8th Conference on Retroviruses and Opportunistic Infections Chicago, IL - February 4 - 8, 2001

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:192 (abstract no. 499)

Woitas RP, Ahlenstiel G, Brackmann HH, Matz B, Rockstroh JK, Spengler U; 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-delta32) (present in 1% of a Caucasian population) is associated with resistance to HIV-1 infection. However, the role of the CCR5-delta32 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-delta32 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-delta32/CCR5-delta32 vs. CCR5-delta/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, X2 and 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. Delta32/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 the delta32/delta32 genotype, while homozygous patients were completely absent in both HIV-infected groups (p<0.001). Furthermore, the distribution of the delta32/delta32 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). The delta32/delta32 homozygous patients had significantly higher HCV loads than the WT/WT or the heterozygous delta32/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-delta32 mutation is protective against HIV infection. However, the increased frequency of delta32/delta32 genotypes among patients with HCV infection together with increased HCV loads in CCR5-delta32 homozygotes suggests unfavourable effects of this mutation for the course of HCV infection.

Keywords: AEGIS, Hepacivirus, Viral Load, HIV-1, HIV Infections, Genotype, Mutation, Homozygote, Hepatitis C Antibodies, Heterozygote, Anti-HIV Agents, Alleles, Reverse Transcriptase Inhibitors, Human, genetics, AIDS

2001-02-04
499

Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.