Harmless hepatitis G slows HIV disease

An apparently harmless hepatitis virus appears to slow HIV disease progression dramatically, according to two studies published in this week’s edition of the New England Journal of Medicine. It is the first virus co-infection shown to slow HIV disease progression and inhibit HIV replication in CD4 cells.

Hepatitis G virus, also known as GB virus, is found in about 2% of healthy blood donors in the United States and up to 35% of HIV-positive individuals, and has not been associated with any form of liver disease or other pathology. University of Iowa researchers found that around 40% of HIV-infected individuals in their cohort were infected with GB virus.

When they compared the disease progression rates of people with and without GB virus infection in 362 HIV-positive individuals who received treatment between 1988 and 1999, they found that people without GB virus infection were four times more likely to die.

In the second study, German researchers found that, on average, those with the highest levels of GB virus in their blood had the lowest levels of HIV. Individuals with detectable GB virus had an average viral load -0.7 log below individuals never exposed to GB virus. The German group analysed 197 individuals, 33 of whom had GBV infection, who received care in the period between 1993 and March 2000. The authors do not explicitly report on the relationship between GB viremia and survival after individuals started antiretroviral therapy, but do note that the relationship between GB viremia and survival continued to persist after antiretroviral therapy became available in 1996.

The German group also found that evidence of past exposure to GBVconferred protection; people with antibodies to the virus but no detectable viremia had lower rates of disease progression and lower HIV levels in the blood, although the effect was less than that seen in people with detectable GB viremia. The majority of individuals in the Hanover cohort exposed to GBV appeared to have cleared the infection: 56.0% had antibodies compared with 16.8% with detectable viremia, and the clearance rate is higher among individuals with healthy immune systems.

GB virus has been shown to reduce the rate at which HIV grows in CD4 cells by up to 40% when the cells are co-infected with HIV and GB virus. Understanding the mechanism by which GB virus inhibits HIV replication may provide clues that will help in the development of new treatments.

“It may be reasonable to consider using GBV-C as a novel therapeutic vector to delay disease progression” said Dr Jack Stapleton of the University of Iowa College of Medicine, whose team carried out the research.

“We are now working to understand precisely how GBV-C inhibits HIV from growing,” Dr Stapleton said. “We do not know whether GBV directly interferes with HIV, or if the GBV stimulates cellular proteins, such as interferon or immune cytokines that protect the cells against HIV growth.”

The inhibition of HIV appears to occur after attachment and entry, according to the researchers, and co-infection with GBV did not affect the levels of expression of the CD4, CXCR4 or CCR5 receptors.

GBV is a flavivirus, the family of viruses to which hepatitis C and yellow fever belong. GBV does not affect the severity of hepatitis C virus infection, but the research groups did not report on whether differences were seen in the rate of disease progression between HCV/HIV co-infected individuals and those without HCV/HIV co-infection.

HCV/HIV co-infection has been shown to result in a faster rate of HIV disease progression in some, but not all, studies.