University of Iowa News Release
March 4, 2004
Study Adds Evidence That GBV-C Virus Extends Survival With HIV
A study performed at the University of Iowa and the Iowa City Veterans Affairs Medical Center (VAMC) adds compelling evidence that men persistently co-infected over the long-term with HIV and the harmless GB Virus type C (GBV-C) live longer than men infected only with HIV. At the end of five- to six-year intervals, the co-infected men were nearly three times more likely to be alive.
The findings have implications for the development of new treatment strategies to slow HIV disease. The study, which appears in the March 4 issue of the New England Journal of Medicine, expands on previous co-infection studies by controlling for differences in how long men were infected with HIV and GBV-C.
The investigation utilized HIV-infected patients participating in a long-term study, the Multicenter AIDS Cohort Study (MACS), which is funded by the National Institutes of Health (NIH). UI researchers evaluated blood samples stored from these patients for evidence of GBV-C infection and worked with Carolyn Williams, Ph.D., researcher at the National Institutes of Allergy and Infectious Diseases and lead author of the paper, to analyze the effects of GBV-C on HIV disease and mortality.
Jack Stapleton, M.D., professor of internal medicine at the UI Roy J. and Lucille A. Carver College of Medicine and director of the UI AIDS Clinic, was the corresponding author for the study. The study confirms and expands findings published in 2001 by Stapleton's group. Stapleton also is a staff physician and researcher at Iowa City VAMC, and director of the UI Helen C. Levitt Center for Viral Pathogenesis.
"Men who were persistently co-infected with HIV and GBV-C did significantly better than HIV-positive men who never had any evidence of GBV-C. We were motivated to prove that our earlier study was accurate because it is an unusual finding, and many people are reluctant to accept our earlier findings," Stapleton said.
GBV-C causes no disease in humans, and Stapleton said that other studies in human cell models in the UI laboratory indicate that the virus inhibits HIV growth.
"Hopefully, these results will motivate more people to study this virus. A potential result is that it may lead to new treatment strategies that delay the progression of HIV disease. These strategies might require limited use and thus would potentially be inexpensive and used throughout the world," Stapleton said.
The men studied were a subset of individuals who enrolled between 1984 and 1990 in the MACS, which is ongoing in Baltimore, Pittsburgh, Chicago and Los Angeles. The study involved blood samples from these 271 men who initially were HIV-negative when they entered the study, and became HIV-positive during the follow-up when blood samples were obtained every six months. Thus, the time that they became HIV-infected is known within a six- to 12-month interval. The previous study at the UI and other published studies did not have information about when men truly had acquired HIV. The samples analyzed by the UI in this study did not include blood taken after 1996 because of the advent of highly effective AIDS drug cocktail therapies, which make studies of survival and HIV disease progression difficult to interpret.
Stapleton's VA research laboratory analyzed blood samples from two crucial time points for 138 participants: within 18 months of developing HIV and five to six years after developing the condition. For various reasons, not all of the original 271 participants provided blood samples at the later date.
"At that second time-point, we found that those men who were persistently infected with GBV-C survived significantly longer than those who were persistently negative for GBV-C," Stapleton said.
Additional tracking 10 to 11 years beyond the participants' initial HIV infection revealed a survival rate of 75 percent among HIV-positive men also infected over the long term with GBV-C. In contrast, 39 percent of the HIV-positive men who never had GBV-C infection detected had a 10- to 11-year survival rate.
Stapleton said a surprising finding was that men with HIV who initially had the GBV-C infection but cleared it between their early and five or six-year visit had an 11-year survival rate that was even lower than that of HIV-positive men who never had any GBV-C. Only 16 percent of those who cleared their GBV-C infection were alive, suggesting that short-term GBV-C infection has none of the protection associated with long-term GBV-C infection. Additional research is needed to understand this difference.
Jinhua Xiang, M.D., UI research scientist in internal medicine and a researcher at the Iowa City VAMC who works with Stapleton, found in a previous study that GBV-C grows in the same type of important immune cells in which HIV grows. One of the functions of HIV is to destroy these CD4+ T-cells, also known as helper T-cells, and this destruction of helper T-cells causes the immune deficiency.
"People with GBV-C have a slower rate of destruction of helper T-cells," Stapleton said. "However, once HIV starts destroying cells needed for GBV-C, you lose its apparent effect."
Stapleton's laboratory and the MACS will continue to investigate how GBV-C relates to long-term survival with HIV.
"We think it actually is a causative connection, but this point is debated and needs more study. It may be important to study whether infecting people intentionally with GBV-C will be advantageous or not," Stapleton said.
Further studies already are under way to see if the beneficial effects of GBV-C will be seen in HIV-positive women.
Approximately one of every 50 to 70 units of donated blood in the United States contains the harmless GBV-C virus. Because the virus causes no disease, the Food and Drug Administration does not require screening for it.
In addition to NIH funding, the study included support from the National Cancer Institute and a Veterans Affairs Merit Review award to Stapleton.
The collaborative study involved MACS centers at Johns Hopkins University in Baltimore, Northwestern University in Chicago, the University of Pittsburgh, and the University of California at Los Angeles. In addition, researchers at Roche Diagnostics participated in the study. For more information on MACS, visit www.niaid.nih.gov/reposit/macs.htm.
For information on Stapleton's previous findings published in 2001, see this news release at http://news-releases.uiowa.edu/2001/september/0906gbv-c-virus.html.
University of Iowa Health Care describes the partnership between the UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide. Visit UI Health Care online at http://www.uihealthcare.com.
STORY SOURCE: University of Iowa Health Science Relations, 5137 Westlawn, Iowa City, Iowa 5224-1178
MEDIA CONTACT: Becky Soglin, 319 335-6660 firstname.lastname@example.org
PHOTO: A photo of Jack Stapleton is available for downloading at http://www.int-med.uiowa.edu/Divisions/ID/Directory/JackStapleton.html.