European mitochondrial DNA haplogroups and metabolic changes during antiretroviral therapy in AIDS Clinical Trials Group Study A5142.

TitleEuropean mitochondrial DNA haplogroups and metabolic changes during antiretroviral therapy in AIDS Clinical Trials Group Study A5142.
Publication TypeJournal Article
Year of Publication2011
AuthorsHulgan T, Haubrich R, Riddler SA, Tebas P, Ritchie MD, McComsey GA, Haas DW, Canter JA
JournalAIDS
Volume25
Issue1
Pagination37-47
Date Published2011 Jan 2
ISSN1473-5571
KeywordsAbsorptiometry, Photon, Adolescent, Adult, Aged, Antiretroviral Therapy, Highly Active, Clinical Trials, Phase III as Topic, DNA, Mitochondrial, Female, Haplotypes, HIV Infections, HIV Protease Inhibitors, HIV-1, HIV-Associated Lipodystrophy Syndrome, Humans, Male, Middle Aged, Retrospective Studies, Reverse Transcriptase Inhibitors, Sequence Analysis, DNA, Young Adult
Abstract

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.

DOI10.1097/QAD.0b013e32833f9d02
Alternate JournalAIDS
PubMed ID20871389
PubMed Central IDPMC2995830
Grant ListAI 060354 / AI / NIAID NIH HHS / United States
AI 064086 / AI / NIAID NIH HHS / United States
AI 068634 / AI / NIAID NIH HHS / United States
AI 068636 / AI / NIAID NIH HHS / United States
AI 069411 / AI / NIAID NIH HHS / United States
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