| Host genetic influences on highly active antiretroviral therapy efficacy and AIDS-free survival. | |
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MedLine Citation:
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PMID: 18391751 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We studied the influence of AIDS restriction genes (ARGs) CCR5-Delta32, 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-Delta32 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=or<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. |
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Authors:
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Sher L Hendrickson; Lisa P Jacobson; George W Nelson; John P Phair; James Lautenberger; Randall C Johnson; Lawrence Kingsley; Joseph B Margolick; Roger Detels; James J Goedert; Stephen J O'Brien |
Publication Detail:
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Type: Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural |
Journal Detail:
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Title: Journal of acquired immune deficiency syndromes (1999) Volume: 48 ISSN: 1525-4135 ISO Abbreviation: J. Acquir. Immune Defic. Syndr. Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-06-26 Completed Date: 2008-07-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100892005 Medline TA: J Acquir Immune Defic Syndr Country: United States |
Other Details:
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Languages: eng Pagination: 263-71 Citation Subset: IM; X |
Affiliation:
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Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD 21702-1201, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acquired Immunodeficiency Syndrome
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genetics* Antiretroviral Therapy, Highly Active* CD4 Lymphocyte Count* Chemokine CCL5 / genetics Cohort Studies Disease Progression European Continental Ancestry Group Genotype HIV-1 / drug effects* Humans Male P-Glycoprotein / genetics* Polymorphism, Single Nucleotide |
| Grant Support | |
ID/Acronym/Agency:
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5-M01-RR-00722/RR/NCRR NIH HHS; N01-CO-12400/CO/NCI NIH HHS; U01-AI-35039/AI/NIAID NIH HHS; U01-AI-35040/AI/NIAID NIH HHS; U01-AI-35041/AI/NIAID NIH HHS; U01-AI-35042/AI/NIAID NIH HHS; U01-AI-35043/AI/NIAID NIH HHS; U01-AI-37613/AI/NIAID NIH HHS; U01-AI-37984/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CCL5; 0/P-Glycoprotein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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