499   CCR5-D32 Mutation— Protective Against HIV, but Bad for Hepatitis C Virus?

R. P. Woitas*, G. Ahlenstiel, H. H. Brackmann, B. Matz, J. K. Rockstroh*, and U. Spengler.
Inst. of Experimental Hematology, Virology, Univ. of Bonn, Germany.

Background:CCR5 has been identified as the major co-receptor for the entry of M-tropic variants of HIV-1. Polymorphisms in the CCR5 gene can modulate the natural history of HIV. Indeed homozygosity of a 32-base- pair (bp) deletion (CCR5-D32) (present in 1% of a Caucasian population) is associated with resistance to HIV-1 infection. However, the role of the CCR5-D32 mutant allele for other infections such as hepatitis C virus (HCV) has not been defined yet.

Methods:We determined the frequency of the mutant CCR5-D32 allele by PCR in a cohort of 151 anti-HCV- positive, 105 anti-HIV-positive and 130 HIV/HCV-coinfected patients. Patients were stratified according to their CCR5 genotypes (CCR5-D32/CCR5-D32 vs. CCR5-D/wild-type (WT) vs. WT/WT) and compared with respect to HIV and HCV viral loads, aminotransferases, CD4 and CD8 cell counts. Statistical analysis was performed using ANOVA,C²and non-parametric tests.

Results:The CCR5 WT/WT genotype was present in 116/151 (76.8%), 86/105 (81.9%), and 97/130 (74.6%) of the patients with HCV single, HIV single and HIV/HCV double infection, respectively.D32/WT heterozygotes were found in 25/151 (16.6%), 19/105 (18.1%), and 33/130 (25.4%) of patients in each group, respectively. 10/ 151 (6.6%) patients with HCV exhibited theD32/D32 genotype, while homozygous patients were completely absent in both HIV-infected groups (p < 0.001). Furthermore, the distribution of theD32/D32 genotype in anti- HCV-positive patients was threefold higher than predicted by the Hardy-Weinberg equation (p < 0.001). HCV loads were significantly higher in HIV/HCV-coinfected patients of all subgroups than in patients with HCV alone (p < 0.05). TheD32/D32 homozygous patients had significantly higher HCV loads than the WT/WT or the heterozygousD32/WT genotype (p < 0.01). Aminotransferases did not vary with respect to the CCR5 genotype but were significantly higher in patients with HIV/HCV coinfection (p < 0.05).

Conclusions:Our data confirm that homozygosity for the CCR5-D32 mutation is protective against HIV infection. However, the increased frequency ofD32/D32 genotypes among patients with HCV infection together with increased HCV loads in CCR5-D32 homozygotes suggests unfavourable effects of this mutation for the course of HCV infection.