Coinfection with HIV and GB Virus C (GBV-C) Infection Is Significantly Associated with Prolonged Survival 5 to 6 Years after HIV Seroconversion

GB virus C (GBV-C), an RNA virus in the Flaviviridae family, is a close relative of the hepatitis C virus (HCV). Fortunately for mankind, unlike its cousin HCV, GBV-C has no clear association with a known disease state.

GBV-C has been shown to replicate in human peripheral-blood mononuclear cells in vitro, and it commonly coinfects patients with HIV. GBV-C is transmitted through predominantly parenteral routes and has a high seroprevalence among intravenous-drug users. Nonetheless, the sexual transmission of GBV-C has also been demonstrated recently.

GBV-C, which is not known to be pathogenic in humans, replicates in lymphocytes, inhibits the replication of HIV in vitro, and has been associated with a decreased risk of death among HIV-positive persons in some, but not all, studies.

Previous studies did not control for differences in the duration of HIV or GBV-C infection.

Researchers evaluated 271 men who were participants in the Multicenter Acquired Immunodeficiency Syndrome Cohort Study for GBV-C viremia (by means of a reverse-transcriptase–polymerase-chain-reaction assay) or E2 antibody (by means of an enzyme-linked immunosorbent assay) 12 to 18 months after seroconversion to positivity for HIV (the early visit); a subgroup of 138 patients was also evaluated 5 to 6 years after HIV seroconversion (the late visit).

Results

GBV-C infection was detected in 85 percent of men with HIV seroconversion on the basis of the presence of E2 antibody (46 percent) or GBV-C RNA (39 percent). Only one man acquired GBV-C viremia between the early and the late visit, but 9 percent of men had clearance of GBV-C RNA between these visits.

GBV-C status 12 to 18 months after HIV seroconversion was not significantly associated with survival; however, men without GBV-C RNA 5 to 6 years after HIV seroconversion were 2.78 times as likely to die as men with persistent GBV-C viremia (95 percent confidence interval, 1.34 to 5.76; P=0.006).

The poorest prognosis was associated with the loss of GBV-C RNA (relative hazard for death as compared with men with persistent GBV-C RNA, 5.87; P=0.003).

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.

Conclusions

GBV-C viremia was significantly associated with prolonged survival among HIV-positive men 5 to 6 years after HIV seroconversion, but not at 12 to 18 months, and the loss of GBV-C RNA by 5 to 6 years after HIV seroconversion was associated with the poorest prognosis.

According to the authors, “Understanding the mechanisms of interaction between GBV-C and HIV may provide insight into the progression of HIV disease.”

03/10/04

References

C F Williams and others. Persistent GB Virus C Infection and Survival in HIV-Infected Men. The New England Journal of Medicine 350(10): 981-990. March 4, 2004.

R J Pomerantz and G Nunnari. HIV and GB Virus C-- Can Two Viruses Be Better Than One? The New England Journal of Medicine 350(10): 963-965. March 4, 2004.