What a difference a decade makes, particularly for such deadly viruses as HIV and HBV. Today, the Hepatitis B Foundation has made the problems associated with HIV-HBV co-infections one of its national priorities. Improving drug combinations provide new hope, but difficult challenges remain in treating and managing these two viruses.
Worldwide, HBV chronically infects 400 million people; approximately 40 million are infected with HIV. In the 1990s, individuals who were infected with HIV had little chance to survive the deadly progression of the virus. But the advent of a powerful cocktail of antiviral agents has turned HIV infection into a chronic condition with which people can live for decades.
And for those with HBV, well, there was interferon – which sometimes worked and sometimes didn’t, and carried significant side effects for many – and little else. But now, newer, more powerful antiviral drugs such as lamivudine, adefovir, entecavir, and tenofovir – with still more in the development pipeline, have enabled those with chronic HBV to increasingly stave off the effects of hepatitis for years as well.
While a so-called “cure” isn’t around the corner, the outlook for HBV and HIV infected individuals is better than ever before. But the situation is a little more complicated for those infected with both viruses – estimated at between 5 to 8 million individuals in the world and rising. In the U.S., about 8 percent of all HIV-infected persons also harbor HBV, though the figure is higher in Asia and sub-Saharan Africa.
While the numbers are growing, the combination of the two infections has turned out be an even more daunting challenge to healthcare professionals than each virus alone.
One reason is that HIV often makes HBV infection worse. Liver disease can progress more rapidly in those patients who are co-infected, leading to cirrhosis and liver cancer developing at earlier ages.
“Now that we can treat HIV, co-infection is becoming more significant and liver disease is becoming a more common cause of death in HIV-infected persons,” said David Thomas, M.D., professor and chief of infectious diseases at Johns Hopkins University School of Medicine in Baltimore. “It’s an important problem, and we’d like to understand more about why this happens.”
Robert Gish, M.D., chief of the Division of Hepatology and medical director of the liver transplant program at California Pacific Medical Center in San Francisco, explained that HIV-infected individuals are immune-suppressed and less likely to clear the HBV spontaneously. “Because they are immune-suppressed, the HBV DNA level is very high. The immune system is not controlling the virus well and that may be driving a lot of the liver damage,” he said. “People with both have double to triple the rate of cirrhosis, and an increased risk of death from liver disease.” Additionally, HIV medications can increase the risk of liver injury in those with chronic liver disease.
There are other complications with HIV co-infected persons. Gish noted that a weakened immune system can allow an HBV infection – though cleared from the body, but actually not – to resurface more easily.
According to Gish, HBV-infected individuals run a greater risk of also being infected with HCV and possibly other viruses. “Often, other viruses piggyback with HBV,” he said. “Combinations of two, three or more of them with HIV make the risk of cirrhosis extremely high.”
Preventing HBV infection in HIV-infected individuals becomes harder as well, Gish said. One reason is that they don’t respond as well to the HBV vaccine. Some HIV patients don’t receive it in time to prevent infection.
Treatment Issues
Not surprisingly, there are treatment issues as well for HIV-HBV co-infected patients. Treating two viruses at once is complex, and the specter of drug resistance is always nearby.
Several antivirals available to treat HBV also work against HIV, including lamivudine, emtricitabine and tenofovir. A new medication, Truvada, combines tenofovir and emtricitabine in one pill, “representing an important breakthrough for the management of those with dual infections,” said Thomas. He noted that tenofovir isn’t yet approved for HBV, but is being used already. “We clearly feel that the combination is the treatment of choice when treating both HIV and HBV.”
“All of the drugs are effective and safe,” said Raymond Schinazi, Ph.D., professor of pediatrics and chemistry at Emory University School of Medicine in Atlanta. “The only issue is the emergence of resistance. You have to be careful giving these drugs to co-infected individuals.” Entecavir, which was originally thought to only work against HBV, subsequently demonstrated activity against HIV also, and has since been found to present a risk for the development of resistance in HIV patients, he explained.
Some patients may already have their HIV under control, and may only need treatment for HBV. “One of the questions is, when treating HBV alone, what is the best way to treat it?” said Thomas.
“For those patients, we’re stuck,” Thomas said. “We can use telbivudine and adefovir, but they have high rates of resistance. We can use interferon, but it has side effects and needs to be injected and not everyone likes to take that. That represents one of the challenges in the field.”
“There is a drug pipeline for HBV and HIV, and every drug will be scrutinized for dual activity,” Thomas added.
Gish said that finding ways to clear HBV from the body without suppressing it is a priority. “Clinically, it’s to find the right drug combination and the right time and the right patient to avoid treating the wrong virus too early with the wrong combination, which can lead to resistance.”
While the ultimate goal for treating both viruses is eradication, said Schinazi, “the challenges are going to be to learn how to block resistance and to know when to stop treatment. Those are going to be the big challenges down the road for both viruses.”
Steve Benowitz, science writer, Philadelphia
