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Genetic polymorphisms in CX3CR1 predict HIV-1 disease progression in children independently of CD4+ lymphocyte count and HIV-1 RNA load.

Singh KK, Hughes MD, Chen J, Spector SA

Department of Pediatrics, Division of Infectious Diseases, University of California, San Diego, La Jolla, California 92093-0672, USA.

BACKGROUND: The impact of CX3CR1 polymorphisms on human immunodeficiency virus type 1 (HIV-1) pathogenesis is controversial, with conflicting reports of their role in disease progression in HIV-1-infected adults. METHODS: A cohort of 1055 HIV-1-infected children were genotyped for 2 CX3CR1 polymorphisms, V/I249 and T/M280, and their impact on HIV-1-related disease progression, including central nervous system (CNS) impairment, was evaluated. RESULTS: Children with the CX3CR1 I/I249 genotype experienced more-rapid disease progression (I/I249 vs. V/V249: relative hazard [RH], 2.19 [95% confidence interval {CI}, 1.30-3.68], P=.003; I/I249 vs. V/I249: RH, 1.77 [95% CI, 1.00-3.14], P=.05) and a trend toward more CNS impairment (I/I249 vs. V/V249: RH, 2.19 [95% CI, 1.00-4.78], P=.049; I/I249 vs. V/I249: RH, 2.02 [95% CI, 0.85-4.83], P=.11). Children with the V249-T280 haplotype experienced significantly less disease progression (RH, 0.42 [95% CI, 0.24-0.73]; P=.002) and CNS impairment (RH, 0.39 [95% CI, 0.39-0.22]; P=.001). Of note, these effects remained significant after CD4+ lymphocyte count and plasma HIV-1 RNA load at baseline were adjusted for and in a longitudinal, multivariate analysis. CONCLUSIONS: CX3CR1 genotypes and haplotypes impact HIV-1 disease progression independently of CD4+ lymphocyte count and plasma HIV-1 RNA load, suggesting that the fundamental role of CX3CR1 in the alteration of disease progression might be the recruitment of immunomodulatory cells responsible for the control of HIV-1.

Published 4 May 2005 in J Infect Dis, 191(11): 1971-80.
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