Should GB virus be used as a therapeutic vaccine to slow HIV progression?

Acquisition of GB virus C (GBV-C) is associated with a 78% reduction in mortality risk for people with AIDS, investigators report in the online edition of Clinical Infectious Diseases. The beneficial effects of GBV-C infection (often incorrectly called hepatitis G virus) were significant even after controlling for CD4 cell count, HIV viral load and use of antiretroviral therapy, leading an expert in infectious diseases to ask whether GB virus C ought to be considered as a therapeutic vaccine.

Dr David Gretch, the author of an editorial accompanying the study, believes the results settle any doubts about the protective effects of GBV-C virus infection in HIV disease. He comments: “GBV-C viremia is associated with protective effects in persons with HIV, and the idea of a therapeutic GBV-C biovaccine in persons with HIV is an important one to consider, especially in resource poor countries where AIDS death rates remain high.” 

GBV-C is a non-dangerous infection that is transmitted in similar ways to HIV. An earlier meta-analysis of studies involving 1294 HIV-positive people showed that co-infection with GBV-C was associated with a 59% reduction in the relative risk of death. This finding is consistent with laboratory research which indicate that GBV-C induces cytokines that inhibit HIV, lower T-cell activation, block IL-2 mediated CD4 T-cell proliferation and reduce expression of the HIV entry receptors, CCR5 and CXCR4.

Despite these results, many doctors remain unconvinced of the beneficial effects of infection with this virus. In particular, the effect of incident GBV-C infection on disease progression in people already infected with HIV is uncertain.

Investigators from the Viral Activation Transfusion Study (VATS) believed that their cohort of people with advanced HIV disease provided an ideal population in which to examine the impact of prevalent and incident GBV-C infection on all-cause mortality.

Blood samples obtained from the study participants before and after blood transfusion, were retrospectively tested for GBV-C antibodies and RNA. The investigators were therefore able to accurately determine whether participants were infected with this virus at baseline, or acquired the infection during follow-up. The study was conducted in 1996-97, shortly after the introduction of effective antiretroviral therapy.

A total of 489 people, all of whom had AIDS, were included in the authors’ analyses. At baseline, 60% of people were negative for both GBV-C antibodies and RNA, 33% had antibodies to the infection and 7% had detectable GBV-C RNA. Participants were followed for a median of 8.4 months. A total of 267 people (55%) died and a further 9% withdrew from the study or were lost to follow-up.

Survival was significantly better for people with detectable GBV-C at baseline compared to those who did not (p = 0.02). The association between GBV-C viraemia and improved survival remained significant after adjusting for several important baseline characteristics associated with outcomes in people with HIV, including CD4 cell count, HIV viral load and use of combination antiretroviral therapy (adjusted HR = 0.42; 95% CI, 0.24-0.73).

A total of 39 people (13%) acquired GBV-C infection during the course of the study. Even after adjusting for other prognostic factors, people with GBV-C RNA after incident infection had a substantial reduction in their mortality risk (adjusted HR = 0.22; 95% CI, 0.08-0.58) compared to the people who remained GBV-C RNA-negative.

“We found that GBV-C viremia is associated with lower mortality in HIV-infected patients, after adjusting for baseline HIV viral load, CD4 count and HAART status,” write the investigators. “In addition, we found a significant reduction in mortality associated with incident GBV-C infection during follow-up…even after controlling for time-updated HIV disease markers.”

Dr Gretch believes that the study’s findings are potentially of huge significance.

He stresses that GBV-C is so safe in humans that blood donations in the US are not screened for its presence, and also notes that the virus is “a natural bio-antagonist for HIV.”

“Still today,” he concludes, “the death rate from HIV remains enormous, especially in resource poor countries, and we have yet to see a trial of GBV bio-vaccination in HIV-infected populations with high death risk…it’s time for an interventional GBV biotherapy therapy study in persons with life-threatening HIV infections.”

Vahidnia F et al. Acquisition of GB virus type C (HGV) and lower mortality in patients with advanced HIV disease. Clin Infect Dis, online edition, 2012.

Gretch D Advocating the concept of GBV biotherapy against AIDS. Clin Infect Dis, online edition, 2012.