Am J Epidemiol 2004; 159:232-241.
Copyright © 2004 by the Johns
Hopkins Bloomberg School of Public Health
ORIGINAL CONTRIBUTIONS |
Fraction of Cases of Acquired Immunodeficiency Syndrome Prevented by the Interactions of Identified Restriction Gene Variants
1 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
2 Basic Research Program, Science Applications International Corporation, Frederick, MD.
3 Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
4 Department of Epidemiology, School of Public Health, University of California, Los Angeles, Los Angeles, CA.
5 Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
6 Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
7 Laboratory of Genomic Diversity, National Cancer Institute–Frederick, Frederick, MD.
Previous research has demonstrated isolated effects of host genetic factors on the progression of human immunodeficiency virus type 1 (HIV-1) infection. In this paper, the authors present a novel use of multivariable methods for estimating the prevented fraction of acquired immunodeficiency syndrome (AIDS) cases attributable to six restriction genes after accounting for their epidemiologic interactions. The methods presented will never yield a prevented fraction above 1. The study population consisted of a well-characterized cohort of 525 US men with HIV-1 seroconversion documented during follow-up (1984–1996). On the basis of a regression tree approach using a Cox proportional hazards model for times to clinical AIDS, the combinations of genes associated with the greatest protection, relative to the lack of a protective genotype, consisted of: 1) C-C chemokine receptor 5 (CCR5)-
32 and C-C chemokine receptor 2 (CCR2)-64I (relative hazard = 0.44); 2) interleukin 10 (IL10)-+/+ in combination with CCR5-32 or CCR2-64I (relative hazard = 0.45); and 3) IL10-+/+ in combination with stromal-derived factor (SDF1)-3 'A and CCR5 promoter P1/~P1 (relative hazard = 0.37). Overall, 30% of potential AIDS cases were prevented by the observed combinations of restriction genes (95% confidence interval: 7, 47). However, the combined effect was confined to the first 4 years following HIV-1 seroconversion. Additional research is needed to identify AIDS restriction genes with stronger and long-lasting protection to better characterize the genetic epidemiology of HIV-1.
acquired immunodeficiency syndrome; chemokines; cytokines; epidemiologic methods; HIV-1; HLA antigens; receptors, chemokine
Abbreviations: Abbreviations: AIDS, acquired immunodeficiency syndrome; CCR2, C-C chemokine receptor 2; CCR5, C-C chemokine receptor 5; CCR5P, C-C chemokine receptor 5 promoter; CI, confidence interval; HIV-1, human immunodeficiency virus type 1; HLA, human leukocyte antigen; IL10, interleukin 10; MACS, Multicenter AIDS Cohort Study; PF, prevented fraction; RH, relative hazard; SDF1, stromal-derived factor.
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