A harmless hepatitis virus slows the progression of HIV by stimulating the release of chemokines, according to a study presented in the June 19th edition of The Lancet. The authors suggest that the hepatitis G virus, also known as GBV-C, could be developed as a treatment to slow the progression to AIDS.
Almost 90% of people with HIV show evidence of having been infected with GBV-C, although half of these develop antibodies that clear the virus from their system. Although active GBV-C, like HIV, infects white blood cells, it does not seem to cause any disease, even in people coinfected with HIV.
At least ten previous studies have shown improved survival or other clinical benefits in HIV-positive patients who retain GBV-C for several years. In one pre-HAART study, 75% of HIV-positive men with active GBV-C infection survived at least eleven years, in contrast to only 16% of those who had cleared the virus.
In this study, the investigators, from Iowa, USA, demonstrated that GBV-C acts by increasing the levels of certain chemokines, including one called RANTES (“regulated on activation, normal T cell expressed and secreted”). This protein occupies the CCR5 co-receptor on the surface of CD4 T-cells, thus preventing HIV from binding to and infecting the cells.
The researchers infected white blood cells with HIV and GBV-C, and compared them to cells infected only with HIV. The cells with GBV-C showed increased levels of chemokines, including RANTES, preventing the fusion of HIV with its target cells. However, when they neutralised the chemokines with antibodies, they saw that the protective effect of GBV-C was lost.
Although there are a number of drugs under development that mimic the action of RANTES, the study’s authors believe that the GBV-C virus itself could be used as a treatment, because of its safety. Furthermore, in contrast to the fusion inhibitor T-20 (enfuvirtide, Fuzeon), which needs to be injected twice daily, patients may only need a few exposures to see a benefit.
“The fact that GBV-C is such a common infection, and that it’s been so extensively studied and not shown to cause any diseases, distinguishes it from other live viruses,” said the study’s senior investigator, Dr Jack Stapleton. “This makes it a more realistic option.”
However, “it is possible to lose the virus,” said Stapleton. “The next thing we have to do is … learn how to make it persist, so it can continue to induce these chemokines and these changes in the cell that help HIV.”
The authors note that the effect of GBV-C on HIV viral loads is similar to HAART, although “HIV probably doesn’t become resistant to GBV-C very easily.”
Further information on this website
Harmless hepatitis G virus slows HIV disease - news story
Persistent HIV/hepatitis G co-infection provides significant survival benefit - news story
Xiang J et al. Inhibition of HIV-1 replication by GB virus C infection through increases in RANTES, MIP-1, MIP-1ß, and SDF-1. Lancet 363: 2040-2046, 2004.