832 High Frequency of CCR5-delta32 Homozygosity in HCV-infected, HIV-1 Uninfected Hemophiliacs Results from Resistance to HIV-1 M. Zhang, J. J. Goedert, T. R. O'Brien* Natl Cancer Inst, Rockville, MD
Background: A previous study suggests that the CCR5-Delta32 allele may be an adverse host factor in HCV infection. Because most subjects in that study had hemophilia, we examined this hypothesis in a large cohort of hemophiliacs.
Methods: The Multi-center Hemophilia Cohort Study is a prospective cohort study of U.S. and European patients (pts). CCR5-delta32 genotypes of 1,419 Caucasian subjects were determined by PCR and SSCP. HCV RNA levels were measured with a bDNA assay.
Results: Ninety-six percent (96%) of the subjects were infected with HCV and 72% were infected with HIV-1. Among the1,362 pts who were infected with HCV, the genotypic distribution was very similar to that of all enrolled hemophiliacs and other Caucasian populations; 13 (1.0%) were CCR5-delta32 homozygotes and there was no deviation from Hardy-Weinberg equilibrium (HWE; p > 0.05). Per the previous report, we examined the genotypic distribution among the 358 pts who were infected with HCV, but not HIV-1. Of the HCV- 3.4% were infected, HIV- uninfected hemophiliacs were CCR5- delta32 homozygotes, which is 3-fold higher than expected under HWE (p < 0.0001). However, CCR5-Delta 32 homozygosity was increased among HCV-infected, HIV-uninfected hemophiliacs because only 1/13 (8%) CCR5-delta32 homozygotes were infected with HIV-1, compared to 75% of wild-type pts and 72% of CCR5-delta32 heterozygotes. Furthermore, median HCV RNA levels were similar among CCR5-delta32 homozygotes (2.0 x 106 equivalents/ml) and wild-type pts (3.1 x 106 equivalents/ml; p > 0.05).
Conclusion:The CCR5-delta32 allele is not an adverse host factor in HCV infection. The previously reported increased frequency of CCR5-delta32 homozygosity in HCV-infected, HIV-1-uninfected hemophiliacs is due to the protective role of this genotype against HIV-1 infection.
