[59] MATERNAL VIRAL LOAD AND CCR5 CO-RECEPTOR UTILIZATION: CRITICAL DETERMINANTS IN MOTHER-TO-CHILD HIV-1 TRANSMISSION

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] MATERNAL VIRAL LOAD AND CCR5 CO-RECEPTOR UTILIZATION: CRITICAL DETERMINANTS IN MOTHER-TO-CHILD HIV-1 TRANSMISSION

[AUTHOR(S):] A Gormley¹, B Weiser¹, H Burger¹, C Kitchen², A Uppal¹, R Moore¹, C Brunner¹ and S Philpott¹
¹ New York State Department of Health, Albany, NY, USA; and ² University of California, Los Angeles, CA, USA

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 59
Antiviral Therapy 2003; 8(Suppl. 1):S198

[ABSTRACT:] Mother-to-child transmission of HIV-1 is a major route of infection worldwide, with rates of transmission in many developing countries ranging from 10-40%. Multiple factors play a role in vertical transmission, with maternal HIV-1 RNA load being a major determinant. In our 1995 study, statistical analyses identified plasma HIV-1 RNA load as a major factor in spread from mother to child; 8 of 10 women with the highest HIV-1 RNA levels transmitted, although none of the 20 women with lower levels did (P=0.002). Because HIV-1 strains that are transmitted in vivo generally use CCR5 as a coreceptor (R5 strains), we postulated that maternal HIV-1 phenotype in conjunction with viral load may influence transmission. We examined HIV-1 coreceptor usage and phenotype in the same 30 women studied previously, as well as several other virologic and immunogenetic characteristics. Significant differences were found between transmitting and non-transmitting mothers, not only with respect to total but also to R5-specific viral loads (P=0.0058 and 0.0054, respectively). Logistic regression analysis indicated that among the variables examined, total and R5 viral loads were the only significant predictors of transmission. Although total viral load correctly predicted transmission in 94.3% of cases (OR=45.15, 95% CI=3.144-649.0), R5 viral load correctly predicted 98% (OR=496.77, 95% CI=3.044-999.0). One non-transmitting mother, whose total viral load exceeded one million copies, had an R5 load of only ∼100,000. Our results suggest that CCR5 plays an essential role in vertical transmission. Blockade of this receptor may provide an additional strategy to prevent motherto- child transmission.

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