Associations of Chemokine Receptor Polymorphisms With HIV-1 Mother-to-Child Transmission in Sub-Saharan Africa: Possible Modulation of Genetic Effects by Antiretrovirals

Kumud Singh; Michael Hughes; Jie Chen; Kelesitse Phiri; Christine Rousseau; Louise Kuhn; Anna Coutsoudis; J Jackson; Laura Guay; Philippa Musoke; Francis Mmiro; Richard Semba; Stephen Spector

doi:10.1097/QAI.0b013e318186eaa4

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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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Associations of Chemokine Receptor Polymorphisms With HIV-1 Mother-to-Child Transmission in Sub-Saharan Africa: Possible Modulation of Genetic Effects by Antiretrovirals

Kumud Singh, Michael Hughes, Jie Chen, Kelesitse Phiri, Christine Rousseau, Louise Kuhn, Anna Coutsoudis, J Jackson, Laura Guay, Philippa Musoke, …

Journal of acquired immune deficiency syndromes (1999), Vol.49(3), pp.259-265

11/2008

DOI: 10.1097/QAI.0b013e318186eaa4

PMCID: PMC2748918

PMID: 18845960

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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 59029A allele vs. G/G [odds ratio (OR)1.61, 95% confidence interval (CI)1.04 to 2.48; P = 0.032] and 59356T allele vs. C/C (OR0.63, 95% CI0.41 to 0.96; P = 0.033) and CCR2-180G allele vs. A/A (OR3.32, 95% CI1.13 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.

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Title: Subtitle: Associations of Chemokine Receptor Polymorphisms With HIV-1 Mother-to-Child Transmission in Sub-Saharan Africa: Possible Modulation of Genetic Effects by Antiretrovirals
Creators: Kumud Singh - From the Department of Pediatrics, University of California San Diego, La Jolla, CA; †Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; ‡Department of Microbiology, University of Washington, Seattle, WA; §Department of Epidemiology, Columbia University, New York, NY; ‖Department of Pediatrics and Child Health, University of Natal, Durban, South Africa; ¶Department of Ophthalmology, Johns Hopkins University, Baltimore, MD; and #Departments of Pediatrics, and Obstetrics and Gynaecology, Makerere University, Kampala, Uganda
Michael Hughes
Jie Chen
Kelesitse Phiri
Christine Rousseau
Louise Kuhn
Anna Coutsoudis
J Jackson
Laura Guay
Philippa Musoke
Francis Mmiro
Richard Semba
Stephen Spector
Resource Type: Journal article
Publication Details: Journal of acquired immune deficiency syndromes (1999), Vol.49(3), pp.259-265
DOI: 10.1097/QAI.0b013e318186eaa4
PMID: 18845960
PMCID: PMC2748918
NLM abbreviation: J Acquir Immune Defic Syndr
ISSN: 1525-4135
eISSN: 1944-7884
Publisher: Lippincott Williams & Wilkins, Inc
Language: English
Date published: 11/2008
Academic Unit: Pathology; VPMA - Administration
Record Identifier: 9984047677702771

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