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

AIDS. 2011 Jan 2;25(1):37-47. doi: 10.1097/QAD.0b013e32833f9d02.

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.

Trial registration: ClinicalTrials.gov NCT00050895.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Absorptiometry, Photon
  • Adolescent
  • Adult
  • Aged
  • Antiretroviral Therapy, Highly Active*
  • Clinical Trials, Phase III as Topic
  • DNA, Mitochondrial* / genetics
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / metabolism
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-Associated Lipodystrophy Syndrome / drug therapy*
  • HIV-Associated Lipodystrophy Syndrome / genetics
  • HIV-Associated Lipodystrophy Syndrome / metabolism
  • Haplotypes / genetics
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Sequence Analysis, DNA
  • Young Adult

Substances

  • DNA, Mitochondrial
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors

Associated data

  • ClinicalTrials.gov/NCT00050895

Grant support