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 ty pe 1 (HIV-1) coreceptors. A 32-bp deletion in this gene (Delta ccr5) i s associated with relative resistance to disease progression in hetero zygous HIV-1-infected persons. The effect of this mutation on virologi c and immunologic parameters was determined in a cohort of 45 perinata lly HIV-1-infected children prospectively followed after 5 years of ag e. At a median age of 8.3 years, heterozygous children had significant ly 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 th e CCR5 genotype on tee percentages of CD8 T cells (P < .27) or on HIV- specific cytotoxic T lymphocyte activities (P < .65). There was a tren d 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.