The effect of RANTES chemokine genetic variants on early HIV-1 plasma RNA among African American injection drug users.
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 log10 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.
Duggal
Priya
P
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Winkler
Cheryl A
CA
An
Ping
P
Yu
Xiao-Fang
XF
Farzadegan
Homayoon
H
O'Brien
Stephen J
SJ
Beaty
Terri H
TH
Vlahov
David
D
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000517:prevention & control*; D044383:Black People; D018946:Chemokine CCL5 / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D005786:Gene Expression Regulation; D014644:Genetic Variation; D005838:Genotype; D006679:HIV Seropositivity / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D011401:Promoter Regions, Genetic; D012367:RNA, Viral / Q000097:blood*; D015819:Substance Abuse, Intravenous / Q000097:blood / Q000235:genetics* / Q000821:virology; D019966:Substance-Related Disorders / Q000097:blood / Q000235:genetics* / Q000821:virology; D014481:United States; D019562:Viral Load; D001741:Black or African American
D018946:Chemokine CCL5; D012367:RNA, Viral