 |
|
CCR5 Chemokine Receptor Variant in HIV-1 Mother-to-Child Transmission and Disease Progression in Children
Micheline Misrahi, MD, PhD;
Jean-Paul Teglas, MS;
Nicole N'Go, PhD;
Marianne Burgard, MD;
Marie-Jeanne Mayaux;
Christine Rouzioux, PhD;
Jean-François Delfraissy, MD;
Stéphane Blanche, MD;
for the French Pediatric HIV Infection Study Group
JAMA. 1998;279:277-280.
Context.— Studies suggest that adults with the CCR5 32 deletion are less likely to become infected with the human immunodeficiency virus (HIV) and to develop HIV-related disease progression, but the effect of the mutation in children is not known.
Objective.— To study the effect of the CCR5 chemokine receptor mutant allele on mother-to-child transmission of HIV type 1 (HIV-1) and subsequent disease progression in infected children.
Design.— Multicenter, prospective study of infants born to mothers seropositive for HIV-1.
Setting.— A total of 52 medical centers participating in the French Pediatric HIV Cohort studies.
Participants.— The CCR532 deletion was studied in 512 non-African children, born between 1983 and 1996 to HIV-1–infected mothers. Among them, 276 children were infected and 236 were not.
Main Outcome Measures.— HIV-1 infection status and, in infected children followed up since birth, incidence of category B and C disease events and severe immunosuppression as defined in the new pediatric Centers for Disease Control and Prevention (CDC) classification, according to CCR5 genotype.
Results.— The 32–base pair deleted allele was detected at a frequency of 0.05. Only 1 infant, not infected by HIV-1, was homozygous for the 32 deletion. The 49 heterozygous children (9.6% of the total; 95% confidence interval [CI], 7.1-12.2) were equally distributed into the infected (9.8%) and uninfected (9.3%) groups. The incidence of stage C symptoms in heterozygous infected children was 9% at 36 months vs 28% in children homozygous for the normal allele (P<.004). The proportion of children at 8 years old with no stage B or C symptoms was 49% for heterozygous children and 11% for children homozygous for the normal allele (P<.003). The progression of severe immune deficiency (CD4 <15%, CDC stage 3) was also significantly different between the 2 groups (P<.001).
Conclusions.— Heterozygosity for the CCR532 deletion does not protect children from infection by the maternal virus but substantially reduces the progression of the disease in HIV-1–infected children.
From the Laboratory of Hormonology and Molecular Biology (Dr Misrahi), the Institut National de la Santé et de la Recherche Médicale, Unite 292: Public Health, Epidemiology, and Human Reproduction (Mr Teglas and Ms Mayaux), and the Department of Internal Medicine (Dr Delfraissy), Hôpital de Bicêtre, Le Kremlin Bicêtre, France; the Laboratory of Virology (Drs N'Go, Burgard, and Rouzioux) and the Unit of Pediatric Immunology and Hematology (Dr Blanche), Hôpital Necker Enfants Malades, Paris, France.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED LETTER
CCR5 Genotype and Mother-to-Child HIV Transmission
Henry Rascoff and Stéphane Blanche
JAMA. 1998;279(24):1953.
EXTRACT
| FULL TEXT
RELATED ARTICLE
Chemokine Receptors and Genetic Variability: Another Leap in HIV Research
Thomas R. O'Brien and James J. Goedert
JAMA. 1998;279(4):317-318.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Potent, Broad-Spectrum Inhibition of Human Immunodeficiency Virus Type 1 by the CCR5 Monoclonal Antibody PRO 140
Trkola et al.
J. Virol. 2001;75:579-588.
ABSTRACT
| FULL TEXT
A Polymorphism in the Regulatory Region of the CC-Chemokine Receptor 5 Gene Influences Perinatal Transmission of Human Immunodeficiency Virus Type 1 to African-American Infants
Kostrikis et al.
J. Virol. 1999;73:10264-10271.
ABSTRACT
| FULL TEXT
Differential Tropism and Replication Kinetics of Human Immunodeficiency Virus Type 1 Isolates in Thymocytes: Coreceptor Expression Allows Viral Entry, but Productive Infection of Distinct Subsets Is Determined at the Postentry Level
Pedroza-Martins et al.
J. Virol. 1998;72:9441-9452.
ABSTRACT
| FULL TEXT
CCR5 Genotype and Mother-to-Child HIV Transmission
Rascoff and Blanche
JAMA 1998;279:1953-1953.
FULL TEXT
CCR-5 Mutation May Keep HIV-Infected Children Well
AIDS Clin Care 1998;1998:3-3.
FULL TEXT
CCR5 Mutations in Children of HIV-infected Mothers
JWatch Infect. Diseases 1998;1998:10-10.
FULL TEXT
GENETIC PROTECTION AGAINST HIV
JWatch General 1998;1998:2-2.
FULL TEXT
Chemokine Receptors and Genetic Variability: Another Leap in HIV Research
O'Brien and Goedert
JAMA 1998;279:317-318.
FULL TEXT
|
