Biology Faculty Articles
Title
Host Genetic Influences on Highly Active Antiretroviral Therapy Efficacy and AIDS-Free Survival
Document Type
Article
Publication Date
7-1-2008
Publication Title
Journal of Acquired Immune Deficiency Syndromes
Keywords
AIDS, AIDS restriction gene, Highly active antiretroviral therapy, Single-nucleotide polymorphism
ISSN
1525-4135
Volume
48
Issue/No.
3
First Page
263
Last Page
271
Abstract
We studied the influence of AIDS restriction genes (ARGs) CCR5-Δ32, CCR2-64I, SDF1-3′A, IL10-5′A, CX3CR1-V249I, CX3CR1-T280M, and MDR1-C3435T and haplotypes of the CCR5 P1 promoter and RANTES variants −403A, In1.1C, 3′222C, and −28G among HIV-1 infected patients on highly active antiretroviral therapy (HAART) in the Multicenter AIDS Cohort Study (MACS) and the Multicenter Hemophilia Cohort Study (MHCS). Our results indicate that several ARGs also influence therapy efficacy (ie, the success in viral suppression) and subsequent progression to AIDS while on HAART. CCR5-Δ32 decreased time to viral suppression (<200 HIV RNA copies/mL, relative hazard [RH] = 1.40; P = 0.008) and was protective against AIDS (RH = 0.11; P = <0.0001), whereas the CCR5 P1 haplotype was associated with delayed viral suppression (RNA <50 copies/mL, odds ratio [OR] = 0.65; P = 0.03) and accelerated time to AIDS (RH = 2.68; P = 0.02). SDF1-3′A reduced viral suppression (OR = 0.61; P = 0.02) and accelerated AIDS (RH = 3.18; P = 0.009). Accelerated AIDS progression was also observed with the RANTES haplotype carrying RANTES-IN1.1C and RANTES-3′222C (P = 0.005 to 0.007). In contrast, the RANTES haplotype H1, which lacks suspected deleterious single-nucleotide polymorphisms, was protective against AIDS. CX3CR1-V249I seemed to accelerate viral suppression (RNA <50 copies/mL, OR = 1.27; P = 0.01). ARG influence after HAART suggests residual HIV-1 replication, and spread continues even in patients successfully suppressing detectable viral RNA.
Additional Comments
National Cancer Institute contract #s: UO1-AI-35042, 5-MO1-RR-00722, UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041, and N01-CO-12400
NSUWorks Citation
Hendrickson, Sher L.; Lisa Jacobson; George W. Nelson; John Phair; J. A. Lautenberger; Randall C. Johnson; Lawrence Kingsley; Joseph Margolick; Roger Detels; James J. Goedert; and Stephen J. O'Brien. 2008. "Host Genetic Influences on Highly Active Antiretroviral Therapy Efficacy and AIDS-Free Survival." Journal of Acquired Immune Deficiency Syndromes 48, (3): 263-271. https://nsuworks.nova.edu/cnso_bio_facarticles/491
ORCID ID
0000-0001-7353-8301
ResearcherID
N-1726-2015
Comments
©2008 by Lippincott Williams & Wilkins