CONTACT: BECKY SOGLIN
Iowa City IA 52242
(319) 335-6660; fax (319) 384-4638
Release: Sept. 6, 2001
UI studies GBV-C virus effect on survival of HIV-positive people
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
"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
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
"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 Wünschmann, Ph.D., and Donna Klinzman. Xiang and Wünschmann
are UI research scientists in Stapletons 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, Wünschmann 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.
University of Iowa Health Care describes the partnership between
the UI College of Medicine and the UI Hospitals and Clinics and the patient
care, medical education and research programs and services they provide. Visit
UI Health Care online at www.uihealthcare.com.