Cross-resistance alarms raised earlier this year by Johns Hopkins researchers about a widely used antiviral therapy for hepatitis B liver infections have prompted swift treatment revisions by the drugs maker and governmental agencies.
Findings by a team of
As a result of the studys initial presentation in February at the 2007 Conference on Retroviruses and Opportunistic Infections (CROI), Bristol-Myers Squibb, the drugs manufacturer, changed its product labeling to warn of the potential for HIV drug resistance, notified prescribing physicians and informed the U.S. Food and Drug Administration. The U.S. Department of Health and Human Services (HHS) also revised its treatment guidelines. HHS now recommends against using entecavir, better known by its brand name Baraclude, as the first option in treating hepatitis B in co-infected patients who are not already using drugs to suppress HIV.
Many co-infected patients and their physicians are justifiably concerned about whether or not to use the drug, says senior study author Chloe Thio, MD. She notes that more than 4 million people worldwide are believed to be infected with both viruses.
Patients contending with both diseases should consult with their physician to see if entecavir is the right drug to treat their hepatitis B in the first place, because the drug still works against the liver disease, or if they should refrain from taking it because of the potential for HIV drug resistance, says Thio, an associate professor of medicine at The Johns Hopkins University School of Medicine.
Hepatitis B infection attacks the liver and can lead to cirrhosis, liver cancer or even death from liver failure.
Co-infected patients already on entecavir should consult with their physician before stopping therapy and about having blood testing done to monitor for any signs of drug resistance that could potentially compromise subsequent anti-HIV therapy, she says.
In the published study, researchers documented three cases of co-infected patients from
Since the results were presented at CROI, researchers have substantiated their findings with several more cases from across the
Researchers say their next step is to better understand the mechanism by which entecavir interferes with the enzyme, called reverse transcriptase, which is involved in viral replication. Their goal is to better understand how drug resistance develops, including the M184V mutation. They also plan to look for evidence of any other HIV mutations.
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. More than 1.2 million Americans are infected with hepatitis B.
Other Hopkins investigators involved in this research, which was supported by funding from the National Institutes of Health, were Moira McMahon, B.Sc.; Benjamin Jilek, BSc; Timothy Brennan, MS; Lin Shen, BSc; Yan Zhou, PhD; Megan Wind-Rotolo, Ph.; Sifie Xing; Shridhar Bhat, PhD; Robert Hegarty, CRNP; Curtis Chong, BSc; Jun Liu, PhD; and Robert Siliciano, MD, PhD. Siliciano is also a Howard Hughes Medical Institute investigator. Additional assistance from the Naval Medical Center in San Diego was provided by Braden Hale, MD.
Source: Johns Hopkins