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Focus on Hepatitis: Does GB Virus C Protect Against HIV Disease Progression?

February 2005

Editor's Note: This article was first e-published February 3, 2005, at www.aidsmap.com.

Coinfection with hepatitis G (or GB virus C) may not be a protective factor in the progression of HIV disease, according to a longitudinal study presented in next month's edition of the Journal of Infectious Diseases.1 The study found that loss of the virus was associated with faster progression and decreases in CD4 count, leading the authors to suggest that HIV disease progression may be a cause, not a consequence, of the loss of GB virus C.

GB virus C is a harmless virus that is closely related to hepatitis C virus (HCV). A number of studies have suggested that coinfection with this virus and HIV leads to slower HIV disease progression. However, this effect remains controversial, as not all studies have agreed with this conclusion, possibly due to differences in the length of HIV infection, definitions of GB virus C "infection" and other factors.

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In an attempt to clarify the relationship between the two viruses, investigators from the Amsterdam Cohort Study carried out a large prospective study of 326 gay men, whose date of HIV seroconversion could be accurately estimated. This design allowed the researchers to assess the dynamics of GB virus C infection over time, and to compare this with the time of HIV seroconversion.

"Rather than a positive effect of GB virus C presence, a negative effect of GB virus C RNA loss on HIV-1 disease progression was found, which disappeared after adjustment for time-updated CD4 count," the authors conclude. "We therefore [hypothesize] that GB virus C RNA persistence depends on the presence of a sufficient number of CD4 cells, and that the CD4 cell decrease associated with HIV-1 disease progression is a cause, not a consequence, of GB virus C RNA loss."

In addition to three monthly measurements of HIV viral load and CD4 counts, the investigators assessed GB virus C infection by testing the blood samples taken shortly after HIV seroconversion and again before January 1996. They tested for active GB virus C infection by measuring RNA levels using the polymerase chain reaction (PCR). Past infection with GB virus C was assessed by testing the samples for the presence of antibodies against the virus's envelope protein-2 (E2).

The men were followed up for a median of eight years. All of the men seroconverted before 1996, or had entered the study between October 1984 and May 1985, after having become infected with HIV.

In the first sample, 137 (42 percent) of the men tested positive for GB virus C RNA, and 134 (41 percent) had antibodies against E2. In the last sample, these values had decreased to 69 (21 percent) and 126 (39 percent) of the men, respectively.

Men with active GB virus C when the first sample was taken had a marginally increased risk of progression to a CD4 count <200 cells/mm3 (hazard ratio [HR] = 1.59; 95 percent confidence interval [CI]: 1.21 to 2.10), AIDS (HR = 1.37; 95 percent CI: 1.02 to 1.81) or death (HR = 1.44; 95 percent CI: 1.06 to 1.96).

This effect was unaffected by adjustment for age at seroconversion, CCR5 coreceptor genotype, antiretroviral therapy, or CD4 count or HIV viral load one year after seroconversion. However, when the change in CD4 cell counts across the follow-up period were taken into account, the effect of GB virus C RNA presence disappeared.

The presence of GB virus C antibodies did not have a significant effect on disease progression. There were also no significant differences in HIV disease progression between the men with active GB virus C infection, those with past infection, and those with no evidence of active or past infection.

"We found no evidence that GB virus C RNA or E2 antibodies had a protective effect with regard to HIV-1 disease progression," the authors conclude.

In contrast, the 78 men who had GB virus C RNA at the first sample, but who had lost it by the last sample were more likely to experience progression to AIDS than those who never had the infection (HR = 2.91; 95 percent CI: 1.93 - 4.40). Similarly, the time of the first CD4 count <200 cells/mm3 was earlier, and survival was reduced in this group of men.

However, when the researchers adjusted their analysis to take CD4 cell counts into account, they saw that the effect of GB virus C RNA loss became much smaller. This suggests that CD4 count is associated with the loss of active GB virus C.

"GB virus C RNA loss was associated with more progressive HIV-1 disease, irrespective of the endpoint of the analysis," they comment. "This effect seemed to correlate most with changes in CD4 count, because the effect became weaker in multivariate analyses in which adjustment was made for this covariate. Because GB virus C RNA can replicate in CD4 cells, the decrease in CD4 cells during the course of HIV-1 infection implies a loss of target cells for GB virus C RNA. This might explain why GB virus C RNA loss is associated with an increased risk of death in HIV-1 infected individuals."

To test the robustness of their conclusions, the researchers repeated their analysis only using data from before the advent of highly active antiretroviral therapy (HAART) in 1996, to exclude any effect of effective antiretroviral therapy. This did not affect their findings. Similarly, neither restricting their analysis to only those patients whose date of seroconversion was accurately known nor adjusting their estimated times of GB virus C RNA loss affected their conclusions.


References

  1. Van der Bij AK, Kloosterboer N, Prins M, et al. GB virus C coinfection and HIV-1 disease progression: The Amsterdam Cohort Study. J Infect Dis 2005;191:678-685.


  
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This article was provided by International Association of Physicians in AIDS Care. It is a part of the publication IAPAC Monthly.
 
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