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GB Virus C: Deterrent to HIV Disease Progression?

Accelerated HIV disease progression and mortality have been associated with some opportunistic coinfections. Could some coinfections possibly have the opposite effect and delay HIV-related mortality? Investigators from 2 independent groups provide provocative data supporting previous observations that coinfection with GB virus C (hepatitis G virus) is associated with a more favorable prognosis in HIV-positive patients.

GB virus C (GBV-C) is a single-stranded RNA virus identified in 1995. Although this virus was originally thought to cause hepatitis, no evidence exists to date that it produces any disease. GBV-C viremia has been reported in 2 percent of healthy blood donors, 15 percent of hepatitis C-positive people, and 35 percent of HIV-positive people. Clearance of viremia, evidenced by the presence of antibody, occurs in more than two thirds of immune-competent hosts.

In the report by Xiang and colleagues, 362 patients, 144 (40 percent) with GBV-C viremia, were followed for a median of 4 years. Subjects entered the cohort from 1988 to 1999. In models adjusted for other known predictors of HIV disease progression, mortality was 3.7-fold higher in patients without GBV-C viremia than in those with viremia. Notably, among the 47 subjects who entered the study after 1995, only 1 death occurred. In vitro experiments demonstrated inhibited HIV replication in cultures coinfected with both HIV and GBV-C.

In the report from Tillmann and colleagues, 197 HIV-positive patients entering clinical care during 1993 and 1994 were classified as GBV-C viremic, GBV-C exposed (i.e., antibody-positive), or GBV-C unexposed. After a mean of 4.2 years, the survival rate was higher, and progression to AIDS was slower, among GBV-C viremic patients than in the other 2 groups. More patients also survived in the GBV-C antibody-positive group than in the GBV-C unexposed group. Analyses limited to the period after subjects developed AIDS also identified reduced mortality associated with GBV-C viremia. HIV RNA levels were higher in GBV-C unexposed patients than in those with GBV-C viremia, but no relation was found between GBV-C viral load and CD4 cell counts. Treatment with potent antiretroviral therapy was associated with increased GBV-C viremia.

Comment: In the natural history of HIV disease, patients with GB virus C infection appear to have a more favorable prognosis than those without. Whether GBV-C is a cause of delayed disease progression or represents a marker for less rapid disease progression is unclear. As the authors of both reports and an editorialist emphasize, clinical application of these data would be premature. Stay tuned for more studies that explore -- and perhaps exploit -- these intriguing findings.

— D Havlir

Published in Journal Watch Infectious Diseases September 20, 2001

Citation(s):

Xiang J et al. Effect of coinfection with GB virus C on survival among patients with HIV infection. N Engl J Med 2001 Sep 6 345 707-714.

• Medline abstract (Free)

Tillmann HL et al. Infection with GB virus C and reduced mortality among HIV-infected patients. N Engl J Med 2001 Sep 6 345 715-724.

• Medline abstract (Free)

Stosor V and Wolinsky S. GB virus C and mortality from HIV infection. N Engl J Med 2001 Sep 6 345 761-762.

• Medline abstract (Free)

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