Kaslow RA, Tang J, Naik E, Karita E, Allen S; Conference on Retroviruses and Opportunistic Infections.

Program Abstr 8th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 8th 2001 Chic Ill. 2001 Feb 4-8; 8: 57 (abstract no. 45B).

Univ of Alabama at Birmingham.

Background: Polymorphisms in CCR2, CCR5 and HLA class I genes affect the course of HIV-1 infection but could do so differently in Caucasians and Africans because of distinctive genetic background, HIV-1 subtypes and other host and environmental factors. We evaluated relationships of these genes to disease progression in Rwandans as compared with relationships reported principally in Caucasians. Methods: 202 Rwandan women were infected with HIV-1 at or soon after enrollment in a gynecologic clinic in 1986, untreated, and staged after >11 years of follow-up by modified clinical/immunologic (C/I) criteria [Lifson et al Ann Int Med 1995;122: 262] for disease progression: - C/I >11 y (54), + C/I > or = 11 y (108), ++ C/I <11 y (25), AIDS/death <6 y (15). Sequence-specific techniques were used to type for CCR2 -64V/I, SNPs at CCR5 promoter positions 303-627-676-927, SDF1-3'A, and HLA-A,-B,and -C alleles. By logistic regression for 4-category uni- and multivariable odds ratio (OR), we examined the strength and independence of contributions of candidate polymorphisms to disease progression. P values shown correspond to the multivariable pOR. Results: HLA-A or -B locus homozygosity (A/B hmz) and each of 6 polymorphisms in class I HLA and CCR closely related to those reported elsewhere to modify disease progression were also independently and significantly (p = 0.001 0.03) associated in Rwandans: A/B hmz (2.2), B*3502- 4 (8.5) B*53 (2.8), B*57 (0.80), A*29-Cw*07 (8.4), B*1510-Cw*03 (3.8), and CCR2-64I-CCR5 (promoter)-A-C-A-C hmz (5.1). A model summarizing these effects strongly predicted outcome in the population (p < 0.0001). Homozygotes for the CCR2-64I-CCR5 (promoter)-A-C-A-T haplotype also showed a non-significant trend toward protection (0.65). SDF1-3'A showed no effect. Conclusions: Genetic determinants closely related to those associated with prognosis of HIV-1 infection primarily in Caucasians appear to regulate progression similarly in Rwandans carrying virus of a different clade. To that extent, immunomodulatory interventions targeting mechanisms governed by these genes may have advantageously broad applications across populations.

Publication Types:

• Meeting Abstracts

Keywords:

• Acquired Immunodeficiency Syndrome
• African Continental Ancestry Group
• Alleles
• Disease Progression
• European Continental Ancestry Group
• Female
• Genes, MHC Class I
• HIV Infections
• HIV-1
• Haplotypes
• Humans
• Polymorphism, Genetic
• Polymorphism, Single Nucleotide
• Receptors, CCR5
• Receptors, Chemokine
• genetics
• immunology

Other ID:

• GWAIDS0006329

UI: 102243825

From Meeting Abstracts