European mitochondrial DNA haplogroups and metabolic changes during antiretroviral therapy in AIDS Clinical Trials Group Study A5142.
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.
Hulgan
Todd
T
Vanderbilt University, Nashville, Tennessee, USA. todd.hulgan@vanderbilt.edu
Haubrich
Richard
R
Riddler
Sharon A
SA
Tebas
Pablo
P
Ritchie
Marylyn D
MD
McComsey
Grace A
GA
Haas
David W
DW
Canter
Jeffrey A
JA
D015502:Absorptiometry, Photon; D000293:Adolescent; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D017326:Clinical Trials, Phase III as Topic; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA; D055815:Young Adult
D004272:DNA, Mitochondrial; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors