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Hepatitis C could be reduced by 90% or more in the United States by the year 2040 with the use of direct-acting antivirals, near-universal screening, and enhanced treatment capacity, according to a study in Clinical Infectious Diseases.

A research team led by Jeffrey Townsend, Ph.D., of Yale School of Public Health, New Haven, Conn., said that new direct-acting antivirals (DAAs) alone could reduce the prevalence of hepatitis C virus (HCV) by 80% by the year 2040. When near-universal screening and enhanced treatment capacity are added to the equation, HCV could be eliminated in the United States, though cost and reimbursement issues may impede implementation.

©Martynasfoto/thinkstockphotos.com

“The key finding is that a fourfold increase to the number of patients treated each year could virtually eliminate HCV from the noninjecting population within a decade,” said Dr. Townsend, senior author of the study, in a statement accompanying the study [Clin Infect Dis. 2015. doi: 10.1093/cid/civ894].

First author David Durham, Ph.D., also of the Yale School of Public Health, and his collaborators analyzed currently available data and constructed a sophisticated model to generate projections of how future DAA treatment will change HCV prevalence. Dr. Durham and his colleagues also built models to account for varying levels of screening in the general population and for people who inject drugs (PWIDs).

More than 5 million people with chronic hepatitis C infection are thought to live in the United States, and just about 100,000 of those currently receive treatment each year. The treatment burden and relatively low cure rate of interferon-based therapies have historically been significant impediments for many patients. New DAAs promise a sustained virologic response (SVR) in up to 95% of patients with a well-tolerated, once-daily, one-pill several-week regimen.

Without enhanced screening or treatment rates, the model predicted an 80% decline in U.S. HCV prevalence by the year 2040. The 80% benchmark would be reached by the year 2025 if the annual treatment rate increased to 400,000, with 256,315 fewer HCV-related deaths through 2040. Just doubling the treatment rate to 200,000 patients per year would result in an 80% decrease in HCV prevalence by 2031, with 143,055 fewer deaths by 2040.

However, “more than half of those with chronic HCV are unaware of their status, including up to two-thirds of people who inject drugs,” wrote Dr. Durham and his coauthors. Therefore, enhanced HCV screening, especially among PWIDs, could provide a significant further reduction in morbidity and mortality from HCV.

Targeted screening of PWIDs to achieve a 20% screening rate (compared with the current 4.1%), combined with a treatment rate of at least 30%, would yield a 90% reduction of prevalence in HCV by 2040. Universal screening, combined with a treatment rate of at least 20%, would achieve a 90% reduction in the incidence of new infections by 2040, according to the model.

The drop in prevalence in the models took into account not only an increased SVR rate, but also the reduced transmission rate when more persons with HCV achieve an SVR. This dynamic transmission analysis “captures the impact of treatment on both chronic disease and transmission dynamics, distinguishes screening and treatment as separate but related public health objectives, and accounts for underreporting … of national HCV prevalence,” according to Dr. Durham and his coauthors.

Morbidity and mortality were accounted for by projecting the number of HCV patients in each treatment and screening condition who would spontaneously clear disease, become chronically infected, develop increasing levels of liver disease and cirrhosis, require transplant, become reinfected, or die.

As always, real world considerations temper what’s achievable. For DAAs, a chief factor is the cost of the regimens, which currently hovers around $90,000. “The improvement of health outcomes expected from greater acceptance might be tempered by the high costs of treatment and by limited insurance coverage and willingness to treat PWIDs,” Dr. Durham and his coauthors wrote.

Study limitations included some “simplifying assumptions” in the modeling, which did not account for the varying incidence of fibrosis and transmissibility among different HCV genotypes. Still, wrote Dr. Durham and his collaborators, “our analysis provides a forecast for the potential impact of DAAs in reducing HCV-associated liver disease, demonstrating that achievable expansion of HCV treatment at current screening rates can substantially reduce morbidity and mortality.”

The study was funded by the Notsew Orm Sands Foundation and Merck. Dr. Durham, Dr. Galvani, and Dr. Townsend have consulted for and received research funding from Sanofi Pasteur and Merck. Dr. Elbasha is employed by Merck and holds stock and stock options in the company. The other authors reported no conflicts of interest.

koakes@frontlinemedcom.com

On Twitter @karioakes

Hepatitis C could be reduced by 90% or more in the United States by the year 2040 with the use of direct-acting antivirals, near-universal screening, and enhanced treatment capacity, according to a study in Clinical Infectious Diseases.

A research team led by Jeffrey Townsend, Ph.D., of Yale School of Public Health, New Haven, Conn., said that new direct-acting antivirals (DAAs) alone could reduce the prevalence of hepatitis C virus (HCV) by 80% by the year 2040. When near-universal screening and enhanced treatment capacity are added to the equation, HCV could be eliminated in the United States, though cost and reimbursement issues may impede implementation.

©Martynasfoto/thinkstockphotos.com

“The key finding is that a fourfold increase to the number of patients treated each year could virtually eliminate HCV from the noninjecting population within a decade,” said Dr. Townsend, senior author of the study, in a statement accompanying the study [Clin Infect Dis. 2015. doi: 10.1093/cid/civ894].

First author David Durham, Ph.D., also of the Yale School of Public Health, and his collaborators analyzed currently available data and constructed a sophisticated model to generate projections of how future DAA treatment will change HCV prevalence. Dr. Durham and his colleagues also built models to account for varying levels of screening in the general population and for people who inject drugs (PWIDs).

More than 5 million people with chronic hepatitis C infection are thought to live in the United States, and just about 100,000 of those currently receive treatment each year. The treatment burden and relatively low cure rate of interferon-based therapies have historically been significant impediments for many patients. New DAAs promise a sustained virologic response (SVR) in up to 95% of patients with a well-tolerated, once-daily, one-pill several-week regimen.

Without enhanced screening or treatment rates, the model predicted an 80% decline in U.S. HCV prevalence by the year 2040. The 80% benchmark would be reached by the year 2025 if the annual treatment rate increased to 400,000, with 256,315 fewer HCV-related deaths through 2040. Just doubling the treatment rate to 200,000 patients per year would result in an 80% decrease in HCV prevalence by 2031, with 143,055 fewer deaths by 2040.

However, “more than half of those with chronic HCV are unaware of their status, including up to two-thirds of people who inject drugs,” wrote Dr. Durham and his coauthors. Therefore, enhanced HCV screening, especially among PWIDs, could provide a significant further reduction in morbidity and mortality from HCV.

Targeted screening of PWIDs to achieve a 20% screening rate (compared with the current 4.1%), combined with a treatment rate of at least 30%, would yield a 90% reduction of prevalence in HCV by 2040. Universal screening, combined with a treatment rate of at least 20%, would achieve a 90% reduction in the incidence of new infections by 2040, according to the model.

The drop in prevalence in the models took into account not only an increased SVR rate, but also the reduced transmission rate when more persons with HCV achieve an SVR. This dynamic transmission analysis “captures the impact of treatment on both chronic disease and transmission dynamics, distinguishes screening and treatment as separate but related public health objectives, and accounts for underreporting … of national HCV prevalence,” according to Dr. Durham and his coauthors.

Morbidity and mortality were accounted for by projecting the number of HCV patients in each treatment and screening condition who would spontaneously clear disease, become chronically infected, develop increasing levels of liver disease and cirrhosis, require transplant, become reinfected, or die.

As always, real world considerations temper what’s achievable. For DAAs, a chief factor is the cost of the regimens, which currently hovers around $90,000. “The improvement of health outcomes expected from greater acceptance might be tempered by the high costs of treatment and by limited insurance coverage and willingness to treat PWIDs,” Dr. Durham and his coauthors wrote.

Study limitations included some “simplifying assumptions” in the modeling, which did not account for the varying incidence of fibrosis and transmissibility among different HCV genotypes. Still, wrote Dr. Durham and his collaborators, “our analysis provides a forecast for the potential impact of DAAs in reducing HCV-associated liver disease, demonstrating that achievable expansion of HCV treatment at current screening rates can substantially reduce morbidity and mortality.”

The study was funded by the Notsew Orm Sands Foundation and Merck. Dr. Durham, Dr. Galvani, and Dr. Townsend have consulted for and received research funding from Sanofi Pasteur and Merck. Dr. Elbasha is employed by Merck and holds stock and stock options in the company. The other authors reported no conflicts of interest.

koakes@frontlinemedcom.com

On Twitter @karioakes

Hepatitis C could be reduced by 90% or more in the United States by the year 2040 with the use of direct-acting antivirals, near-universal screening, and enhanced treatment capacity, according to a study in Clinical Infectious Diseases.

A research team led by Jeffrey Townsend, Ph.D., of Yale School of Public Health, New Haven, Conn., said that new direct-acting antivirals (DAAs) alone could reduce the prevalence of hepatitis C virus (HCV) by 80% by the year 2040. When near-universal screening and enhanced treatment capacity are added to the equation, HCV could be eliminated in the United States, though cost and reimbursement issues may impede implementation.

©Martynasfoto/thinkstockphotos.com

“The key finding is that a fourfold increase to the number of patients treated each year could virtually eliminate HCV from the noninjecting population within a decade,” said Dr. Townsend, senior author of the study, in a statement accompanying the study [Clin Infect Dis. 2015. doi: 10.1093/cid/civ894].

First author David Durham, Ph.D., also of the Yale School of Public Health, and his collaborators analyzed currently available data and constructed a sophisticated model to generate projections of how future DAA treatment will change HCV prevalence. Dr. Durham and his colleagues also built models to account for varying levels of screening in the general population and for people who inject drugs (PWIDs).

More than 5 million people with chronic hepatitis C infection are thought to live in the United States, and just about 100,000 of those currently receive treatment each year. The treatment burden and relatively low cure rate of interferon-based therapies have historically been significant impediments for many patients. New DAAs promise a sustained virologic response (SVR) in up to 95% of patients with a well-tolerated, once-daily, one-pill several-week regimen.

Without enhanced screening or treatment rates, the model predicted an 80% decline in U.S. HCV prevalence by the year 2040. The 80% benchmark would be reached by the year 2025 if the annual treatment rate increased to 400,000, with 256,315 fewer HCV-related deaths through 2040. Just doubling the treatment rate to 200,000 patients per year would result in an 80% decrease in HCV prevalence by 2031, with 143,055 fewer deaths by 2040.

However, “more than half of those with chronic HCV are unaware of their status, including up to two-thirds of people who inject drugs,” wrote Dr. Durham and his coauthors. Therefore, enhanced HCV screening, especially among PWIDs, could provide a significant further reduction in morbidity and mortality from HCV.

Targeted screening of PWIDs to achieve a 20% screening rate (compared with the current 4.1%), combined with a treatment rate of at least 30%, would yield a 90% reduction of prevalence in HCV by 2040. Universal screening, combined with a treatment rate of at least 20%, would achieve a 90% reduction in the incidence of new infections by 2040, according to the model.

The drop in prevalence in the models took into account not only an increased SVR rate, but also the reduced transmission rate when more persons with HCV achieve an SVR. This dynamic transmission analysis “captures the impact of treatment on both chronic disease and transmission dynamics, distinguishes screening and treatment as separate but related public health objectives, and accounts for underreporting … of national HCV prevalence,” according to Dr. Durham and his coauthors.

Morbidity and mortality were accounted for by projecting the number of HCV patients in each treatment and screening condition who would spontaneously clear disease, become chronically infected, develop increasing levels of liver disease and cirrhosis, require transplant, become reinfected, or die.

As always, real world considerations temper what’s achievable. For DAAs, a chief factor is the cost of the regimens, which currently hovers around $90,000. “The improvement of health outcomes expected from greater acceptance might be tempered by the high costs of treatment and by limited insurance coverage and willingness to treat PWIDs,” Dr. Durham and his coauthors wrote.

Study limitations included some “simplifying assumptions” in the modeling, which did not account for the varying incidence of fibrosis and transmissibility among different HCV genotypes. Still, wrote Dr. Durham and his collaborators, “our analysis provides a forecast for the potential impact of DAAs in reducing HCV-associated liver disease, demonstrating that achievable expansion of HCV treatment at current screening rates can substantially reduce morbidity and mortality.”

The study was funded by the Notsew Orm Sands Foundation and Merck. Dr. Durham, Dr. Galvani, and Dr. Townsend have consulted for and received research funding from Sanofi Pasteur and Merck. Dr. Elbasha is employed by Merck and holds stock and stock options in the company. The other authors reported no conflicts of interest.

koakes@frontlinemedcom.com

On Twitter @karioakes

SAN FRANCISCO – The prevalence of cirrhosis among patients in the United States infected with hepatitis C virus (HCV) is rising steeply, according to data presented at the annual meeting of the American Association for the Study of Liver Diseases (AASLD).

“While the overall prevalence of HCV in the United States has declined, the number of HCV patients with cirrhosis has risen significantly. As many patients with HCV are asymptomatic and unaware of their infection, the data underline the need for systematic HCV surveillance,” reported Dr. Prowpanga Udompop, a postdoctoral research fellow in gastroenterology at Stanford (Calif.) University.

In this study, the rates of cirrhosis were calculated from National Health and Nutrition Examination Survey (NHANES) data by using two surrogate indicators, the aspartate amino transferase to platelet ratio index (APRI) and the FIB-4 score. The rates of HCV and cirrhosis among those with HCV were compared for three eras, 1988-1994, 1999-2006, and 2007-2012.

A steady decline in HCV prevalence among the NHANES survey participants was observed over these three eras, falling from 1.5% in the first era to 1.2% in the second era and 1.0% in the third.

In contrast, the prevalence of cirrhosis among patients infected with HCV, according to estimates based on conventional APRI and FIB-4 thresholds for a high probability of cirrhosis, climbed steadily over this same period. By APRI score, the estimated prevalence of cirrhosis climbed from 6.6% in the first era to 7.6% and 17% in the next two eras, respectively. By FIB-4, the estimated rates, showing a very similar pattern and proportionality, rose sequentially from 8.6% to 10% and then to 16%.

In a logistic regression analysis, increasing age and increasing rates of diabetes mellitus among the HCV patients correlated with a rising prevalence of cirrhosis. For example, by odds ratio (OR), the risk of cirrhosis in those with diabetes was more than doubled as calculated with APRI score (OR, 2.33; 95% CI, 1.01-5.04) and more than tripled as calculated with FIB-4 (3.37; 95% CI, 1.24-9.5). Obesity was also strongly correlated with cirrhosis by APRI score (OR, 2.95; 95% CI, 1.15-7.57).

Neither race nor drinking status was significantly correlated with the increasing rates of cirrhosis as observed across the three eras using APRI score or the FIB-4 index.

The rapid and ongoing increase in the prevalence of cirrhosis in patients with HCV has important clinical implications, according to Dr. Udompap. By her estimates, 15% of HCV-infected patients aware of their diagnosis have cirrhosis, but the prevalence may be as high as 20% in those who are asymptomatic and undiagnosed.

Moreover, these rates are likely to continue to increase because of the increasing age and rising rates of obesity and diabetes among both the general population and patients infected with HCV. All three factors appear to contribute to the risk of HCV-associated cirrhosis. This suggests that although the national burden of HCV is declining, the rates of end-stage liver complications may increase without efforts to screen and initiate therapies that provide high rates of sustained virologic response.

“These data reinforce current guidelines for screening asymptomatic individuals and for systematic assessment for liver fibrosis in those diagnosed with HCV,” Dr. Udompap reported.

SAN FRANCISCO – The prevalence of cirrhosis among patients in the United States infected with hepatitis C virus (HCV) is rising steeply, according to data presented at the annual meeting of the American Association for the Study of Liver Diseases (AASLD).

“While the overall prevalence of HCV in the United States has declined, the number of HCV patients with cirrhosis has risen significantly. As many patients with HCV are asymptomatic and unaware of their infection, the data underline the need for systematic HCV surveillance,” reported Dr. Prowpanga Udompop, a postdoctoral research fellow in gastroenterology at Stanford (Calif.) University.

In this study, the rates of cirrhosis were calculated from National Health and Nutrition Examination Survey (NHANES) data by using two surrogate indicators, the aspartate amino transferase to platelet ratio index (APRI) and the FIB-4 score. The rates of HCV and cirrhosis among those with HCV were compared for three eras, 1988-1994, 1999-2006, and 2007-2012.

A steady decline in HCV prevalence among the NHANES survey participants was observed over these three eras, falling from 1.5% in the first era to 1.2% in the second era and 1.0% in the third.

In contrast, the prevalence of cirrhosis among patients infected with HCV, according to estimates based on conventional APRI and FIB-4 thresholds for a high probability of cirrhosis, climbed steadily over this same period. By APRI score, the estimated prevalence of cirrhosis climbed from 6.6% in the first era to 7.6% and 17% in the next two eras, respectively. By FIB-4, the estimated rates, showing a very similar pattern and proportionality, rose sequentially from 8.6% to 10% and then to 16%.

In a logistic regression analysis, increasing age and increasing rates of diabetes mellitus among the HCV patients correlated with a rising prevalence of cirrhosis. For example, by odds ratio (OR), the risk of cirrhosis in those with diabetes was more than doubled as calculated with APRI score (OR, 2.33; 95% CI, 1.01-5.04) and more than tripled as calculated with FIB-4 (3.37; 95% CI, 1.24-9.5). Obesity was also strongly correlated with cirrhosis by APRI score (OR, 2.95; 95% CI, 1.15-7.57).

Neither race nor drinking status was significantly correlated with the increasing rates of cirrhosis as observed across the three eras using APRI score or the FIB-4 index.

The rapid and ongoing increase in the prevalence of cirrhosis in patients with HCV has important clinical implications, according to Dr. Udompap. By her estimates, 15% of HCV-infected patients aware of their diagnosis have cirrhosis, but the prevalence may be as high as 20% in those who are asymptomatic and undiagnosed.

Moreover, these rates are likely to continue to increase because of the increasing age and rising rates of obesity and diabetes among both the general population and patients infected with HCV. All three factors appear to contribute to the risk of HCV-associated cirrhosis. This suggests that although the national burden of HCV is declining, the rates of end-stage liver complications may increase without efforts to screen and initiate therapies that provide high rates of sustained virologic response.

“These data reinforce current guidelines for screening asymptomatic individuals and for systematic assessment for liver fibrosis in those diagnosed with HCV,” Dr. Udompap reported.

SAN FRANCISCO – The prevalence of cirrhosis among patients in the United States infected with hepatitis C virus (HCV) is rising steeply, according to data presented at the annual meeting of the American Association for the Study of Liver Diseases (AASLD).

“While the overall prevalence of HCV in the United States has declined, the number of HCV patients with cirrhosis has risen significantly. As many patients with HCV are asymptomatic and unaware of their infection, the data underline the need for systematic HCV surveillance,” reported Dr. Prowpanga Udompop, a postdoctoral research fellow in gastroenterology at Stanford (Calif.) University.

In this study, the rates of cirrhosis were calculated from National Health and Nutrition Examination Survey (NHANES) data by using two surrogate indicators, the aspartate amino transferase to platelet ratio index (APRI) and the FIB-4 score. The rates of HCV and cirrhosis among those with HCV were compared for three eras, 1988-1994, 1999-2006, and 2007-2012.

A steady decline in HCV prevalence among the NHANES survey participants was observed over these three eras, falling from 1.5% in the first era to 1.2% in the second era and 1.0% in the third.

In contrast, the prevalence of cirrhosis among patients infected with HCV, according to estimates based on conventional APRI and FIB-4 thresholds for a high probability of cirrhosis, climbed steadily over this same period. By APRI score, the estimated prevalence of cirrhosis climbed from 6.6% in the first era to 7.6% and 17% in the next two eras, respectively. By FIB-4, the estimated rates, showing a very similar pattern and proportionality, rose sequentially from 8.6% to 10% and then to 16%.

In a logistic regression analysis, increasing age and increasing rates of diabetes mellitus among the HCV patients correlated with a rising prevalence of cirrhosis. For example, by odds ratio (OR), the risk of cirrhosis in those with diabetes was more than doubled as calculated with APRI score (OR, 2.33; 95% CI, 1.01-5.04) and more than tripled as calculated with FIB-4 (3.37; 95% CI, 1.24-9.5). Obesity was also strongly correlated with cirrhosis by APRI score (OR, 2.95; 95% CI, 1.15-7.57).

Neither race nor drinking status was significantly correlated with the increasing rates of cirrhosis as observed across the three eras using APRI score or the FIB-4 index.

The rapid and ongoing increase in the prevalence of cirrhosis in patients with HCV has important clinical implications, according to Dr. Udompap. By her estimates, 15% of HCV-infected patients aware of their diagnosis have cirrhosis, but the prevalence may be as high as 20% in those who are asymptomatic and undiagnosed.

Moreover, these rates are likely to continue to increase because of the increasing age and rising rates of obesity and diabetes among both the general population and patients infected with HCV. All three factors appear to contribute to the risk of HCV-associated cirrhosis. This suggests that although the national burden of HCV is declining, the rates of end-stage liver complications may increase without efforts to screen and initiate therapies that provide high rates of sustained virologic response.

“These data reinforce current guidelines for screening asymptomatic individuals and for systematic assessment for liver fibrosis in those diagnosed with HCV,” Dr. Udompap reported.

Shorter-course treatment with combinations of three or four different direct-acting antiviral agents achieved sustain viral response in 12 weeks (SVR12) in less than a third of patients with hepatitis C virus infection in an open-label, non-randomized, phase 2a proof-of-concept study.

SVR12 was achieved in 10 of 25 (40%) treatment-naive patients without cirrhosis who were treated with a 3-drug regimen consisting of ledipasvir and sofosbuvir plus GS-9451 (an NS3/4A protease inhibitor) for 4 weeks, and in 5 of 25 (20%) of 25 treatment-naive patients without cirrhosis treated with ledipasvir and sofosbuvir plus GS9451 and GS-9669 (a nonnucleoside NS5B polymerase inhibitor) for 4 weeks, Dr. Anita Kohli of the National Institutes of Health Clinical Center, Bethesda, Md. and her colleagues reported Nov. 23 in Annals of Internal Medicine.

“Given the high cost of DAAs, the medical care required, and the improvements in patient adherence with reductions in treatment duration, attempts to evaluate shorter courses of therapy could have important clinical and public health implications,” Dr. Kohli noted.

Courtesy NIH

Lower baseline HCV viral load, younger age, and HCV genotype 1b were associated with SVR12 with this shortened (vs. the usual 6 weeks) course of direct-acting antiviral (DAA) therapy. Adverse events were mainly mild fatigue, diarrhea, and headaches occurring in 48% and 72% of patients in the 3- and 4-drug regimen groups, respectively, Dr. Kohli said (Ann Intern Med. 2015 Nov. 23[doi:10.7326/M15-0642).

“Sixty-eight percent (34 of 50) of patients had viral relapse, the majority (68%) by posttreatment week 4. Thus, a treatment duration of 4 weeks with 3 or 4 potent DAAs is not sufficient to cure HCV infection in most patients,” she wrote, noting, however, that “some patients are capable of achieving SVR with 4 weeks of therapy, which could be attributable to the presence of several favorable factors, such as early fibrosis, low viral burden, and absence of [resistance-associated variants].

This study was funded in part by the NIH and the German Research Foundation. Study medications were provided by Gilead Sciences. Dr. Kohli reported having no other disclosures. Multiple authors reported other disclosures, including employment and/or stock ownership with Gilead Sciences, research and other funding from Gilead Sciences, and/or stock ownership in Merck, Pfizer, and Johnson & Johnson.

sworcester@frontlinemedcom.com

Shorter-course treatment with combinations of three or four different direct-acting antiviral agents achieved sustain viral response in 12 weeks (SVR12) in less than a third of patients with hepatitis C virus infection in an open-label, non-randomized, phase 2a proof-of-concept study.

SVR12 was achieved in 10 of 25 (40%) treatment-naive patients without cirrhosis who were treated with a 3-drug regimen consisting of ledipasvir and sofosbuvir plus GS-9451 (an NS3/4A protease inhibitor) for 4 weeks, and in 5 of 25 (20%) of 25 treatment-naive patients without cirrhosis treated with ledipasvir and sofosbuvir plus GS9451 and GS-9669 (a nonnucleoside NS5B polymerase inhibitor) for 4 weeks, Dr. Anita Kohli of the National Institutes of Health Clinical Center, Bethesda, Md. and her colleagues reported Nov. 23 in Annals of Internal Medicine.

“Given the high cost of DAAs, the medical care required, and the improvements in patient adherence with reductions in treatment duration, attempts to evaluate shorter courses of therapy could have important clinical and public health implications,” Dr. Kohli noted.

Courtesy NIH

Lower baseline HCV viral load, younger age, and HCV genotype 1b were associated with SVR12 with this shortened (vs. the usual 6 weeks) course of direct-acting antiviral (DAA) therapy. Adverse events were mainly mild fatigue, diarrhea, and headaches occurring in 48% and 72% of patients in the 3- and 4-drug regimen groups, respectively, Dr. Kohli said (Ann Intern Med. 2015 Nov. 23[doi:10.7326/M15-0642).

“Sixty-eight percent (34 of 50) of patients had viral relapse, the majority (68%) by posttreatment week 4. Thus, a treatment duration of 4 weeks with 3 or 4 potent DAAs is not sufficient to cure HCV infection in most patients,” she wrote, noting, however, that “some patients are capable of achieving SVR with 4 weeks of therapy, which could be attributable to the presence of several favorable factors, such as early fibrosis, low viral burden, and absence of [resistance-associated variants].

This study was funded in part by the NIH and the German Research Foundation. Study medications were provided by Gilead Sciences. Dr. Kohli reported having no other disclosures. Multiple authors reported other disclosures, including employment and/or stock ownership with Gilead Sciences, research and other funding from Gilead Sciences, and/or stock ownership in Merck, Pfizer, and Johnson & Johnson.

sworcester@frontlinemedcom.com

Shorter-course treatment with combinations of three or four different direct-acting antiviral agents achieved sustain viral response in 12 weeks (SVR12) in less than a third of patients with hepatitis C virus infection in an open-label, non-randomized, phase 2a proof-of-concept study.

SVR12 was achieved in 10 of 25 (40%) treatment-naive patients without cirrhosis who were treated with a 3-drug regimen consisting of ledipasvir and sofosbuvir plus GS-9451 (an NS3/4A protease inhibitor) for 4 weeks, and in 5 of 25 (20%) of 25 treatment-naive patients without cirrhosis treated with ledipasvir and sofosbuvir plus GS9451 and GS-9669 (a nonnucleoside NS5B polymerase inhibitor) for 4 weeks, Dr. Anita Kohli of the National Institutes of Health Clinical Center, Bethesda, Md. and her colleagues reported Nov. 23 in Annals of Internal Medicine.

“Given the high cost of DAAs, the medical care required, and the improvements in patient adherence with reductions in treatment duration, attempts to evaluate shorter courses of therapy could have important clinical and public health implications,” Dr. Kohli noted.

Courtesy NIH

Lower baseline HCV viral load, younger age, and HCV genotype 1b were associated with SVR12 with this shortened (vs. the usual 6 weeks) course of direct-acting antiviral (DAA) therapy. Adverse events were mainly mild fatigue, diarrhea, and headaches occurring in 48% and 72% of patients in the 3- and 4-drug regimen groups, respectively, Dr. Kohli said (Ann Intern Med. 2015 Nov. 23[doi:10.7326/M15-0642).

“Sixty-eight percent (34 of 50) of patients had viral relapse, the majority (68%) by posttreatment week 4. Thus, a treatment duration of 4 weeks with 3 or 4 potent DAAs is not sufficient to cure HCV infection in most patients,” she wrote, noting, however, that “some patients are capable of achieving SVR with 4 weeks of therapy, which could be attributable to the presence of several favorable factors, such as early fibrosis, low viral burden, and absence of [resistance-associated variants].

This study was funded in part by the NIH and the German Research Foundation. Study medications were provided by Gilead Sciences. Dr. Kohli reported having no other disclosures. Multiple authors reported other disclosures, including employment and/or stock ownership with Gilead Sciences, research and other funding from Gilead Sciences, and/or stock ownership in Merck, Pfizer, and Johnson & Johnson.

sworcester@frontlinemedcom.com

SAN FRANCISCO – The U.S. health care system’s capacity to treat patients who need hepatitis C treatment has improved since 2014, but it still falls far short of what’s needed, according to an analysis presented at the annual meeting of the American Association for the Study of Liver Diseases.

Despite recent improvements, it would still take at least 6 years to treat the majority of patients in need of hepatitis C therapy, explained Jagpreet Chhatwal, Ph.D., of Massachusetts General Hospital, Boston. “Even in the [direct-acting antiviral] era, the burden of hepatitis C remains substantial for a disease for which we have a cure.”

To predict trends in hepatitis C treatment, Dr. Chhatwal and his colleagues developed a mathematical model of health care factors, such as changing treatment regimens, screening policies, and widened insurance coverage.

“We wanted to put all of these different components together to project how the disease burden would change in the near future, and how the disease burden would look if we increased the treatment capacity for hepatitis C,” he said.

In an interview, Dr. Chhatwal discussed his findings and how capacity changes could affect the speed with which those in need receive necessary hepatitis C treatment.

SAN FRANCISCO – The U.S. health care system’s capacity to treat patients who need hepatitis C treatment has improved since 2014, but it still falls far short of what’s needed, according to an analysis presented at the annual meeting of the American Association for the Study of Liver Diseases.

Despite recent improvements, it would still take at least 6 years to treat the majority of patients in need of hepatitis C therapy, explained Jagpreet Chhatwal, Ph.D., of Massachusetts General Hospital, Boston. “Even in the [direct-acting antiviral] era, the burden of hepatitis C remains substantial for a disease for which we have a cure.”

To predict trends in hepatitis C treatment, Dr. Chhatwal and his colleagues developed a mathematical model of health care factors, such as changing treatment regimens, screening policies, and widened insurance coverage.

“We wanted to put all of these different components together to project how the disease burden would change in the near future, and how the disease burden would look if we increased the treatment capacity for hepatitis C,” he said.

In an interview, Dr. Chhatwal discussed his findings and how capacity changes could affect the speed with which those in need receive necessary hepatitis C treatment.

SAN FRANCISCO – The U.S. health care system’s capacity to treat patients who need hepatitis C treatment has improved since 2014, but it still falls far short of what’s needed, according to an analysis presented at the annual meeting of the American Association for the Study of Liver Diseases.

Despite recent improvements, it would still take at least 6 years to treat the majority of patients in need of hepatitis C therapy, explained Jagpreet Chhatwal, Ph.D., of Massachusetts General Hospital, Boston. “Even in the [direct-acting antiviral] era, the burden of hepatitis C remains substantial for a disease for which we have a cure.”

To predict trends in hepatitis C treatment, Dr. Chhatwal and his colleagues developed a mathematical model of health care factors, such as changing treatment regimens, screening policies, and widened insurance coverage.

“We wanted to put all of these different components together to project how the disease burden would change in the near future, and how the disease burden would look if we increased the treatment capacity for hepatitis C,” he said.

In an interview, Dr. Chhatwal discussed his findings and how capacity changes could affect the speed with which those in need receive necessary hepatitis C treatment.

SAN FRANCISCO – Response-guided therapy using all-oral, triple direct-acting antiviral (DAA) therapy appears useful for shortening the duration of treatment in noncirrhotic patients with hepatitis C virus genotype 1b infection, according to findings from the randomized proof-of-concept SODAPI study.

The findings of the open-label study strongly suggest that administration of potent triple regimens containing NS3, NS5A, and NS5B HCV inhibitors leads to rapid virologic response within 2 days in a majority of treated patients, Dr. George K. Lau of Emory University, Atlanta, reported at the annual meeting of the American Association for the Study of Liver Diseases.

Courtesy US. Dept of Veterans Affairs

Study subjects were 26 Chinese patients who received either sofosbuvir, ledipasvir, and asunaprevir (group 1, 12 patients); sofosbuvir, daclatasvir, and simeprevir (group 2, 6 patients); or sofosbuvir, daclatasvir, and asunaprevir (group 3, 8 patients) at approved doses. Those who achieved rapid virologic response remained on the regimen for 3 weeks; those who did not were treated for 8-12 weeks.

Rapid virologic response was achieved by 6 of 12 group 1 patients, 6 of 6 group 2 patients, and 6 of 8 group 3 patients. Baseline viral load was lower in those with rapid virologic response vs. those without (5.96 vs. 7.00 log₁₀ IU/mL), Dr. Lau noted.

All 18 subjects with rapid virologic response and 3 weeks of treatment achieved the primary endpoint of plasma HCV RNA below the detectable limit at 12 weeks (SVR12). Median time to plasma HCV RNA less than 25 IU/mL was shortest in group 1 vs. group 3, he said.

Treatment was well tolerated; no patients discontinued therapy and no significant adverse events were reported.

Patients in the study were noncirrhotic patients with chronic hepatitis C genotype 1b infection with a median age of 34 years, median body mass index of 21.7 kg/m², and baseline mean HCV RNA of 6.55 log₁₀ IU/mL. Six were men, 12 were women.

DAAs have a high cure rate and favorable tolerability in persons infected with hepatitis C virus, but shorter courses could improve adherence and affordability and could increase accessibility to DAAs, Dr. Lau said.

He and his colleagues “postulated that the addition of an NS3 protease inhibitor to dual NS5A-NS5B (nucleoside) inhibitors would enhance antiviral efficacy and reduce treatment duration to 3 weeks in those with a rapid virologic response defined as plasma HCV RNA less than 500 IU/mL by day 2.”

Based on these positive early findings, future studies exploring this response-guided approach to therapy are recommended, as this approach has the potential to reduce therapy duration and drug costs, and to improve accessibility and adherence, he concluded.

Dr. Lau is a consultant for Roche and Novartis.

sworcester@frontlinemedcom.com

SAN FRANCISCO – Response-guided therapy using all-oral, triple direct-acting antiviral (DAA) therapy appears useful for shortening the duration of treatment in noncirrhotic patients with hepatitis C virus genotype 1b infection, according to findings from the randomized proof-of-concept SODAPI study.

The findings of the open-label study strongly suggest that administration of potent triple regimens containing NS3, NS5A, and NS5B HCV inhibitors leads to rapid virologic response within 2 days in a majority of treated patients, Dr. George K. Lau of Emory University, Atlanta, reported at the annual meeting of the American Association for the Study of Liver Diseases.

Courtesy US. Dept of Veterans Affairs

Study subjects were 26 Chinese patients who received either sofosbuvir, ledipasvir, and asunaprevir (group 1, 12 patients); sofosbuvir, daclatasvir, and simeprevir (group 2, 6 patients); or sofosbuvir, daclatasvir, and asunaprevir (group 3, 8 patients) at approved doses. Those who achieved rapid virologic response remained on the regimen for 3 weeks; those who did not were treated for 8-12 weeks.

Rapid virologic response was achieved by 6 of 12 group 1 patients, 6 of 6 group 2 patients, and 6 of 8 group 3 patients. Baseline viral load was lower in those with rapid virologic response vs. those without (5.96 vs. 7.00 log₁₀ IU/mL), Dr. Lau noted.

All 18 subjects with rapid virologic response and 3 weeks of treatment achieved the primary endpoint of plasma HCV RNA below the detectable limit at 12 weeks (SVR12). Median time to plasma HCV RNA less than 25 IU/mL was shortest in group 1 vs. group 3, he said.

Treatment was well tolerated; no patients discontinued therapy and no significant adverse events were reported.

Patients in the study were noncirrhotic patients with chronic hepatitis C genotype 1b infection with a median age of 34 years, median body mass index of 21.7 kg/m², and baseline mean HCV RNA of 6.55 log₁₀ IU/mL. Six were men, 12 were women.

DAAs have a high cure rate and favorable tolerability in persons infected with hepatitis C virus, but shorter courses could improve adherence and affordability and could increase accessibility to DAAs, Dr. Lau said.

He and his colleagues “postulated that the addition of an NS3 protease inhibitor to dual NS5A-NS5B (nucleoside) inhibitors would enhance antiviral efficacy and reduce treatment duration to 3 weeks in those with a rapid virologic response defined as plasma HCV RNA less than 500 IU/mL by day 2.”

Based on these positive early findings, future studies exploring this response-guided approach to therapy are recommended, as this approach has the potential to reduce therapy duration and drug costs, and to improve accessibility and adherence, he concluded.

Dr. Lau is a consultant for Roche and Novartis.

sworcester@frontlinemedcom.com

SAN FRANCISCO – Response-guided therapy using all-oral, triple direct-acting antiviral (DAA) therapy appears useful for shortening the duration of treatment in noncirrhotic patients with hepatitis C virus genotype 1b infection, according to findings from the randomized proof-of-concept SODAPI study.

The findings of the open-label study strongly suggest that administration of potent triple regimens containing NS3, NS5A, and NS5B HCV inhibitors leads to rapid virologic response within 2 days in a majority of treated patients, Dr. George K. Lau of Emory University, Atlanta, reported at the annual meeting of the American Association for the Study of Liver Diseases.

Courtesy US. Dept of Veterans Affairs

Study subjects were 26 Chinese patients who received either sofosbuvir, ledipasvir, and asunaprevir (group 1, 12 patients); sofosbuvir, daclatasvir, and simeprevir (group 2, 6 patients); or sofosbuvir, daclatasvir, and asunaprevir (group 3, 8 patients) at approved doses. Those who achieved rapid virologic response remained on the regimen for 3 weeks; those who did not were treated for 8-12 weeks.

Rapid virologic response was achieved by 6 of 12 group 1 patients, 6 of 6 group 2 patients, and 6 of 8 group 3 patients. Baseline viral load was lower in those with rapid virologic response vs. those without (5.96 vs. 7.00 log₁₀ IU/mL), Dr. Lau noted.

All 18 subjects with rapid virologic response and 3 weeks of treatment achieved the primary endpoint of plasma HCV RNA below the detectable limit at 12 weeks (SVR12). Median time to plasma HCV RNA less than 25 IU/mL was shortest in group 1 vs. group 3, he said.

Treatment was well tolerated; no patients discontinued therapy and no significant adverse events were reported.

Patients in the study were noncirrhotic patients with chronic hepatitis C genotype 1b infection with a median age of 34 years, median body mass index of 21.7 kg/m², and baseline mean HCV RNA of 6.55 log₁₀ IU/mL. Six were men, 12 were women.

DAAs have a high cure rate and favorable tolerability in persons infected with hepatitis C virus, but shorter courses could improve adherence and affordability and could increase accessibility to DAAs, Dr. Lau said.

He and his colleagues “postulated that the addition of an NS3 protease inhibitor to dual NS5A-NS5B (nucleoside) inhibitors would enhance antiviral efficacy and reduce treatment duration to 3 weeks in those with a rapid virologic response defined as plasma HCV RNA less than 500 IU/mL by day 2.”

Based on these positive early findings, future studies exploring this response-guided approach to therapy are recommended, as this approach has the potential to reduce therapy duration and drug costs, and to improve accessibility and adherence, he concluded.

Dr. Lau is a consultant for Roche and Novartis.

sworcester@frontlinemedcom.com

SAN FRANCISCO – Can patients who fail short-course treatment for hepatitis C and show high levels of resistance to an antiviral drug still respond to standard 12-week therapy?

“There were initially some data that retreatment might not be as good,” explained Dr. Eleanor Wilson of the University of Maryland, Baltimore.

In the SYNERGY trial, patients underwent short-course therapy with three or four directly acting antivirals. Those who failed the short-course therapies had the opportunity to re-enroll for 12-week standard-of-care therapy. Dr. Wilson and her colleagues studied patients who failed short-course therapy but then underwent 12-week HCV treatment.

In an interview at the annual meeting of the American Association for the Study of Liver Diseases, Dr. Wilson discussed her findings and whether retreatment for 12 weeks was effective, particularly in patients with high levels of resistance to ledipasvir.

SAN FRANCISCO – Can patients who fail short-course treatment for hepatitis C and show high levels of resistance to an antiviral drug still respond to standard 12-week therapy?

“There were initially some data that retreatment might not be as good,” explained Dr. Eleanor Wilson of the University of Maryland, Baltimore.

In the SYNERGY trial, patients underwent short-course therapy with three or four directly acting antivirals. Those who failed the short-course therapies had the opportunity to re-enroll for 12-week standard-of-care therapy. Dr. Wilson and her colleagues studied patients who failed short-course therapy but then underwent 12-week HCV treatment.

In an interview at the annual meeting of the American Association for the Study of Liver Diseases, Dr. Wilson discussed her findings and whether retreatment for 12 weeks was effective, particularly in patients with high levels of resistance to ledipasvir.

SAN FRANCISCO – Can patients who fail short-course treatment for hepatitis C and show high levels of resistance to an antiviral drug still respond to standard 12-week therapy?

“There were initially some data that retreatment might not be as good,” explained Dr. Eleanor Wilson of the University of Maryland, Baltimore.

In the SYNERGY trial, patients underwent short-course therapy with three or four directly acting antivirals. Those who failed the short-course therapies had the opportunity to re-enroll for 12-week standard-of-care therapy. Dr. Wilson and her colleagues studied patients who failed short-course therapy but then underwent 12-week HCV treatment.

In an interview at the annual meeting of the American Association for the Study of Liver Diseases, Dr. Wilson discussed her findings and whether retreatment for 12 weeks was effective, particularly in patients with high levels of resistance to ledipasvir.