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J Acquir Immune Defic Syndr. 2008 Nov 1;49(3):259-65. doi: 10.1097/QAI.0b013e318186eaa4.

Associations of chemokine receptor polymorphisms With HIV-1 mother-to-child transmission in sub-Saharan Africa: possible modulation of genetic effects by antiretrovirals.

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  • 1Department of Pediatrics, University of California San Diego, La Jolla, CA 92093-0672, USA.

Abstract

BACKGROUND:

HIV-1 mother-to-child transmission (MTCT) remains an important route of infection in sub-Saharan Africa.

METHODS:

Genetic variants in CCR5 promoter, CCR2, CX3CR1, and Stromal cell-derived factor-1 (SDF-1) genes were determined in 980 infants from sub-Saharan Africa using real-time polymerase chain reaction to determine association with MTCT.

RESULTS:

In antiretroviral-naive mother-infant pairs (n = 637), CCR5 promoter polymorphisms at positions 59029: A allele vs. G/G [odds ratio (OR): 1.61, 95% confidence interval (CI): 1.04 to 2.48; P = 0.032] and 59356: T allele vs. C/C (OR: 0.63, 95% CI: 0.41 to 0.96; P = 0.033) and CCR2-180: G allele vs. A/A (OR: 3.32, 95% CI: 1.13 to 9.73; P = 0.029) were associated with risk of MTCT. Treatment of HIV-1-infected mothers and infants with single-dose nevirapine or perinatal zidovudine altered but did not eliminate the association of genetic variants with MTCT.

CONCLUSIONS:

CCR5 promoter, CCR2, and CX3CR1 polymorphisms were associated with risk of MTCT likely through their role as an HIV-1 coreceptor or by modulating the early immune response. Host genetics may continue to alter MTCT when short-course interventions that only partially suppress virus are used. These findings will need to be confirmed in validation cohorts with a large number of infected infants.

PMID:
18845960
PMCID:
PMC2748918
DOI:
10.1097/QAI.0b013e318186eaa4
[PubMed - indexed for MEDLINE]
Free PMC Article
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