GB Virus C Infection in HIV/HCV Coinfected Patients Receiving Hepatitis C Treatment

By Liz Highleyman

GB virus C (GBV-C), formerly known as hepatitis G virus, is related to hepatitis C virus (HCV), but does not appear to cause liver disease.

Though studies to date have yielded conflicting results, persistent infection with GBV-C appears to be associated with slower HIV disease progression. This finding has led some to speculate that interferon-based hepatitis C therapy, which is also active against GBV-C, might have a deleterious effect in HIV/HCV coinfected individuals.

Researchers with the AIDS Clinical Trial Group A5071 Study Team sought to determine the prevalence of GBV-C in HIV/HCV coinfected patients, the relevance of different GBV-C genotypes to HIV disease progression, and the impact of hepatitis C treatment on GBV-C clearance. They retrospectively studied 130 HIV/HCV coinfected patients initiating treatment with conventional or pegylated interferon plus ribavirin.

Results

Current or past GBV-C infection (indicated by GBV-C viremia or E2 antibody positivity) was identified in 111 patients (85%).

Ongoing GBV-C replication was detected in 40 patients.

Coinfection with genotype 2 GBV-C was associated with significantly higher CD4 cell counts.

After 24 weeks of HCV therapy, GBV-C RNA clearance was observed in 50% of patients.

GBV-C clearance at 24 weeks was strongly correlated with HCV virological response.

Factors predicting clearance during treatment were similar for the two viruses.

GBV-C clearance was associated with use of pegylated (rather than conventional) interferon plus ribavirin, and with a higher baseline CD4 cell count.

Sustained GBV-C clearance was observed in 31% of patients who had detectable GBV-C at baseline.

GBV-C clearance was not associated with changes in HIV load or CD4 cell count.

Conclusion

In conclusion, the authors wrote, "GBV-C RNA clearance with HCV therapy was associated with neither short-term loss of HIV control nor impaired immune status." They added that the association of GBV-C genotype 2 with higher CD4 cell counts merits further study.

In their discussion, the researchers noted that the prevalence of GBV-C viremia was higher among younger patients, whereas E2 antibodies were detected more frequently among older patients, suggesting that E2 antibodies may protect against GBV-C reinfection. However, 11 patients were simultaneously positive for both GBV-C RNA and E2 antibodies. Similar results have been seen in other HIV/HCV coinfected patients, suggesting that this may be "attributable to altered immune responses in the setting of HCV/HIV coinfection or reinfection with GBV-C in the presence of E2 antibodies."

The authors further noted that several studies have described a beneficial effect of GBV-C viremia on the HIV disease progression. Various mechanisms by which GBV-C infection might exert such an effect have been proposed, including post-entry inhibition of HIV replication, alteration of T-helper cytokine profiles, and changes in chemokine co-receptor expression. However, they emphasized that this beneficial effect of GBV-C on the HIV disease progression has not been observed in all studies, and suggested that other virological and immunological factors may partially explain these conflicting results.

Importantly, the authors stated, GBV-C RNA clearance did not appear to be associated with short-term loss of HIV RNA control in this study, suggesting that the effects of GBV-C on HIV may be outweighed by effective HAART (which was used by a majority of study participants).

Editorial

In an accompanying editorial, Mark Berzsenyi and Stuart Roberts presented an overview of the current state of knowledge concerning GBV-C and HIV infection, noting that, "there is still considerable controversy regarding this interaction." By contrast, it is more evident that GBV-C has little, if any, effect on HCV infection, liver disease progression, or interferon-based therapy.

The ACTG A5071 study found that GBV-C clearance did not have a deleterious impact on HIV disease progression in the short term, but further studies are needed to assess "whether patients who clear GBV-C are more vulnerable to the progression of HIV disease in the longer term." The study also found no beneficial effect of GBV-C infection on baseline CD4 cell count and HIV load, "adding further fuel to the debate about whether GBV-C modulates the course of HIV infection."

Speculating as to the reason for conflicting results from this and past studies, Berzsenyi and Roberts suggested that several confounding factors likely contribute to the disparity, including initiation of HAART, differences between study populations, and possibly the presence of HCV. "In particular," they wrote, "differences in GBV-C genotype distribution among different populations could affect the progression of HIV disease."

Further, they noted that individuals in this study who achieved temporary or sustained GBV-C clearance did not develop E2 antibodies, suggesting that -- contrary to popular belief -- these antibodies may not be a particularly useful marker for past GBV-C infection in patients with HCV, HIV, or both.

"Without question, the interactions among GBV-C, HCV, and HIV are complex," the authors concluded. "All the work performed to date in triply infected individuals has focused primarily on HIV-related outcomes; however, important questions still remain. Of great importance among these questions is the role that GBV-C infection plays in the progression of liver disease in the HCV/HIV coinfected patient…Only once these questions are addressed will we be able to begin to fully appreciate the associations between GBV-C and HCV/HIV coinfection and to understand their potential clinical impact."

7/25/06

References

C Schwarze-Zander, J T Blackard, H Zheng, and others (for the AIDS Clinical Trial Group A5071 Study Team). GB Virus C (GBV-C) Infection in Hepatitis C Virus (HCV)/HIV-Coinfected Patients Receiving HCV Treatment: Importance of the GBV-C Genotype. Journal of Infectious Diseases 194(4): 410-419. August 15, 2006.

M D Berzsenyi and S K Roberts. What Is the Role of GB Virus C Infection in Hepatitis C Virus/HIV Coinfection? Journal of Infectious Diseases 194(4): 407-409. August 15, 2006.

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