Laurie Barclay, MD
September 24, 2010 — Weight-based taribavirin (TBV) treatment was associated with a reduction in anemia and increased sustained virologic response in treatment-naive patients with genotype 1 chronic hepatitis C virus (HCV) infection, according to the results of a phase 2b, open-label, active-controlled, parallel-group, randomized study published online June 30 and in the October issue of Hepatology.
"Ribavirin [RBV]-induced hemolytic anemia can prompt dose reductions and lower sustained virologic response (SVR) rates in the treatment of patients with chronic hepatitis C," write Fred Poordad, MD, from Cedars-Sinai Medical Center in Los Angeles, California, and colleagues. "The study aimed to determine if weight-based dosing of [TBV], an oral prodrug of [RBV], demonstrated efficacy comparable to RBV while maintaining its previously demonstrated anemia advantage with fixed dose administration."
At 51 centers in the United States between March 2007 and October 2008, 278 treatment-naive patients infected with genotype 1 HCV were stratified by body weight and baseline viral load and randomly assigned 1:1:1:1 to receive TBV (20, 25, or 30 mg/kg/day) or RBV (800 - 1400 mg/day) with pegylated interferon alfa-2b for 48 weeks.
"This study suggests that comparable SVR rates may be achieved with weight based taribavirin and peg interferon in a genotype 1 population," Paul Y. Kwo, MD, associate professor of medicine, Division of Gastroenterology/Hepatology, Indiana University School of Medicine in Indianapolis, and coauthor of an accompanying editorial, published online September 7 and in the October issue of the journal, told Medscape Medical News. "Thus, as we enter the era of direct-acting antiviral agents (DAAs) with PEG interferon and RBV, TBV is an agent that deserves study to see if it can be added to PEG interferon and DAAs to preserve or improve SVR rates with lower rates of anemia. "
This patient population used in this study was considered difficult to cure because of their demographics and clinical characteristics, including high viral load and advanced fibrosis. Mean age was 49 years, 61% were men, 30% were black or Latino, and mean weight was 82 kg.
SVR rates were 28.4%, 24.3%, 20.6%, and 21.4% in the 20-, 25-, and 30-mg/kg TBV groups and the RBV group, respectively. Efficacy analyses showed no statistical differences.
Compared with the RBV groups, the 20- and 25-mg/kg/day TBV treatment groups had significantly lower rates of anemia (32.9%, 13.4%, and 15.7%, respectively; P < .05). In all groups, the most commonly reported adverse events were fatigue, diarrhea, and insomnia. Although diarrhea was reported in 38% of patients receiving TBV compared with 21% of patients receiving RBV, this was generally mild and not dose-limiting.
Fewer patients treated with TBV required dose reductions (13% - 28%) compared with 32% of patients treated with RBV. Less-frequent dose modification in patients treated with TBV may reduce the requirement for use of erythropoiesis-stimulating agents.
"All TBV doses demonstrated efficacy and tolerability comparable to that of RBV; however, the 25 mg/kg dose demonstrated the optimal balance of safety and efficacy," the study authors write. "Anemia rates were significantly lower for TBV given at 20-25 mg/kg than RBV. These data suggest weight-based dosing with TBV provides a safe and effective treatment alternative to RBV for chronic [HCV]."
When asked about study limitations, Dr. Kwo noted that despite the lower anemia rates, the drop-out rate for anemia was similar between TBV and RBV, possibly because of a small sample size.
"There are many populations that have great difficulty tolerating RBV now (those with advanced liver disease, older patients, patients who have undergone liver transplantation, human immunodeficiency virus/HCV-coinfected individuals, and patients with hemoglobulinopathies and chronic renal failure), and these are populations that could potentially benefit from TBV," Dr. Kwo concluded. "[In future studies], TBV should be added to PEG interferon and DAA agents to see if viral response rates can be preserved or improved with lower rates of anemia when compared to PEG interferon, RBV and DAA agents."
Valeant Pharmaceuticals employs 4 of the study authors. The other study authors have disclosed no relevant financial relationships. Dr. Kwo reports receiving grant support from Schering Plough, Merck, Vertex, Valeant, Abbott, Bristol Myers Squibb, Tibotec, Glaxo Smith Kline, and Gilead; consulting for Schering Plough/Merck, Idenix, and Human Genome Sciences; and consulting on the ad boards for Merck, Schering Plough, Vertex, Gilead, Anadys, Abbott, Human Genome Sciences, and Novartis. He also reports speaking and teaching for Schering Plough/Merck, Roche, Gilead, and Bristol-Myers Squibb.
Hepatology. Published online June 30 and September 7, 2010.
Source
Also See:
-- Weight-Based Dosing Best for New HCV Drug
-- Taribavirin Offers a Safe, Effective Alternative for Chronic Hepatitis C, Study Finds
September 24, 2010
Liver Cancer and Hep C Patients
By: Monica Smith
Friday, September 24 2010
(HealthDay News) — People with elevated hepatitis C virus (HCV) RNA and ALT levels and HCV genotype 1 appear to be at increased risk for developing hepatocellular carcinoma, according to research published online Sept. 20 in the Journal of Clinical Oncology.
Mei-Hsuan Lee, of the National Taiwan University, and colleagues assessed serum HCV RNA and ALT levels and HCV genotypes in 925 subjects positive for HCV antibodies who were followed from 1991 to 2006. Their objective was to determine those three factors' predictability of hepatocellular carcinoma risk.
During follow-up, 55 subjects developed hepatocellular carcinoma. The researchers found that risk increased from 1.1 percent in those with HCV RNA seronegative status to 6.4 percent for subjects with low HCV RNA levels and 14.7 percent for those with high HCV RNA levels. Elevated serum ALT levels were also associated with increased cumulative risk, and presence of HCV genotype 1 was associated with a higher risk than not having that genotype (12.6 versus 4.5 percent).
"Elevated serum levels of HCV RNA and ALT and HCV genotype 1 infection are independent risk predictors of hepatocellular carcinoma. These findings have strong implications for the management of chronic HCV," the authors write.
The research was supported in part by Bristol-Myers Squibb.
Abstract
Full Text (subscription or payment may be required)
Source
Friday, September 24 2010
(HealthDay News) — People with elevated hepatitis C virus (HCV) RNA and ALT levels and HCV genotype 1 appear to be at increased risk for developing hepatocellular carcinoma, according to research published online Sept. 20 in the Journal of Clinical Oncology.
Mei-Hsuan Lee, of the National Taiwan University, and colleagues assessed serum HCV RNA and ALT levels and HCV genotypes in 925 subjects positive for HCV antibodies who were followed from 1991 to 2006. Their objective was to determine those three factors' predictability of hepatocellular carcinoma risk.
During follow-up, 55 subjects developed hepatocellular carcinoma. The researchers found that risk increased from 1.1 percent in those with HCV RNA seronegative status to 6.4 percent for subjects with low HCV RNA levels and 14.7 percent for those with high HCV RNA levels. Elevated serum ALT levels were also associated with increased cumulative risk, and presence of HCV genotype 1 was associated with a higher risk than not having that genotype (12.6 versus 4.5 percent).
"Elevated serum levels of HCV RNA and ALT and HCV genotype 1 infection are independent risk predictors of hepatocellular carcinoma. These findings have strong implications for the management of chronic HCV," the authors write.
The research was supported in part by Bristol-Myers Squibb.
Abstract
Full Text (subscription or payment may be required)
Source
Did doctors jumpstart the HIV pandemic?
Thu, Sep 23 2010
By Frederik Joelving
NEW YORK (Reuters Health) - Perhaps it wasn't sex workers and fast-growing cities that launched HIV onto its deadly global rampage, but well-meaning doctors using dirty needles in the first half of the 20th century.
While it's hard to know for sure today, more than 90 years after the virus emerged, two new studies hint that campaigns to eradicate tropical diseases in Africa might have helped HIV gain an early foothold among humans.
"This is sort of an example of good intentions gone wrong," said Dr. Thomas Strickland, an expert in infectious diseases at Baltimore's University of Maryland, who was not involved in the research.
"They were saving lives. They just didn't know that they were also setting up the pandemic of HIV."
The virus jumped from chimps to humans -- morphing from simian immunodeficiency virus, or SIV, to human immunodeficiency virus -- in central Africa in the early 1920s.
Most likely, scientists speculate, a hunter got infected through a bite or a scratch as he prowled for bush meat and butchered it west of the Ubangi River in what is now the Democratic Republic of the Congo.
What is still a matter of debate is how a blood-borne disease infecting one or a few individuals in a remote area could ever spread to the more than 33 million people who were infected by 2008, and kill two million of them.
To try to answer that question, Dr. Jacques Pepin, of the Universite de Sherbrooke in Montreal, Canada, hopped on a plane to central Africa. His goal was to track the spread of less lethal viruses -- as proxies for HIV -- among villagers who remembered the colonial era.
For one of two studies published this month, Pepin's team knocked on doors in dozens of villages in the Central African Republic to find seniors who'd been exposed to the sleeping sickness epidemic that ravaged the area between 1936 and 1950.
They asked a bunch of questions of more than 900 villagers, including whether or not they'd been treated for sleeping sickness -- at the time a grueling, hard-to-forget series of injections, Pepin said.
The researchers also took blood samples. Because the villagers who first caught HIV would be long dead today, Pepin decided to use the less-deadly hepatitis C virus as well as another blood-borne virus (human T cell lymphotropic virus 1, or HTLV-1) as models for how HIV could have been inadvertently transmitted by the French colonial doctors treating sleeping sickness.
What they found was striking: if a person had been treated for the sleeping disease before 1951, the chances that he or she had been infected with hepatitis C tripled. And HTLV-1 showed a similar pattern.
"What happened is that for a long time, the needles and syringes used to administer the intravenous drugs were not single-use," Pepin told Reuters Health. "There were a lot of patients and not a lot of needles, so the sterilization of needles was not very efficient."
"If HIV was present in one of these patients 50 years ago, we can assume that they probably transmitted HIV," he said. "It is exactly like intravenous drug users who share needles."
According to Pepin, that would also explain why the number of people 65 years and older who'd been treated for sleeping sickness was six times lower than would be expected from historical data: the missing seniors could have died of AIDS, the immune system breakdown caused by HIV.
"Everybody now is getting infected from having sex," said Strickland, who wrote an editorial about the new findings, published in the journal Clinical Infectious Diseases.
"But that is not very good transmission. You can have heterosexual sex ten or fifteen times without getting infected. But if you get injected with a contaminated needle, the risk is much higher."
Pepin's other study shows that in Cameroon, a neighboring state that also used to be under French rule, massive outbreaks of hepatitis C in the first half of the 19th century were related to malaria treatment with the drug quinine.
More than half the hundreds of graying heads he rounded up had traces of an earlier hepatitis C infection in their blood.
"The most important mode of infection was the intravenous treatment of malaria," said Pepin. "If we put all of this together, it shows that there was a lot of transmission of different viruses through different interventions for tropical diseases."
"Probably HIV was transmitted as well," he argues.
But nobody is left to bear witness of what really happened, and not all scientists believe Pepin's explanation.
"It is a wonderful study on the hepatitis C virus," said Michael Worobey, a biologist at the University of Arizona in Tucson who studies the origins of HIV. "I'm not so convinced it should have been sold on the HIV/SIV angle."
His version of what happened follows the traditional line of argument among scientists: as colonial powers began building cities and railroads, they transformed former woodlands into densely populated towns rife with prostitution -- perfect hotbeds for blood-borne diseases.
Eventually an infected villager made his way to the city, setting off the HIV epidemic like a spark falling on a dry savanna.
"I think a train is a much better way to get a virus to a city than a needle," Worobey told Reuters Health.
He said the idea that doctors kicked off the HIV pandemic has been around for years. And while the new experiments are probably the first to test it, he added, they don't settle the question.
To Pepin, the two explanations aren't mutually exclusive. Dirty needles "played a substantial role that was probably as important as prostitution," he said.
Although single-use needles are now commonplace in most of the world, and unprotected sex is the major reason people get HIV, Pepin said some wisdom might still be gleaned from what he found.
"Hopefully it will make doctors a bit more prudent about novel medical interventions," he said.
Source
By Frederik Joelving
NEW YORK (Reuters Health) - Perhaps it wasn't sex workers and fast-growing cities that launched HIV onto its deadly global rampage, but well-meaning doctors using dirty needles in the first half of the 20th century.
While it's hard to know for sure today, more than 90 years after the virus emerged, two new studies hint that campaigns to eradicate tropical diseases in Africa might have helped HIV gain an early foothold among humans.
"This is sort of an example of good intentions gone wrong," said Dr. Thomas Strickland, an expert in infectious diseases at Baltimore's University of Maryland, who was not involved in the research.
"They were saving lives. They just didn't know that they were also setting up the pandemic of HIV."
The virus jumped from chimps to humans -- morphing from simian immunodeficiency virus, or SIV, to human immunodeficiency virus -- in central Africa in the early 1920s.
Most likely, scientists speculate, a hunter got infected through a bite or a scratch as he prowled for bush meat and butchered it west of the Ubangi River in what is now the Democratic Republic of the Congo.
What is still a matter of debate is how a blood-borne disease infecting one or a few individuals in a remote area could ever spread to the more than 33 million people who were infected by 2008, and kill two million of them.
To try to answer that question, Dr. Jacques Pepin, of the Universite de Sherbrooke in Montreal, Canada, hopped on a plane to central Africa. His goal was to track the spread of less lethal viruses -- as proxies for HIV -- among villagers who remembered the colonial era.
For one of two studies published this month, Pepin's team knocked on doors in dozens of villages in the Central African Republic to find seniors who'd been exposed to the sleeping sickness epidemic that ravaged the area between 1936 and 1950.
They asked a bunch of questions of more than 900 villagers, including whether or not they'd been treated for sleeping sickness -- at the time a grueling, hard-to-forget series of injections, Pepin said.
The researchers also took blood samples. Because the villagers who first caught HIV would be long dead today, Pepin decided to use the less-deadly hepatitis C virus as well as another blood-borne virus (human T cell lymphotropic virus 1, or HTLV-1) as models for how HIV could have been inadvertently transmitted by the French colonial doctors treating sleeping sickness.
What they found was striking: if a person had been treated for the sleeping disease before 1951, the chances that he or she had been infected with hepatitis C tripled. And HTLV-1 showed a similar pattern.
"What happened is that for a long time, the needles and syringes used to administer the intravenous drugs were not single-use," Pepin told Reuters Health. "There were a lot of patients and not a lot of needles, so the sterilization of needles was not very efficient."
"If HIV was present in one of these patients 50 years ago, we can assume that they probably transmitted HIV," he said. "It is exactly like intravenous drug users who share needles."
According to Pepin, that would also explain why the number of people 65 years and older who'd been treated for sleeping sickness was six times lower than would be expected from historical data: the missing seniors could have died of AIDS, the immune system breakdown caused by HIV.
"Everybody now is getting infected from having sex," said Strickland, who wrote an editorial about the new findings, published in the journal Clinical Infectious Diseases.
"But that is not very good transmission. You can have heterosexual sex ten or fifteen times without getting infected. But if you get injected with a contaminated needle, the risk is much higher."
Pepin's other study shows that in Cameroon, a neighboring state that also used to be under French rule, massive outbreaks of hepatitis C in the first half of the 19th century were related to malaria treatment with the drug quinine.
More than half the hundreds of graying heads he rounded up had traces of an earlier hepatitis C infection in their blood.
"The most important mode of infection was the intravenous treatment of malaria," said Pepin. "If we put all of this together, it shows that there was a lot of transmission of different viruses through different interventions for tropical diseases."
"Probably HIV was transmitted as well," he argues.
But nobody is left to bear witness of what really happened, and not all scientists believe Pepin's explanation.
"It is a wonderful study on the hepatitis C virus," said Michael Worobey, a biologist at the University of Arizona in Tucson who studies the origins of HIV. "I'm not so convinced it should have been sold on the HIV/SIV angle."
His version of what happened follows the traditional line of argument among scientists: as colonial powers began building cities and railroads, they transformed former woodlands into densely populated towns rife with prostitution -- perfect hotbeds for blood-borne diseases.
Eventually an infected villager made his way to the city, setting off the HIV epidemic like a spark falling on a dry savanna.
"I think a train is a much better way to get a virus to a city than a needle," Worobey told Reuters Health.
He said the idea that doctors kicked off the HIV pandemic has been around for years. And while the new experiments are probably the first to test it, he added, they don't settle the question.
To Pepin, the two explanations aren't mutually exclusive. Dirty needles "played a substantial role that was probably as important as prostitution," he said.
Although single-use needles are now commonplace in most of the world, and unprotected sex is the major reason people get HIV, Pepin said some wisdom might still be gleaned from what he found.
"Hopefully it will make doctors a bit more prudent about novel medical interventions," he said.
Source
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