the direct-acting antiviral agent, he added.

Genotype Matters

Dr. Boesecke and his colleagues in the European AIDS Treatment Network looked at the effect of HCV genotype and ribavirin on SVR rates in the treatment of coinfected patients. They reported on 303 HIV-infected men from the Austria, France, Germany, and the United Kingdom who had been diagnosed with acute HCV infections. Of this group, 273 were treated with PEG-IFN/RBV, and 30 were treated with PEG-IFN alone. In all, 88% of the patients who received ribavirin had weight-based doses (1,000 mg for those 75 kg and under, and 1,200 mg for those over 75 kg).

A majority of the patients (69%) were infected with genotype 1; 4% had genotype 2; 11% had genotype 3; and 16% had genotype 4 infections. About one-third of patients had 24 weeks of therapy, and the remaining third had 48 weeks. Median time from HCV diagnosis to the start of treatment was about 10 weeks.

Among all patients, 52% of those received PEG-IFN alone, and 52% of those who also received ribavirin had a rapid virologic response (RVR), defined as HCV RNA negative at 4 weeks. Respective SVR₂₄ rates were 66.7% and 69.6%.

When the investigators broke it out by genotype, however, they found that while the addition of ribavirin did not significantly change either RVR or SVR₂₄ rates among patients with genotype 1 or 3 infections, 60% of patients with genotype 2 or 3 infections on PEG-IFN monotherapy had a 60% SVR^24,, whereas those on PEG-IFN/RBV had a 94% SVR₂₄. indicating a significant benefit to adding RBV (P = .016). The RVR rates were not significantly different in these patients, however.

There were no significant differences in either the total number or severity of adverse events among the various genotypes. In 10% of all cases a ribavirin dose reduction was required, and interferon dose reductions were required in 6% of cases.

Toxicities required stopping HCV therapy in 17 patients (6%).

"We saw high sustained virologic response rates if you treat hepatitis C early on, when it’s still acute, compared to when the disease is left to a chronic course in HIV patients," said Dr. Boesecke

Dr. Sulkowski’s study was supported by Vertex Pharmaceuticals. He is a consultant to the company and has received grant and research support from it. Dr. Boesecke’s study was supported by the European AIDS Treatment Network. He reported no conflict of interest.

BOSTON – Patients with HIV and hepatitis C coinfection had high levels of sustained viral response with regimens combining select antiretroviral agents with telaprevir, pegylated interferon, and ribavirin, said investigators at the annual meeting of the American Association for the Study of Liver Diseases.

The key to avoiding adverse drug interactions between telaprevir (Incivek) and highly active antiretroviral therapy (HAART) regimens is careful selection of HIV therapy, said Dr. Mark Sulkowski, medical director of the viral hepatitis center at Johns Hopkins University in Baltimore.

Dr. Sulkowski and his colleagues showed in a randomized phase III study that a combination of specific antiretroviral agents with telaprevir and pegylated interferon alfa-2a (PEG-IFN) and ribavirin (RBV) was associated with a 74% SVR₂₄ rate, compared with HAART and PEG-IFN only.

"Overall, 74% of patients treated with telaprevir in combination with peg-interferon and ribavirin achieved SVR [sustained virological response], compared to 45% of those treated with placebo. Drug interactions with telaprevir and selected antiretroviral therapies, specifically atazanavir/ritonavir and efavirenz, were not clinically meaningful," Dr. Sulkowski said.

A separate study by European investigators showed that the likelihood that patients with HIV/HCV coinfection will clear HCV from serum may depend on the presence of ribavirin in a regimen, and on HCV genotype.

"Ribavirin is important in the management of acute hepatitis C in HIV-positive patients. Almost all patients with genotype 2 and 3 infections were able to clear virus with combination therapy [PEG-IFN and RBV]," said lead investigator Dr. Christoph Boesecke of the University of Bonn, Germany.

Safety Concerns

Some infectious disease specialists have expressed concern that the addition of a direct-acting antiviral agent in combination with PEG-IFN/RBV could compromise the efficacy and/or safety of a HAART regimen.

To test the HAART/direct-acting antiviral agent combination, Dr. Sulkowski and his colleagues enrolled patients with HIV/HCV coinfection in a two-part study. In part A, patients were assigned on a 1:1 ratio to receive either telaprevir or placebo, each with PEG-IFN/RBV.

In part B, patients on a HAART regimen (either a combination of efavirenz, tenofovir, and emtricitabine or ritonavir-boosted atazanavir, tenofovir, and emtricitabine or lamivudine) were assigned on a 2:1 basis to receive telaprevir or placebo plus PEG-IFN/RBV. All patients were treated for 48 weeks, with an additional 24 weeks of follow-up.

HCV RNA levels on study were measured at various time points, and the investigators looked for drug interactions, adverse events, viral breakthrough, and other clinical measures.

At 24 weeks post treatment, the HCV sustained virologic response rate (SVR₂₄) among patients treated with telaprevir and PEG-IFN/RBV but not an antiretroviral therapy was 71%, compared with 33% among those treated with placebo and PEG-IFN/RBV.

Among patients on the HAART regimen containing efavirenz plus telaprevir and PEG-IFN/RBV, 69% had an SVR₂₄, compared with 38% of those who received the same HAART regimen without telaprevir. Among those on the atazanavir-containing regimen, 73% had an SVR₂₄, compared with 50% of controls who received only PEG-IFN/RBV plus HAART.

The serum concentrations of both atazanavir and efavirenz were similar whether the patients had received telaprevir or not, and there were no cases of HIV viral breakthrough, although CD4 cell counts decreased among patients taking PEG-IFN/RBV and either telaprevir or placebo. Nonetheless, investigators did not see HIV-related adverse events, Dr. Sulkowski said.

Patients on efavirenz did require a telaprevir dose increase, but the required increase was adequate for maintaining exposure to the direct-acting antiviral agent, he added.

Genotype Matters

Dr. Boesecke and his colleagues in the European AIDS Treatment Network looked at the effect of HCV genotype and ribavirin on SVR rates in the treatment of coinfected patients. They reported on 303 HIV-infected men from the Austria, France, Germany, and the United Kingdom who had been diagnosed with acute HCV infections. Of this group, 273 were treated with PEG-IFN/RBV, and 30 were treated with PEG-IFN alone. In all, 88% of the patients who received ribavirin had weight-based doses (1,000 mg for those 75 kg and under, and 1,200 mg for those over 75 kg).

A majority of the patients (69%) were infected with genotype 1; 4% had genotype 2; 11% had genotype 3; and 16% had genotype 4 infections. About one-third of patients had 24 weeks of therapy, and the remaining third had 48 weeks. Median time from HCV diagnosis to the start of treatment was about 10 weeks.

Among all patients, 52% of those received PEG-IFN alone, and 52% of those who also received ribavirin had a rapid virologic response (RVR), defined as HCV RNA negative at 4 weeks. Respective SVR₂₄ rates were 66.7% and 69.6%.

When the investigators broke it out by genotype, however, they found that while the addition of ribavirin did not significantly change either RVR or SVR₂₄ rates among patients with genotype 1 or 3 infections, 60% of patients with genotype 2 or 3 infections on PEG-IFN monotherapy had a 60% SVR^24,, whereas those on PEG-IFN/RBV had a 94% SVR₂₄. indicating a significant benefit to adding RBV (P = .016). The RVR rates were not significantly different in these patients, however.

There were no significant differences in either the total number or severity of adverse events among the various genotypes. In 10% of all cases a ribavirin dose reduction was required, and interferon dose reductions were required in 6% of cases.

Toxicities required stopping HCV therapy in 17 patients (6%).

"We saw high sustained virologic response rates if you treat hepatitis C early on, when it’s still acute, compared to when the disease is left to a chronic course in HIV patients," said Dr. Boesecke

Dr. Sulkowski’s study was supported by Vertex Pharmaceuticals. He is a consultant to the company and has received grant and research support from it. Dr. Boesecke’s study was supported by the European AIDS Treatment Network. He reported no conflict of interest.

BOSTON – Patients with HIV and hepatitis C coinfection had high levels of sustained viral response with regimens combining select antiretroviral agents with telaprevir, pegylated interferon, and ribavirin, said investigators at the annual meeting of the American Association for the Study of Liver Diseases.

The key to avoiding adverse drug interactions between telaprevir (Incivek) and highly active antiretroviral therapy (HAART) regimens is careful selection of HIV therapy, said Dr. Mark Sulkowski, medical director of the viral hepatitis center at Johns Hopkins University in Baltimore.

Dr. Sulkowski and his colleagues showed in a randomized phase III study that a combination of specific antiretroviral agents with telaprevir and pegylated interferon alfa-2a (PEG-IFN) and ribavirin (RBV) was associated with a 74% SVR₂₄ rate, compared with HAART and PEG-IFN only.

"Overall, 74% of patients treated with telaprevir in combination with peg-interferon and ribavirin achieved SVR [sustained virological response], compared to 45% of those treated with placebo. Drug interactions with telaprevir and selected antiretroviral therapies, specifically atazanavir/ritonavir and efavirenz, were not clinically meaningful," Dr. Sulkowski said.

A separate study by European investigators showed that the likelihood that patients with HIV/HCV coinfection will clear HCV from serum may depend on the presence of ribavirin in a regimen, and on HCV genotype.

"Ribavirin is important in the management of acute hepatitis C in HIV-positive patients. Almost all patients with genotype 2 and 3 infections were able to clear virus with combination therapy [PEG-IFN and RBV]," said lead investigator Dr. Christoph Boesecke of the University of Bonn, Germany.

Safety Concerns

Some infectious disease specialists have expressed concern that the addition of a direct-acting antiviral agent in combination with PEG-IFN/RBV could compromise the efficacy and/or safety of a HAART regimen.

To test the HAART/direct-acting antiviral agent combination, Dr. Sulkowski and his colleagues enrolled patients with HIV/HCV coinfection in a two-part study. In part A, patients were assigned on a 1:1 ratio to receive either telaprevir or placebo, each with PEG-IFN/RBV.

In part B, patients on a HAART regimen (either a combination of efavirenz, tenofovir, and emtricitabine or ritonavir-boosted atazanavir, tenofovir, and emtricitabine or lamivudine) were assigned on a 2:1 basis to receive telaprevir or placebo plus PEG-IFN/RBV. All patients were treated for 48 weeks, with an additional 24 weeks of follow-up.

HCV RNA levels on study were measured at various time points, and the investigators looked for drug interactions, adverse events, viral breakthrough, and other clinical measures.

At 24 weeks post treatment, the HCV sustained virologic response rate (SVR₂₄) among patients treated with telaprevir and PEG-IFN/RBV but not an antiretroviral therapy was 71%, compared with 33% among those treated with placebo and PEG-IFN/RBV.

Among patients on the HAART regimen containing efavirenz plus telaprevir and PEG-IFN/RBV, 69% had an SVR₂₄, compared with 38% of those who received the same HAART regimen without telaprevir. Among those on the atazanavir-containing regimen, 73% had an SVR₂₄, compared with 50% of controls who received only PEG-IFN/RBV plus HAART.

The serum concentrations of both atazanavir and efavirenz were similar whether the patients had received telaprevir or not, and there were no cases of HIV viral breakthrough, although CD4 cell counts decreased among patients taking PEG-IFN/RBV and either telaprevir or placebo. Nonetheless, investigators did not see HIV-related adverse events, Dr. Sulkowski said.

Patients on efavirenz did require a telaprevir dose increase, but the required increase was adequate for maintaining exposure to the direct-acting antiviral agent, he added.

Genotype Matters

Dr. Boesecke and his colleagues in the European AIDS Treatment Network looked at the effect of HCV genotype and ribavirin on SVR rates in the treatment of coinfected patients. They reported on 303 HIV-infected men from the Austria, France, Germany, and the United Kingdom who had been diagnosed with acute HCV infections. Of this group, 273 were treated with PEG-IFN/RBV, and 30 were treated with PEG-IFN alone. In all, 88% of the patients who received ribavirin had weight-based doses (1,000 mg for those 75 kg and under, and 1,200 mg for those over 75 kg).

A majority of the patients (69%) were infected with genotype 1; 4% had genotype 2; 11% had genotype 3; and 16% had genotype 4 infections. About one-third of patients had 24 weeks of therapy, and the remaining third had 48 weeks. Median time from HCV diagnosis to the start of treatment was about 10 weeks.

Among all patients, 52% of those received PEG-IFN alone, and 52% of those who also received ribavirin had a rapid virologic response (RVR), defined as HCV RNA negative at 4 weeks. Respective SVR₂₄ rates were 66.7% and 69.6%.

When the investigators broke it out by genotype, however, they found that while the addition of ribavirin did not significantly change either RVR or SVR₂₄ rates among patients with genotype 1 or 3 infections, 60% of patients with genotype 2 or 3 infections on PEG-IFN monotherapy had a 60% SVR^24,, whereas those on PEG-IFN/RBV had a 94% SVR₂₄. indicating a significant benefit to adding RBV (P = .016). The RVR rates were not significantly different in these patients, however.

There were no significant differences in either the total number or severity of adverse events among the various genotypes. In 10% of all cases a ribavirin dose reduction was required, and interferon dose reductions were required in 6% of cases.

Toxicities required stopping HCV therapy in 17 patients (6%).

"We saw high sustained virologic response rates if you treat hepatitis C early on, when it’s still acute, compared to when the disease is left to a chronic course in HIV patients," said Dr. Boesecke

Dr. Sulkowski’s study was supported by Vertex Pharmaceuticals. He is a consultant to the company and has received grant and research support from it. Dr. Boesecke’s study was supported by the European AIDS Treatment Network. He reported no conflict of interest.