Navigation Links
Widely used hepatitis B drug spurs HIV drug resistance

A Johns Hopkins study has proven false established medical practice that an antiretroviral drug widely used to treat hepatitis B liver infections was safe to use on its own in patients co-infected with HIV. Their findings demonstrate that treatment with entecavir leads to cross-resistance to other antiviral drugs used to treat the AIDS virus.

"Our results show that entecavir is no different from any other that has been shown to be active against HIV - it breeds resistance rapidly, despite its ability to reduce the amount of HIV in the body," says senior study author and infectious disease specialist Chloe Thio, M.D.

Researchers say the findings, to be presented Feb. 28 at the 2007 Conference on Retroviruses and Opportunistic Infections (CROI) in Los Angeles, have serious implications for the more than 4 million people worldwide believed to be infected with both viral illnesses but who need to treat their hepatitis B and are not yet on anti-HIV drugs.

Authors of the study have informed the U.S. Food and Drug Administration of their results so that prescribing physicians can be notified and so that drug labeling can be changed. They have also notified Bristol-Myers Squibb, which makes and sells entecavir under the brand name Baraclude.

"The alert should go out to co-infected people to consult with their physicians immediately about entecavir to see if it is the right drug to treat their hepatitis B in the first place and to evaluate alternative therapies," says Thio, an associate professor of medicine at The Johns Hopkins University School of Medicine.

Thio says she has stopped prescribing entecavir as her first option in treating hepatitis B in co-infected patients who are not already using drugs to suppress HIV.

"The good news is that co-infected patients already on HIV therapy can still use entecavir to treat their hepatitis B, but the bad news is that there are now fewer options for treating hepatitis B first," she adds. Hepatitis B infection attacks the liver and can lead to cirrhosis, liver cancer or even death from liver failure.

Entecavir, first marketed in March 2005, has been a leading treatment for chronic forms of hepatitis B, which can be fatal to almost a quarter of those infected if it is left untreated. The drug's label information currently states that is has no clinical effects on HIV.

According to Thio, some co-infected patients decide first to treat their hepatitis B infection if HIV has not yet weakened their immune system and to avoid the debilitating side effects of anti-HIV medications.

In the Hopkins study, researchers found in both laboratory and clinical tests that within six months of entecavir therapy, a so-called M184V mutation of HIV develops. Thio says viruses with this mutation are known to be resistant to lamivudine, better known as 3TC, a medication that prevents HIV replication and "is a cornerstone of most drug-combination therapies used to fight the immune system disease." Because lamivudine is in the same category of HIV therapies as another widely used drug, emtricitabine, its effectiveness is also compromised by entecavir, she says.

Thio began to investigate entecavir's effects on HIV in fall 2006 after noticing reports of anti-HIV activity in two co-infected patients, one at the Johns Hopkins Moore Clinic, which specializes in HIV/AIDS care, and another at a San Diego medical center. The patients (and there is now a third case) were taking only entecavir yet showed a tenfold decrease in the amount of HIV in their blood.

Previous studies had shown entecavir not to have any significant effects on HIV, about they were based on older tests that could not quantify the effects of HIV on individual immune cells or detect mutations. Thio believed that the recent patient cases called for a more thorough investigation with more advanced techniques.

She and her team c ombined various concentrations of entecavir with 100,000 human immune cells from a healthy blood donor, then infected them with an HIV test virus and measured the number of cells infected over time.

The lab test, developed at Hopkins by study co-author Robert Siliciano, M.D., Ph.D., a professor at Hopkins and a Howard Hughes Medical Institute investigator, specifically tests what drugs affect HIV and can be tailored to probe effects on any particular mutant of HIV.

Lab results showed that entecavir, in concentrations less than a tenth of what is used in humans, cut the number of newly infected cells in half. However, at increasing concentrations, the drug had no greater impact on suppressing HIV replication. HIV is a virus renowned for its ability to change form and thus evade or develop resistance to therapies designed to stop its action.

Similar testing with entecavir, immune cells and the M184V form of HIV showed that the drug did not stop the virus from infecting the cells. This provided evidence, scientists say, that the drug specifically fostered development of this mutation in HIV, later confirmed by clinical testing.

When researchers tested the blood of one of the co-infected patients for the M184V mutation, they found none in samples taken at the start of entecavir thereapy. But they did find it in 61 percent of viral samples tested after four months of therapy, and 96 percent at six months.


Source:Johns Hopkins Medical Institutions

Related biology news :

1. Widely used iron nanoparticles exhibit toxic effects on neuronal cells
2. Owl genomics presents a HEPATOCHIP for diagnosis of non-alcoholic steatohepatitis
3. Scalpel-free surgery could reduce risk of HIV and hepatitis exposure for health care workers
4. Researchers create infectious hepatitis C virus in a test tube
5. New tools used to control foodborne hepatitis A outbreaks related to green onions
6. Studies clarify risk factors for mother-to-child transmission of hepatitis C virus
7. Past illegal blood donation in China linked to hepatitis C virus infection
8. Texas scientists discover how a hepatitis C protein promotes liver cancer
9. U of S researchers develop new vaccine candidate against hepatitis C
10. Cyclosporine inhibits hepatitis C virus in vitro
11. Novel therapy combinations gain ground in treating hepatitis
Post Your Comments:

(Date:8/15/2017)... HAMPTON, Va. , Aug. 15 2017   ivWatch LLC ... effectiveness of intravenous (IV) therapy, today announced receipt of its ISO ... (QMS) developed by the International Organization for Standardization (ISO┬«). ... ivWatch Model 400 Continuous Monitoring device for ... "This ...
(Date:5/23/2017)... first robotic gym for the rehabilitation and functional motor sense evaluation of ... Italy . The first 30 robots will be available from June ... . The technology was developed and patented at the IIT laboratories and ... thanks to a 10 million euro investment from entrepreneur Sergio Dompè. ... ...
(Date:4/19/2017)... 19, 2017 The global military ... is marked by the presence of several large global ... by five major players - 3M Cogent, NEC Corporation, ... for nearly 61% of the global military biometric market ... the global military biometrics market boast global presence, which ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... New York, NY (PRWEB) , ... October 12, ... ... York Academy of Sciences today announced the three Winners and six Finalists of ... Awards are given annually by the Blavatnik Family Foundation and administered by the ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... United States multicenter, prospective clinical study that demonstrates the accuracy of the ... of identifying clinically significant acute bacterial and viral respiratory tract infections by ...
(Date:10/12/2017)... ... October 12, 2017 , ... AMRI, a global contract ... to improve patient outcomes and quality of life, will now be offering its ... attributed to new regulatory requirements for all new drug products, including the finalization ...
(Date:10/11/2017)... ... October 11, 2017 , ... At its ... announced Dr. Suneel I. Sheikh, the co-founder, CEO and chief research scientist of ... been selected for membership in ARCS Alumni Hall of Fame . ASTER ...
Breaking Biology Technology: