Still a brilliant victory in the battle of the drug against the hepatitis C liver damaging virus (HCV) may be on the horizon: A small study suggests it may be possible to cure some people of their infection in as little as three weeks.
fresh on the heels of recent approvals of four new combinations of HCV drugs that clear infection from many different types of viruses in about 3 months, a team led by George Lau hepatologist humanity and healthy GI and liver Centre in Hong Kong, China, has mixed and matched various compounds to see if they could still shorten the road to recovery. After 3 weeks of treatment, 18 HCV-infected persons given three different drug combinations met the standard definition being cured at 12 weeks after starting treatment, they had no signs of genetic material of HCV RNA in their blood on standard tests. The researchers plan to present these data to the public for the first time at a scientific conference known as The Liver Meeting in 2 weeks.
Until new drugs for HCV have appeared, infected people needing treatment for 8 months, as well as therapies often fail and had serious side effects. Now the standard treatment protocol calls for HCV drugs taken for only 12 weeks. Cut that time even more dramatic treatment is "really, really fascinating," said Shyam Kottilil, an HCV researcher at the Institute of Human Virology in Baltimore, Maryland. And if the results are valid, it could reduce the cost global processing $ 100,000 required by the most popular drugs used for the treatment of 12 weeks. Kottilil own study of a treatment four weeks tested different drug combinations on a single a different rate of population patients were 40% healing in 50 participants. (This study is in press in Annals of Internal Medicine.)
other researchers point out several warnings to the success of three weeks including the 18 people treated had several characteristics of patients who respond well to HCV drugs. "It is very interesting, but not unexpected," said David Nelson, a researcher of hepatitis at the University of Florida in Gainesville.
Raymond Schinazi, a biochemist at Emory University in Atlanta, who worked with Lau, recognizes that this is only a pilot study and needs confirmation in a larger clinical trial. "But when you get 100%, it is still statistically significant," said Schinazi, who helped develop a new blockbuster drugs HCV sofosbuvir, which was part of the combinations tried in the new study.
the rapid clearance of HCV from the body seen in the study upends mechanistic models of how the treatment heals people with HCV. "Our models do not predict at all," said another employee, Alan Perelson, a biophysicist Los Alamos National laboratory in New Mexico, which has an essential work on how the treatment led to the clearance of HCV and HIV. "There is a piece of basic science on viral clearance we are still missing. "
Until May 2011, the only drugs approved to treat HCV worked by non-specific disorders and antiviral and immune mechanisms, have significant side effects, and 40% of the time. Since then, a dozen so-called antivirals direct action came on the market, all of which are expensive and many alike, promising candidates are in development.
The study of Hong Kong tested three different triple combinations of antivirals most effective direct action, each of the houses on different HCV enzymes or proteins important for replication. Sofosbuvir-created by a small biotech Schinazi began which was acquired by Gilead Sciences of Foster City, HCV polymerase California target RNA and was the backbone of all three regimes. Widely regarded as the "first in class" in the world of HCV drugs, sofosbuvir has a relatively high power, causes few side effects, and is rarely thwarted by drug resistance mutations. (Its selling price initial retail, $ 1000 per pill, sparked an international controversy.) the researchers combined with either ledipasvir or Daclatasvir, paralyzing a viral protein known as NS5a. To finish the cocktail, the researchers added one of two inhibitors of HCV protease, Simeprevir or Asunaprevir.
Three different companies Big Pharma are various medications, and Schinazi says that to protect their markets, they resisted to collaborate with each other. "I want to show these companies they should have done this long ago study themselves, "said Schinazi, which helped pay for the drugs used in the study." When you put together the best drugs, you get fabulous results . "
to achieve these results, the researchers deliberately have the lowest hanging fruit and Hong Kong was an ideal test site. HCV has six genotypes which are, in turn, are divided into subtypes. In China, the most common is the genotype 1b, responding more readily to drug treatment than any other genotype: Previous studies have shown that 8 weeks of sofosbuvir ledipasvir and can cure almost everyone. Large studies have also found that 84% of patients with HCV Chinese have a variation of an immune gene (technically known as IL28B cc ) which leads to a strong natural attack against the virus in giving them an advantage when treated with effective drugs. "So you're looking at [a] population that has not only the best genotype, but the host may play a role," says Mark Sulkowski, director of the center of viral hepatitis at the Johns Hopkins University School of Medicine in Baltimore, Maryland.
investigators stacked the deck in two other ways. As is commonly done in clinical trials of HCV drugs, they excluded people infected with HCV who underwent liver cirrhosis and therefore are more difficult to cure. in addition, the study used an unusual guided study model called response therapy. a total of 26 persons started treatment and the researchers checked their blood levels of HCV after 2 days the selection of 18 people who had larger viral load decreases to the short duration of therapy and treatment of other standards for 12 weeks. These 18 participants were also lower HCV viral loads pre-treatment.
The University of David Nelson of Florida said the study "is a great proof of concept", but wondered how applicable the 3-week treatment system will be in the global response. Although the genotype 1 accounts for approximately 46% of all infections worldwide, the majority of Americans subtype 1a-more difficult to treat. about 22% of people have the genotype 3, which is similar more difficult to cure as 1b. Ideally, said Nelson, a standard treatment protocol should work against all genotypes without the need to test the initial responses and whatever the status of cirrhosis.
Although Sulkowski accept that treatment ultrashort will not be a single one-size everything, he replies that it can be pragmatic in certain contexts. "This study really opens up a philosophical discussion on how to treat hepatitis C," says Sulkowski. "Maybe it there is a role for a complicated strategy that shortens the therapy. "in the US, for example, it may make economic sense in some health care systems to pay extra to test genotype 1b patients-representing 25 % of the population infected two days in therapy and selecting speakers for the treatment course of 3 weeks. Consider that nearly 180,000 people who receive care from the Veterans Health Administration have tested positive for HCV: According to estimates, it would cost $ 12 billion to treat everyone for 12 weeks, even the greatly reduced in rate for drugs. Shaving 9 weeks for thousands of people could equal huge savings in drug costs.
Sulkowski said although the ultrashort therapy regimen does not have a cure rate of 100%, it may not pose great risks for patients. As he and others reveal at the liver meeting a growing body of evidence shows that patients who fail to treatment often respond if treated again with different drugs. "If I tell a patient, I'll treat you for 4 weeks and if you do not answer, I can save you with another approach, which is a reasonable strategy for a country like the United States"
Schinazi said combinations of more powerful drugs and higher doses of existing ones could reduce the time to heal further. "I think eventually we could go to 2 weeks," he said.
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