March 3, 2004
Men infected with both HIV and GB virus type C (GBV-C), previously known as hepatitis G, for at least five years were three times less likely to die than HIV-positive men who did not have GBV-C. The study, funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, appears in the March 4 issue of The New England Journal of Medicine.
"We found strong evidence that HIV-positive men who have persistent GBV-C infection survive longer than those who do not have GBV-C. The survival advantage is large and depends on how long the GBV-C infection persists," says senior investigator Jack Stapleton, M.D., of the University of Iowa and Iowa City Veterans Affairs Medical Center. Carolyn Williams, Ph.D., epidemiology branch chief in NIAID's Division of AIDS, was the lead investigator on this study.
GBV-C, a virus that infects white blood cells, does not cause any known disease. It is transmitted through blood and blood products, and many people carry the virus, some for up to 40 years. Earlier studies have reported improved survival for HIV-positive persons co-infected with GBV-C, but the idea has been controversial. While some investigators found a survival advantage for HIV-positive men with GBV-C infection, others did not. This new study is the first to take into account the duration of GBV-C infection.
Dr. Williams and NIAID established a collaboration between the Multicenter AIDS Cohort Study (MACS) and Dr. Stapleton's laboratory in hopes of finding conclusive evidence on whether GBV-C infection prolonged the lives of HIV-positive men. The MACS, a long-term ongoing study of men who have sex with men, allows researchers to examine various factors that affect the progression of HIV infection and AIDS. Blood samples preserved by the MACS enabled Dr. Stapleton's group to determine whether there were differences in survival of HIV-positive men based on whether and for how long they had GBV-C infection.
Their results show that men who had GBV-C infection in two blood samples taken at least five years apart lived the longest. Eleven years after contracting HIV, 75 percent of the men who had GBV-C in both these blood samples were alive. Of the men who did not have GBV-C in either blood sample, only 39 percent survived for 11 years. The men who had GBV-C in their first blood sample but not in the second had the greatest risk of dying. Only 16 percent of them were still living after 11 years.
The researchers studied 271 MACS participants who became HIV-positive only after enrolling in MACS. The MACS provided Dr. Stapleton's team with blood samples for each man in the study group. Early blood samples for all 271 participants were drawn within 18 months of when the participant contracted HIV. Later blood samples -- for various reasons, available for only 138 of the 271 participants -- were drawn five to six years later. The researchers used blood samples collected before Jan. 1, 1996, to examine the interaction of the two viruses in this group of individuals before the widespread use of newer AIDS drugs in highly active antiretroviral therapy.
The researchers analyzed survival of the HIV-positive men based on whether they did or did not have GBV-C infection in their early blood sample. Using only the early blood sample data, the researchers found that men who had GBV-C did not survive any longer than those who did not. This finding is consistent with previous studies that did not find a survival advantage in early GBV-C infection for HIV-positive men co-infected with GBV-C.
Investigators then evaluated survival based on whether the men were still infected with GBV-C in their later blood sample. These MACS findings suggest that the survival advantage associated with GBV-C is evident only for HIV-positive men who have long-term infection with GBV-C, and that the previous studies did not find this advantage because they did not consider the duration of the GBV-C infection.
Why men with persistent GBV-C infection survive longer is not known, the researchers say. Dr. Stapleton's studies on cells grown in the laboratory suggest that GBV-C inhibits HIV from growing in human cells. However, the researchers also acknowledge that other factors related to the individual or to HIV might also be responsible for the survival advantage. Previous studies of GBV-C and HIV have shown that people infected with both viruses had slower decline in the number of key immune system cells compared to HIV-positive individuals who didn't have GBV-C infection. The MACS study confirms these findings as well. Dr. Stapleton's team and the MACS study group are continuing this work to help understand why and how GBV-C gives HIV-positive men a survival advantage.
Questions remain as to why some of the men cleared the GBV-C virus from their systems and why this was associated with an earlier death. Additional studies could answer these questions and offer new insights on how to control the progression of AIDS.
Researchers at Johns Hopkins University, Northwestern University, University of Pittsburgh, University of California, Los Angeles and Roche Diagnostics are co-authors on the new paper.