159lb Persistent GBV-C virus Type C (GBV-C) Infection is Associated with Decreased Risk of Death in HIV-seroconvertors in the Multicenter AIDS Cohort Study (MACS) C. Williams*1, D. Klinzman2, T. Yamashita3, J. Xiang2, P. Polgreen2, C. Rinaldo4, C. Liu5, J. Phair6, J. Margolick7, D. Zdunek8, G. Hess8, J. Stapleton2 1Epidemiology, NIAID/NIH/DHHS, Bethesda, MD; 2Iowa City VA Med Cntr, U of Iowa, Iowa City, IA; 3Johns Hopkins, Bloomberg SPH, Baltimore, MD; 4U of Pittsburgh, Pittsburgh, PA; 5UCLA, Los Angeles, CA; 6Northwestern U, Chicago, IL; 7Johns Hopkins Sch of Med, Baltimore, MD; and 8Roche Laboratories, Penzburg, Germany
Background: GBV-C is not known to cause disease, replicates in lymphocytes, inhibits HIV replication in vitro, and has been associated with a decreased risk of death among HIV positive persons in some, but not all, studies. Previous studies based on convenience samples could not rule out bias due to unknown durations of HIV and GBV-C infection.
Methods: Stored plasma obtained from MACS participants with incident HIV infection 1 - 1 1/2 years (early visit; N=271) and 5-6 years (late visit; N=138) after HIV seroconversion were tested for GBV-C infection. Viremia was measured by GBV-C RNA RT-PRC (RNA), and prior GBV-C infection by anti-GBV-C E2 antibodies (Ab).
Results: At the early visit, 39% were GBV-C RNA pos, an additional 46% were GBV-C RNA neg but E2 Ab pos, 1% were positive for RNA and Ab, and 14% were neg for both RNA and Ab. Acquisition of GBV-C between visits was rare (N=1); however, 12 (8.7%) of the 138 men tested at both visits cleared GBV-C viremia between visits. GBV-C RNA status at the early visit was not associated with a difference in survival. In contrast, GBV-C RNA at the late visit was strongly associated with survival: compared to men who were RNA pos at both visits, men who were GBV-C RNA negative at both visits were 2.43 times more likely to die (95% CI 1.2 - 5.2; P<0.01) and those who cleared GBV-C infection between visits were 5.87 times more likely to die (95% CI 2.2 - 15.4; P<0.01). The mean rates of CD4 cell loss per year in those persistently positive, persistently negative, and who cleared GBV-C RNA were 26, 37, and 107 cells per year, respectively. The median duration of follow-up, date of seroconversion, use of HIV therapy, median log 10 HIV-RNA values and prevalence of CCR5 32 polymorphisms did not vary by GBV-C status.
Conclusions: GBV-C viremia assessed 5-6 years after HIV seroconversion was a strong predictor of survival, and loss of GBV-C predicted a higher risk of death. Mis-classification of those who cleared GBV-C as "positive", based on the early visit, proved important as there was an increased risk of death with the clearance of GBV-C. GBV-C infection has a high attributable benefit in HIV infection, since both the prevalence of GBV-C and size of its protective effect were high. Understanding the mechanisms for the interaction between GBV-C and HIV may provide insights into ways to control HIV disease progression.
