Understanding of GBV-C Virus Effect on HIV and Survival

IOWA CITY, Iowa -- In the largest study of its type to date, a University of Iowa Health Care investigation confirms that people with HIV infection who also are infected with a virus known as GB Virus type C (GBV-C) live longer than those people who are HIV-positive but are not co-infected with GBV-C.

The UI study also found in a laboratory-based model that GBV-C reduces the growth rate of HIV in cultured human T-cells. The results appear in the Sept. 6 issue of the New England Journal of Medicine (NEJM).

The clinical portion of the UI study focused on blood samples and mortality data of 362 patients with HIV who were seen at the HIV/AIDS Clinic at the UI over a 12-year period. Among these HIV-infected individuals, 144 also had GBV-C.

"Four previous clinical studies examined the relationship between GBV-C and HIV," said investigator Jack Stapleton, M.D., UI professor of internal medicine and a staff physician and researcher at the Veterans Affairs (VA) Medical Center in Iowa City. "However, our UI studies involved 50 percent more GBV-C and HIV co-infected patients than the previous studies combined. In addition, our laboratory studies are the first to demonstrate an inhibitory effect of GB virus C on HIV."

He added that, together, the UI clinical and laboratory findings suggest that the GBV-C infection may explain, at least in part, why some patients remain healthy for long periods of time with HIV infection, while others rapidly become very ill or die.

"Eventually, these findings may help to develop a new approach to HIV therapy, either by using the virus itself, or by using GBV-C proteins to activate other proteins or immune responses that could inhibit HIV," Stapleton said.

Stapleton explained that, early on, GBV-C was known as hepatitis G virus because it is a very close relative of hepatitis C virus and was initially found in people who had chronic hepatitis but who did not have hepatitis A, B, C, D, E or F. Consequently, one group of investigators called it hepatitis G. Subsequent studies showed that it does not cause hepatitis or any other disease, thus the name hepatitis G is misleading.

In the United States, approximately 1.8 percent of healthy blood donors are infected with GBV-C. However, because the virus does not cause any disease, the U.S. Food and Drug Administration does not screen blood units for the virus.

"Although GBV-C is very common in humans, it does not appear to cause any disease. Once it was learned that it did not actually cause hepatitis, many researchers stopped studying it," Stapleton said. "We continued to study it because we thought it might serve as a model to understand hepatitis C virus, and because we were interested in how it grows in people in spite of several unusual properties."

In the UI study, nearly 40 percent of the HIV patients (144 individuals) had GBV-C, an infection rate similar to that found in previous studies of HIV patients. Among those 144 people co-infected with GBV-C and HIV, slightly more than 28 percent had died compared to nearly 56 percent of the people who had HIV without GBV-C co-infection.

"We expanded the previous research by looking at a very large group of patients followed at our clinic between 1988 and 2000, and we found that HIV-infected people without GBV-C infection were 3.68 times more likely to die than those with GBV-C," Stapleton said. "This makes us think that GBV-C is one factor in why some people live longer and more healthily with their HIV infection than other HIV-infected people do."

The laboratory portion of the UI study used an infectious molecular clone of GBV-C developed by Jinhua Xiang, M.D., and HIV culture systems developed by Sabina Wunschmann, Ph.D., and Donna Klinzman. Xiang and Wunschmann are UI research scientists in Stapleton's laboratory, and Klinzman is a research associate at the Iowa City VA Medical Center.These cell cultures showed that GBV-C grows in CD-4 positive T-cells, the same type of cell that HIV grows in.

"We found that cells infected with both GBV-C and HIV produced 30 to 40 percent less HIV than cells infected only with HIV," Stapleton said."We're now working on understanding how GBV-C inhibits HIV from growing," he added. "We don't know whether GBV-C directly interferes with HIV, or if the GBV-C stimulates cellular proteins, such as interferon or immune cytokines, that protect the cells against HIV growth."

Most of the 362 patients in the clinical portion of the study initially received treatment at the UI before the availability of Highly Active Anti-Retroviral Therapy (HAART), better known as the HIV drug-cocktail.

"Of the 47 HIV-infected patients who entered our clinic after HAART was available in 1995, we had only one death," Stapleton said. "Therefore, based on our study, we can't really say that GBV-C was beneficial among those who have received HAART, since almost all the patients did well."

A study on GBV-C and HIV by a group of German investigators also appears in the Sept. 6 issue of the NEJM. In that study, GBV-C was also shown to be beneficial in patients studied after the availability of HAART treatment.

Stapleton and his colleagues continue to study how GBV-C may inhibit HIV. The UI investigators are well suited for this work because they have been involved in the study of hepatitis viruses for more than 15 years and GBV-C for five years, and they have provided primary medical care and offered clinical research projects for HIV-positive people.

The HIV/AIDS Clinic at the UI was started in 1988 by Stapleton, who came to Iowa to organize the clinic and set up the hepatitis research laboratory. He also is director of the Helen C. Levitt Center for Viral Pathogenesis and Disease at the UI.

The UI study was supported in part by a Merit Review grant and two Career Development awards from the U.S. Veterans Administration and by a grant from the National Institute on Alcohol Abuse and Alcoholism, one of the National Institutes of Health.

In addition to Stapleton, Xiang, Wunschmann and Klinzman, UI investigators involved in the study included Daniel Diekema, M.D., UI assistant professor (clinical) of internal medicine and a staff physician at the VA Medical Center in Iowa City; Kevin Patrick, program assistant in internal medicine; and Sarah George, M.D., fellow associate in internal medicine.

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CONTACT: Becky SoglinUnversity of IowaHealth Science Relations(319) 335-6660fax (319) 384-4638[email protected]