Epidemiology

Virus formerly known as hepatitis G may reduce HIV mortality

Last Updated: 2012-07-24 17:40:17 -0400 (Reuters Health)

By Will Boggs MD

NEW YORK (Reuters Health) - In patients with HIV infection, coinfection with GB virus C (GBV-C), formerly called hepatitis G virus, is linked with significantly lower mortality, a new study shows.

"Since approximately 25% of HIV-infected people have GBV-C co-infection, co-infection may have considerable impact on the HIV epidemic," lead investigator Dr. Farnaz Vahidnia from Blood Systems Research Institute in San Francisco told Reuters Health in an email. "Understanding how GBV-C infection alters HIV disease course may identify novel approaches for developing therapy for HIV."

In a July 2 online paper in Clinical Infectious Diseases, Dr. Vahidnia and colleagues note that GBV-C is a nonpathogenic human virus transmitted sexually, parenterally, and vertically. It's been linked with prolonged survival among HIV-infected patients in some, but not all studies.

In vitro, GBV-C induces an HIV-inhibitory cytokine profile, decreases T cell activation, blocks IL-2-mediated CD4 T cell proliferation, and reduces expression of the HIV entry receptors CCR5 and CXCR4.

In their new analysis, Dr. Vahidnia and colleagues examined the effect of preexisting GBV-C infection and incident GBV-C infection via transfusion on all-cause mortality in 489 HIV-infected participants in the Viral Activation Transfusion Study (VATS).

During a median follow-up of 8.4 months (IQR, two to 22 months), 267 study subjects died (55%).

All-cause mortality was significantly lower among patients with pre-existing GBV-C viremia than among patients who were GBV-C RNA-negative at baseline, the authors report. The difference persisted after adjusting for baseline CD4 cell counts, HIV viral load, and highly active antiretroviral therapy (HAART) status.

Among patients who were GBV-C-negative at baseline, acquisition of GBV-C was associated with a 78% reduction in mortality, which also persisted after adjusting for other factors.

"To our knowledge," the researchers say, "this is the first report showing a survival benefit of incident GBV-C infection among patients who were infected with HIV prior to GBV-C acquisition."

In a Cox regression model, mortality or virological failure risk was not significantly different between GBV RNA-positive and -negative patients who were receiving HAART at baseline or who started HAART during follow-up, although there was a trend toward lower virological failure associated with GBV-C infection regardless of HAART status.

"One of the most crucial factors in establishing a causal relationship is the temporal sequence of the events, i.e. GBV-C viremia and changes in HIV disease markers in our study," Dr. Vahidnia said. "There is difficulty in applying Koch's postulates for this virus, since it is not easily grown in vitro and since experimental infection is not easily accomplished in a controlled setting."

"An important strength of our study is that we were able to demonstrate a reduction in mortality in HIV patients with 'recent' GBV-C infection (incident viremia), while properly controlling for changes in HIV disease markers over time using new statistical methods (marginal structural models)," Dr. Vahidnia explained. "These methods enable us to analyze data from observational studies in a way that resembles randomized clinical trials."

"Given the consistency in our findings using various analytical approaches, we are confident that this relationship is not just a coincidence in the general sense of the term, but rather a real property of the co-infection," Dr. Vahidnia concluded.

In an editorial, Dr. David Gretch from University of Washington in Seattle writes, "GBV-C appears to be safe in humans, and is a natural bio-antagonist of HIV."

"It is difficult to estimate how many years of human life GBV-C has already saved," Dr. Gretch says. "Still, today, the death rate from HIV remains enormous, especially in resource poor countries, and we have yet to see a trial of GBV-C bio-vaccination in HIV-infected populations with high death risk."

"Similar to the days of smallpox," the editorial concludes, "it's time for an interventional GBV biotherapy study in persons with life-threatening HIV infections."

SOURCE: http://bit.ly/MGgs19

Clin Infect Dis 2012.