Background:  GB virus C (GBV-C) is transmitted by sexual or parenteral exposure and is prevalent among patients receiving blood products. GBV-C is associated with lower HIV viral load and better survival among HIV⁺ patients. Open questions remain concerning the presence and direction of any causal relationship between GBV-C infection, HIV disease markers and HAART.

Methods:  A limited access database obtained from the National Heart, Lung, and Blood Institute, Viral Activation Transfusion Study (VATS), a randomized controlled trial of leuko-reduced (LR) vs. non-LR transfusions to HIV⁺ transfusion-naïve patients was used. Blood samples from 489 subjects were tested for GBV-C markers before and following transfusion. Cox regression, pooled logistic regression models, and inverse probability of treatment weights were used to examine the association between GBV-C co-infection and all-cause mortality in the VATS cohort.

Results:  GBV-C viremia was associated with a significant reduction in mortality among GBV-C co-infected VATS subjects, after adjusting for HAART status, HIV viral load, and CD4 cell count at baseline (HR = 0.42, 95%CI 024 to 0.73). Among a sub-cohort of individuals who were GBV-C^– at baseline (n = 294), each additional unit of blood transfused was associated with an 8% increase in the risk of GBV-C acquisition (95%CI 1.05 to 1.11). Lower baseline HIV viral load and the use of HAART predicted subsequent GBV-C acquisition. GBV-C acquisition from transfusion was associated with lower mortality, adjusting for baseline covariates (HR = 0.22, 95%CI 0.08 to 0.58) and in marginal structural models in which weights were used to control for time-updated co-variates (OR 0.21, 95%CI 0.08 to 0.60).

Conclusions:  GBV-C viremia is associated with lower mortality in HIV⁺ individuals. GBV-C acquisition via transfusion is associated with a significant reduction in mortality in HIV⁺ individuals, controlling for HIV disease markers. These findings confirm previous reports that GBV-C infection inhibits HIV replication in vitro and in vivo, and provide the first evidence that incident GBV-C infection alters mortality in HIV⁺ patients.