Impact of heterozygosity for the chemokine receptor CCR5 32-bp-deleted allele on plasma virus load and CD4 T lymphocytes in perinatally human immunodeficiency virus-infected children at 8 years of age.
The CCR5 gene encodes one of the major human immunodeficiency virus type 1 (HIV-1) coreceptors. A 32-bp deletion in this gene (delta ccr5) is associated with relative resistance to disease progression in heterozygous HIV-1-infected persons. The effect of this mutation on virologic and immunologic parameters was determined in a cohort of 45 perinatally HIV-1-infected children prospectively followed after 5 years of age. At a median age of 8.3 years, heterozygous children had significantly lower virus load than homozygous children (median, 3.3 vs. 4.1 log copies/mL, P < .009) and higher percentages of CD4 T cells (median, 26% vs. 17%, P < .07). However, there was no discernible influence of the CCR5 genotype on the percentages of CD8 T cells (P < .27) or on HIV-specific cytotoxic T lymphocyte activities (P < .65). There was a trend for lower rates of progression to AIDS (CDC stage C) in heterozygous children. These data confirm a major role for the CCR5 coreceptor in HIV-1 pathogenesis in children.
Buseyne
F
F
Unité de Virologie et Immunologie Cellulaire, Institut Pasteur, Paris, France.
Janvier
G
G
Teglas
J P
JP
Ivanoff
S
S
Burgard
M
M
Bui
E
E
Mayaux
M J
MJ
Blanche
S
S
Rouzioux
C
C
Rivière
Y
Y
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002648:Child; D005500:Follow-Up Studies; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000635:transmission / Q000821:virology*; D015497:HIV-1; D006579:Heterozygote; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D009154:Mutation; D019713:Receptors, CCR5 / Q000235:genetics*; D017384:Sequence Deletion; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019562:Viral Load
D015488:HIV Antigens; D019713:Receptors, CCR5