The effect of RANTES chemokine genetic variants on early HIV-1 plasma RNA among African American injection drug users

Priya Duggal, Cheryl A. Winkler, Ping An, Xiao Fang Yu, Homayoon Farzadegan, Stephen J. O'Brien, Terri H. Beaty, David Vlahov

Research output: Contribution to journalArticle

Abstract

HIV-1 plasma RNA is a prognostic indicator of HIV-1, and increased levels of HIV-1 plasma RNA are associated with rapid progression to AIDS. Because chemokines and chemokine receptors are involved in the binding and entry of HIV-1, possible effects of host genetics on viral RNA levels should be visible in early infection. HIV-1 plasma RNA was measured within 2 years of seroconversion in 198 seroincident injection drug users followed in the AIDS Link to Intravenous Experience cohort. Genetic variants were identified in the chemokine receptors (CCR2, CCR5, and CCR5 promoter) and the chemokine RANTES using TaqMan and restriction fragment length polymorphism assays. Linear regression of RANTES haplotypes on early HIV-1 plasma RNA identified individuals homozygous for the RANTES R1 haplotype as having a lower viral load by almost one-half logic unit compared with those bearing non-RANTES R1 haplotypes (-0.43, 95% confidence interval: -0.74, -0.12). Genetic variants in RANTES may downregulate RANTES gene expression and increase early HIV-1 plasma RNA. Because RANTES is a critical chemokine and competitively inhibits HIV-1 by binding to its receptor CCR5, treatment to enhance RANTES expression may assist in delaying the progression of AIDS by decreasing the initial viral load.

Original languageEnglish (US)
Pages (from-to)584-589
Number of pages6
JournalJournal of acquired immune deficiency syndromes
Volume38
Issue number5
DOIs
StatePublished - Apr 15 2005

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Keywords

  • Chemokines
  • HIV
  • HIV-1 plasma RNA
  • RANTES

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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