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

Kumud K. Singh, Michael D. Hughes, Jie Chen, Kelesitse Phiri, Christine Rousseau, Louise Kuhn, Anna Coutsoudis, J. Brooks Jackson, Laura A. Guay, Philippa Musoke, Francis Mmiro, Richard D. Semba, Stephen A. Spector

Research output: Contribution to journalArticle

Abstract

HIV-1 mother-to-child transmission (MTCT) remains an important route of infection in sub-Saharan Africa. Genetic variants in CCR5 promoter, CCR2, CX 3CRX, 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. In antiretroviral-naive mother-infant pairs (n = 637), CCRS 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: Ta 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. CCR5 promoter, CCR2, and CX 3CR1 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 MTCTwhen 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.

Original languageEnglish (US)
Pages (from-to)259-265
Number of pages7
JournalJournal of acquired immune deficiency syndromes
Volume49
Issue number3
DOIs
StatePublished - Nov 2008

Keywords

  • Antiretrovirals
  • Chemokine/ chemokine receptor genotypes
  • HIV-1
  • Mother-to-child transmission

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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  • Cite this

    Singh, K. K., Hughes, M. D., Chen, J., Phiri, K., Rousseau, C., Kuhn, L., Coutsoudis, A., Jackson, J. B., Guay, L. A., Musoke, P., Mmiro, F., Semba, R. D., & Spector, S. A. (2008). Associations of chemokine receptor polymorphisms with HIV-1 mother-to-child transmission in sub-Saharan Africa: Possible modulation of genetic effects by antiretrovirals. Journal of acquired immune deficiency syndromes, 49(3), 259-265. https://doi.org/10.1097/QAI.0b013e318186eaa4