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Session 51 Poster Session Impact of Host Genetics on Viral Transmission and Disease Progression Session Time: 4:30-6:30 pm Room 4E-F

324-W. Protective Effect of IL4 -589T Polymorphism on HIV-1 Disease Progression: Relationship with Viral Load E. E. Nakayama*1, L. Meyer2, A. Iwamoto3, A. Persoz2, Y. Nagai4, C. Rouzioux5, J-F. Delfraissy2, for the SEROCO Study Group, P. Debre6, D. McIlroy6, I. Theodorou6, and T. Shioda1 1Res. Inst. for Microbial Diseases, Osaka Univ., Japan; 2Hosp. Bicêtre, Kremlin-Bicêtre, France; 3Inst. of Med. Sci., Univ. of Tokyo, Japan; 4Natl. Inst. of Infectious Diseases, Tokyo, Japan; 5Hosp. Necker, Paris, France; and 6Hosp. Pitie-Salpetriere, Paris, France Background: IL4 down-regulates CCR5 expression and thus inhibits replication of HIV-1 R5 virus in human T cells and macrophages. On the other hand, IL4 up-regulates the expression of CXCR4 and enhances the replication of X4 variants. IL4 -589T allele is a single nucleotide polymorphism with a C to T exchange at position -589 upstream from the open reading frame of the IL4 gene. This SNP is associated with increased promoter activity for IL4 transcription and influences IgE serum levels. Methods: To determine the influence of this allele on HIV-1 disease, we analyzed HIV-1 disease progression and serum viral load according to the IL4 promoter genotype in 427 Caucasian patients with a known date of seroconversion, who were followed in the SEROCO cohort between 1988 and 1996. Results: The frequency of the IL4 -589T allele was 0.15 in 427 patients. Serum viral load was 0.20 log lower during the 6-24 month plateau phase after seroconversion in patients with IL4 -589T allele than in those without this allele (median of 3.85 and 4.05 log10 copies/mL, respectively, Wilcoxon test, p=0.02). Kaplan-Meier survival curves showed a slower progression to clinical AIDS in carriers of IL4 -589T (log-rank test, p=0.04). After adjustment for early serum viral load, the strength of the association was greatly diminished. On the other hand, adjustment for CCR5delta32 and the M280 mutation in CX3CR1 did not influence the results. Conclusions: These results suggest that IL4 -589T allele protects against HIV-1 disease progression due in part to a reduction in viral load.

©2002 9th Conference on Retroviruses and Opportunistic Infections