[20] CCR5 HAPLOTYPES ASSOCIATED WITH ALTERED RATES OF HIV-1 VERTICAL TRANSMISSION AND PROGRESSION TO DISEASE IN CHILDREN

1st International AIDS Society Conference on HIV Pathogenesis and Treatment

Buenos Aires, Argentina - July 8-11, 2001

[TITLE:] CCR5 HAPLOTYPES ASSOCIATED WITH ALTERED RATES OF HIV-1 VERTICAL TRANSMISSION AND PROGRESSION TO DISEASE IN CHILDREN

[AUTHOR(S):] Mangano A, Gonzalez E, Catano G, Bologna R, Ahuja S, Sen L
Hospital Nacional De Pediatría "Garrahan", BS. AS. Argentina, University of Texas, Health Science Center, San Antonio,USA. Capital Federal, Buenos Aires, Argentina

IAS Conf HIV Pathog Treat 2001 Jul 8-11;1st: Abstract No. 20

[ABSTRACT:] Genetic variation in CC chemokine receptor 5 (CCR5), the major coreceptor for HIV-1 cell entry, has been associated with differences in susceptibility to infection as well as disease progression. The aim of this study was to determine the contribution of CCR5 genotypes in HIV-1 mother-to-child transmission and progression to AIDS in infected children.The study design was an academic pediatric hospital center-based study. CCR5 haplotypes in 649 (347 infected and 302 uninfected) children exposed perinatally to HIV-1 was determined using PCR-RFLP and molecular beacon assays. Using an evolutionary-based classification described previously by us, CCR5 haplotypes were grouped into seven human haplogroups (HH)-A, -B, -C, -D, -E, -F (F1 and F2), -G (G1 and G2). Five haplotype pairs influenced the risk of vertical transmission, including three HHE-containing haplotype pairs that increased susceptibility. Pairing of the CCR5-D32 allele (HHG2) with HHC was associated with a reduced risk of transmission (p=0.03) whereas the haplotype pair HHE/HHG2 was associated with a nearly 4-fold higher likelihood of acquiring HIV-1 (p=0.04), highlighting the importance of CCR5 allele-allele interactions. A subset of the haplotype pairs associated with altered rates of transmissin and course of disease in children was similar to those that influenced disease progression in HIV infected adults. We also observed that if HHE was paired with HHF2 (CCR2-64I), a haplotype associated with delayed progression to AIDS (p=0.02), the disease accelerating effects of the HHE were negated. Among the HHF2 haplotype pairs, HHC/HHF2 was associated with the maximum disease retarding effects (p=0.01).Our findings demonstrate that genetic variation in CCR5 is an important determinant of susceptibility for HIV-1 transmission and clinical outcome in perinatally-infected children.

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