GBV-C is highly transmittable through blood-to-blood contact. Therefore, nearly all IV drug users with either HIV or HCV have probably also been infected with GBV-C. It is also transmitted through sexual contact and some studies have found evidence of current or previous infection with GBV-C in up to 55% of people with HIV.
GBV-C infection can be shown in a couple of ways, through an antibody test (anti-E2) or a viral load test (GBV-C RNA). However, only the GBV-C RNA test can confirm that a person is actively infected with GBV-C. This is because it is possible to become infected with GBV-C, develop antibodies, and then clear the infection while still retaining those antibodies for some time after. Therefore, the anti-E2 only provides evidence that an active infection has occurred at some point in time. It may be current or the body may have cleared it long ago.
To add further complexity, it is believed possible to become infected with GBV-C without ever developing antibodies, and still clear the infection. So some people who test negative for GBV-C RNA and the anti-E2 test may have actually been infected at some point. Gaining this knowledge has been key to developing a better understanding for how GBV-C may be protective against HIV disease progression.
The most recent studies have found that only people who have an active GBV-C infection (i.e., a positive GBV-C RNA test) will also have delayed HIV disease progression, and that this protection is lost when and if the body clears GBV-C. It was reported in some studies at the 2002 CROI that people living with HIV who cleared GBV-C infection may actually be worse off than people who never had GBV-C infection. More recent analysis of this same data indicates this may not be true.
Some researchers, however, remain skeptical that GBV-C infection plays any role at all in delayed HIV disease progression. It has been shown that GBV-C uses CD4+ cells to reproduce, thus competing with HIV. In studies documenting a survival benefit it has been shown that active GBV-C reproduction ceases at the same time as CD4+ counts begin to fall.
A number of researchers interpret this to mean that CD4+ counts are falling because the body has cleared GBV-C. Other scientists argue that the truth may actually be the opposite: when CD4+ cell counts drop, GBV-C no longer has a place to reproduce and is thus eliminated. A study appearing in the June 19 edition of The Lancet may convince at least some skeptics.
The study, out of the Iowa VA Medical Center, tested the degree to which GBV-C was able to reduce HIV replication in cells. In a test tube, HIV-infected cells were infected with different quantities of GBV-C virus. HIV reproduction was significantly decreased in all cell cultures where the strain of HIV in the test-tube was dependent on one of two very common cell receptors (CCR5 or CXCR4). Moreover, the quantity and timing of the dose of GBV-C was strongly linked to the degree by which HIV reproduction decreased.
The researchers were also able to measure the effect of GBV-C and HIV infection on cellular factors that have been identified as protective against HIV. GBV-C-infected cells had fewer receptors like CCR5 on their surface, and they expressed chemical messengers (chemokines) known to block HIV entry into cells. (For more information, read Project Inform's publication, "Co-Receptors-CCR5: Understanding HIV.")
The exact manner by which GBV-C infection accomplishes this is not yet known. These data certainly suggest that examining GBV-C co-infection is a promising avenue for further research. Might it be possible to build drugs based on how GBV-C protects cells? Would it be helpful or possible to infect people with GBV-C as a way to control HIV? Could a strain of GBV-C be used as a vehicle for some kind of gene therapy? The answer to any of these questions may very well lead us toward a cure for AIDS.