Title

Fraction of Cases of Acquired Immunodeficiency Syndrome Prevented by the Interactions of Identified Restriction Gene Variants

Authors

M. J. Silverberg, Johns Hopkins University
M. W. Smith, National Cancer Institute at Frederick
Joan S. Chmiel, Northwestern University
Roger Detels, University of California - Los Angeles
Joseph Margolick, Johns Hopkins University
Charles Rinaldo, University of Pittsburgh
Stephen J. O'Brien, National Cancer Institute at FrederickFollow
A. Muñoz, Johns Hopkins University

Document Type

Article

Publication Date

2-1-2004

Publication Title

American Journal of Epidemiology

Keywords

Acquired immunodeficiency syndrome, Chemokines, Cytokines; Epidemiologic methods, HIV-1, HLA antigens, Receptors, Chemokine

ISSN

0002-9262

Volume

159

Issue/No.

3

First Page

232

Last Page

241

Abstract

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)-Δ32 and C-C chemokine receptor 2 (CCR2)-64I (relative hazard = 0.44); 2) interleukin 10 (IL10)-+/+ in combination with CCR5-Δ32 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.

Comments

©2004 by the Johns Hopkins Bloomberg School of Public Health

Additional Comments

National Cancer Institute grant and contract #s: UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041, NO1-CO-12400

NSUWorks Citation

Silverberg, M. J.; M. W. Smith; Joan S. Chmiel; Roger Detels; Joseph Margolick; Charles Rinaldo; Stephen J. O'Brien; and A. Muñoz. 2004. "Fraction of Cases of Acquired Immunodeficiency Syndrome Prevented by the Interactions of Identified Restriction Gene Variants." American Journal of Epidemiology 159, (3): 232-241. https://nsuworks.nova.edu/cnso_bio_facarticles/578

ORCID ID

0000-0001-7353-8301

ResearcherID

10.1093/aje/kwh036