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Hepatitis G May Boost HIV Survival

By Merritt McKinney
NEW YORK (Reuters Health) - A form of hepatitis virus not believed to cause illness may improve survival in people who have HIV, the virus that causes AIDS.

In two new studies, HIV-positive people who were also infected with the hepatitis G virus tended to live longer than other people infected with HIV. Researchers suspect that hepatitis G, which is also known as GB virus C (GBV-C), improves survival by keeping HIV from replicating as often.

Hepatitis G, which was identified in the mid-1990s, is closely related to the hepatitis C virus. But unlike hepatitis C, which can cause serious liver disease, hepatitis G is not thought to cause illness. Nearly 2% of healthy blood donors test positive for the virus, and more than one third of HIV-positive individuals may carry the virus.

The findings may open the door to new types of HIV treatment with hepatitis G, researchers suggest.

"We are working to try to understand the mechanism of the HIV inhibition" apparently caused by hepatitis G, Dr. Jack T. Stapleton, of the University of Iowa and the Iowa City Veterans Affairs Medical Center, told Reuters Health. Stapleton is the lead author of one of two reports on hepatitis G and HIV survival that appear in the September 6th issue of The New England Journal of Medicine.

"If we can determine how (hepatitis G) infection diminishes HIV growth, we will have both potential targets for new drug approaches and potentially a new therapy approach," he said.

The Iowa researcher cautioned, however, that infection with hepatitis G is very common in HIV-infected people, which may limit the therapeutic use of the virus.

"Many people have previously been infected with the virus and their immune systems cleared the infection," he said. "It is unlikely that these people can be re-infected with (hepatitis G)."

Several earlier studies had demonstrated a link between hepatitis G and prolonged survival with HIV, so Stapleton and his colleagues conducted a study to confirm the connection.

Among 362 patients with HIV, infection with hepatitis G was common, occurring in about 40% of patients. Stapleton and his colleagues found that over the course of about 4 years, the risk of death was almost four times greater in patients who did not have hepatitis G than in those who carried the additional virus.

Stapleton's team performed another set of experiments to try to find out how hepatitis G behaves in the presence of HIV. In these laboratory tests, HIV replicated more slowly when exposed to hepatitis G, the report indicates.

"GBV-C infection in HIV-infected individuals was associated with slower HIV disease progression," Stapleton said. "Based on our laboratory data, this may be due to an inhibitory effect."

However, he noted that the findings apply only to HIV-positive individuals in the era before the introduction of effective HIV therapy. He explained that there were too few deaths in study patients after 1996, when "drug cocktails" were introduced, to detect a difference in the risk of death.

Stapleton and his colleagues are involved in ongoing research to find out whether the results of the study are applicable to patients in less developed regions of the world as well as in HIV-positive people who are being treated with combination therapy.

A team led by Dr. Hans L. Tillmann, at the Medizinische Hochschule Hannover in Germany, also reports that HIV-positive people who carry hepatitis G seem to live longer.

In a study of nearly 200 HIV-positive people who were followed from 1993 or 1994, patients who had hepatitis G tended to live longer and to take longer to progress to full-blown AIDS. And after they developed AIDS, patients with hepatitis G tended to live longer. The German researchers also found that patients with high levels of hepatitis G virus had lower levels of HIV in their blood.

Tillmann and his colleagues also uncovered evidence that hepatitis G may provide a survival advantage to patients after the introduction of combination therapy. In addition, the link between hepatitis G and longer survival remained statistically significant even after researchers accounted for several factors, including age, sex and levels of certain immune system cells.

"Understanding the mechanism of interaction of HIV and GBV-C might enable new treatment options," Tillmann told Reuters Health. But "there is still a lot of work to be done" in learning about the relationship between hepatitis G and HIV survival, he said. In the next year Tillmann said he hopes to prove that eliminating hepatitis G from the body is bad for people with HIV.

The apparent link between HIV survival and hepatitis G may eventually have an impact on the treatment of hepatitis C in HIV-positive people, he said.

Although Tillmann cautioned that it is too soon to make a conclusion, he would recommend testing for hepatitis G before using interferon to treat hepatitis C in HIV-positive patients. This treatment, he said, might lead to clearance of the seemingly beneficial hepatitis G.

Despite the apparent connection between hepatitis G and prolonged survival with HIV, it would be premature to consider using hepatitis G as a therapy for HIV, according to an editorial accompanying the study.

"There are many questions that remain to be answered and many elements of the story that remain to be discovered," according to Drs. Valentina Stosor and Steven Wolinsky at Northwestern University Medical School in Chicago, Illinois.

Because the long-term effects of infection with hepatitis G are unknown, as well as the fact that the virus often is accompanied by other disease-causing infections, intentionally infecting people with hepatitis G is "inadvisable and inherently dangerous," the editorialists conclude.

SOURCE: The New England Journal of Medicine 2001;345:707-724, 761-762.