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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Effects of CCR5-δ32 and CCR2-641 alleles on disease progression of perinatally HIV-1-infected children: An international meta-analysis
AIDS, Volume 17, No. 11, Year 2003
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Description
Objective: Among perinatally infected children, the effects of certain alleles of the CCR5 and CCR2 genes on the rate of disease progression remain unclear. We addressed the effects of CCR5-A32 and CCR2-641 in an international meta-analysis. Methods: Genotype data were contributed from 10 studies with 1317 HIV-1-infected children (7263 person-years of follow-up). Time-to-event analyses were performed stratified by study and racial group. Endpoints included progression to clinical AIDS, death, and death after the diagnosis of clinical AIDS. The time-dependence of the genetic effects was specifically investigated. Results: There was large heterogeneity in the observed rates of disease progression between different cohorts. For progression to clinical AIDS, both CCR5-A32 and CCR2-641 showed overall non-significant trends for protection [hazard ratios 0.84, 95% confidence interval (Cl) 0.58-1.23; and 0.87, 95% Cl 0.67-1.14, respectively]. However, analyses of survival showed statistically significant time-dependence. No deaths occurred among CCR5-A32 carriers in the first 3 years of life, whereas there was no protective effect (hazard ratio 0.95; 95% Cl 0.43-2.10) in later years (P = 0.01 for the time-dependent model). For CCR2-641, the hazard ratio for death was 0.69 (95% Cl 0.39-1.21) in the first 6 years of life and 2.56 (95% Cl 1.26-5.20) subsequent years (P < 0.01 for the time-dependent model). CCR5-Δ32 and CCR2-641 offered no clear protection after clinical AIDS had developed. Conclusion: The CCR5-A32 and CCR2-641 alelles are associated with a decreased risk of death among perinatally infected children, but only for the first years of life. © 2003 Lippincott Williams & Wilkins.
Authors & Co-Authors
Ioannidis, John P.A.
Greece, Ioannina
Faculty of Medicine
Greece, Heraklion
Foundation for Research and Technology-hellas
United States, Washington, D.c.
The George Washington University School of Medicine and Health Sciences
Contopoulos-Ioannidis, Despina G.
Greece, Ioannina
Faculty of Medicine
United States, Washington, D.c.
The George Washington University School of Medicine and Health Sciences
Rosenberg, Philip S.
United States, Bethesda
National Institutes of Health Nih
Goedert, James Jerome
United States, Bethesda
National Institutes of Health Nih
De Rossi, Anita
Italy, Padua
Università Degli Studi Di Padova
Español, Theresa
Spain, Barcelona
Hospital Universitari Vall D'hebron
Frenkel, Lisa M.
United States, Seattle
University of Washington
Mayaux, Marie Jeanne
France, Paris
Inserm
Newell, Marie Louise
United Kingdom, London
University College London
Pahwa, Savita G.
United States, New York
Nyu Grossman School of Medicine
Rousseau, Christine M.
United States, Seattle
Va Puget Sound Health Care System
SCARLATTI, GABRIELLA
Italy, Milan
Irccs Ospedale San Raffaele
Sei, Shizuko S.
United States, Bethesda
National Institutes of Health Nih
O'Brien, Thomas R.
United States, Bethesda
National Institutes of Health Nih
Statistics
Citations: 43
Authors: 14
Affiliations: 13
Identifiers
Doi:
10.1097/00002030-200307250-00007
ISSN:
02699370
Research Areas
Environmental
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Design
Cohort Study
Study Approach
Systematic review