| European mitochondrial DNA haplogroups and metabolic changes during antiretroviral therapy in AIDS Clinical Trials Group Study A5142. | |
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MedLine Citation:
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PMID: 20871389 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Mitochondrial DNA (mtDNA) influences metabolic diseases and perhaps antiretroviral therapy (ART) complications. We explored associations between European mtDNA haplogroups and metabolic changes among A5142 participants. METHODS: Seven hundred and fifty-seven ART-naive patients were randomized to one of three class-sparing ART regimens including efavirenz and/or lopinavir/ritonavir with or without nucleoside reverse transcriptase inhibitors (NRTIs). Nonrandomized NRTIs included stavudine, tenofovir, or zidovudine, each with lamivudine. Fasting lipid profiles and whole-body dual-energy X-ray absorptiometry (DEXA) were performed. Nine European mtDNA haplogroups were determined for 231 self-identified non-Hispanic white individuals. Metabolic changes from baseline to 96 weeks were analyzed by haplogroup. RESULTS: Median age was 39 years, 9% were women, and 37, 32, and 30 were randomized to NRTI-containing regimens with either efavirenz or lopinavir/ritonavir, and an NRTI-sparing regimen, respectively. Among NRTI-containing regimens, 51% included zidovudine, 28% tenofovir, and 21% stavudine. Compared with other haplogroups, mtDNA haplogroup I (N = 10) had higher baseline non-HDL cholesterol [160 mg/dl (interquartile range 137-171) vs. 120 mg/dl (104-136); P = 0.005], a decrease in non-HDL cholesterol over 96 weeks [-14% (-20 to 6) vs. +25% (8 to 51); P < 0.001], tended to have more baseline extremity fat, and had more extremity fat loss by DEXA [-13% (-13 to 12) vs. +9% (-13 to 26); P = 0.08] and lipoatrophy (50 vs. 20%; P = 0.04). Haplogroup W (N = 5; all randomized to NRTI-sparing regimens) had the greatest increase in extremity fat [+35.5% (26.8 to 54.9); P = 0.02]. CONCLUSIONS: Lipids and extremity fat were associated with European mtDNA haplogroups in this HIV-infected population. These preliminary results suggest that mitochondrial genomics may influence metabolic parameters before and during ART. |
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Authors:
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Todd Hulgan; Richard Haubrich; Sharon A Riddler; Pablo Tebas; Marylyn D Ritchie; Grace A McComsey; David W Haas; Jeffrey A Canter |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: AIDS (London, England) Volume: 25 ISSN: 1473-5571 ISO Abbreviation: AIDS Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-01 Completed Date: 2011-03-25 Revised Date: 2012-01-04 |
Medline Journal Info:
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Nlm Unique ID: 8710219 Medline TA: AIDS Country: England |
Other Details:
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Languages: eng Pagination: 37-47 Citation Subset: IM; X |
Affiliation:
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Vanderbilt University, Nashville, Tennessee, USA. todd.hulgan@vanderbilt.edu |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00050895 |
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| MeSH Terms | |
Descriptor/Qualifier:
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Absorptiometry, Photon Adolescent Adult Aged Antiretroviral Therapy, Highly Active* Clinical Trials, Phase III as Topic DNA, Mitochondrial* / genetics Female HIV Infections / drug therapy*, genetics, metabolism HIV Protease Inhibitors / therapeutic use* HIV-1 / drug effects*, genetics HIV-Associated Lipodystrophy Syndrome / drug therapy*, genetics, metabolism Haplotypes / genetics Humans Male Middle Aged Retrospective Studies Reverse Transcriptase Inhibitors / therapeutic use* Sequence Analysis, DNA Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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AI 060354/AI/NIAID NIH HHS; AI 064086/AI/NIAID NIH HHS; AI 068634/AI/NIAID NIH HHS; AI 068636/AI/NIAID NIH HHS; AI 069411/AI/NIAID NIH HHS; AI 069418/AI/NIAID NIH HHS; AI 069419/AI/NIAID NIH HHS; AI 069423/AI/NIAID NIH HHS; AI 069424/AI/NIAID NIH HHS; AI 069432/AI/NIAID NIH HHS; AI 069434/AI/NIAID NIH HHS; AI 069439/AI/NIAID NIH HHS; AI 069447/AI/NIAID NIH HHS; AI 069450/AI/NIAID NIH HHS; AI 069452/AI/NIAID NIH HHS; AI 069465/AI/NIAID NIH HHS; AI 069470/AI/NIAID NIH HHS; AI 069471/AI/NIAID NIH HHS; AI 069472/AI/NIAID NIH HHS; AI 069474/AI/NIAID NIH HHS; AI 069477/AI/NIAID NIH HHS; AI 069484/AI/NIAID NIH HHS; AI 069494/AI/NIAID NIH HHS; AI 069495/AI/NIAID NIH HHS; AI 069501/AI/NIAID NIH HHS; AI 069502/AI/NIAID NIH HHS; AI 069513/AI/NIAID NIH HHS; AI 069532/AI/NIAID NIH HHS; AI 069556/AI/NIAID NIH HHS; AI 25859/AI/NIAID NIH HHS; AI 27661/AI/NIAID NIH HHS; AI 27673/AI/NIAID NIH HHS; AI 32782/AI/NIAID NIH HHS; AI 32783/AI/NIAID NIH HHS; AI 34853/AI/NIAID NIH HHS; AI 36214/AI/NIAID NIH HHS; AI 38858/AI/NIAID NIH HHS; AI 45008/AI/NIAID NIH HHS; AI 46370/AI/NIAID NIH HHS; AI 46376/AI/NIAID NIH HHS; AI 46381/AI/NIAID NIH HHS; AI 50410/AI/NIAID NIH HHS; AI 60484/AI/NIAID NIH HHS; AI 64086/AI/NIAID NIH HHS; AI 69432/AI/NIAID NIH HHS; DA 12121/DA/NIDA NIH HHS; K24 AI064086-01A1/AI/NIAID NIH HHS; K24 AI064086-06/AI/NIAID NIH HHS; K24 AI064086-07/AI/NIAID NIH HHS; P30 AI036214-10/AI/NIAID NIH HHS; R01 AI060484-01A2/AI/NIAID NIH HHS; RR 00032/RR/NCRR NIH HHS; RR 00039/RR/NCRR NIH HHS; RR 00044/RR/NCRR NIH HHS; RR 00046/RR/NCRR NIH HHS; RR 00047/RR/NCRR NIH HHS; RR 00051/RR/NCRR NIH HHS; RR 00052/RR/NCRR NIH HHS; RR 00075/RR/NCRR NIH HHS; RR 00096/RR/NCRR NIH HHS; RR 02635/RR/NCRR NIH HHS; RR024975/RR/NCRR NIH HHS; U01 AI068636-01/AI/NIAID NIH HHS; U01 AI069432-01/AI/NIAID NIH HHS; UL1 RR024975-01/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA, Mitochondrial; 0/HIV Protease Inhibitors; 0/Reverse Transcriptase Inhibitors |
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