Mitochondrial RNA and DNA alterations in HIV lipoatrophy are linked to antiretroviral therapy and not to HIV infection.
BACKGROUND
The aim of this study was to assess the effect of antiretroviral therapy (ART) versus HIV on mitochondria in fat.


METHODS
Subcutaneous fat was collected from 45 HIV-infected patients on ART with lipoatrophy, 11 HIV-infected ART-naive patients and nine healthy controls. Three mitochondrial transcripts: NADH dehydrogenase subunit 1 (ND1), cytochrome B (CYTB) and NADH dehydrogenase subunit 6 (ND6) genes were quantitated using TaqMan probes and normalized to nuclear-encoded ribosomal L13.


RESULTS
ND1/L13 and CYTB/L13 were lower in HIV-positive patients on ART with lipoatrophy versus ART-naive patients (3.4 versus 7.2 [P=0.017] and 2.5 versus 4.6 [P=0.006], respectively). No difference was found between ART-naive patients and controls (P>0.70). ND6/L13 was similar between all groups. Dual-energy X-ray absorptiometry-measured limb fat and mitochondrial DNA in fat were also lower in HIV-positive patients on ART with lipoatrophy versus HIV-infected, ART-naive patients (4,382 versus 7,662 g [P=0.02] and 726 versus 1,372 copies/cell [P=0.03], respectively), but no difference was found between ART-naive and controls. In a multiple regression analysis, limb fat correlated with all three mitochrondrial RNA, whereas mitochondrial DNA did not correlate with mitochondrial RNA or limb fat.


CONCLUSIONS
In contrast to ART-naive patients, HIV-positive patients on ART with lipoatrophy had significant depletion in mitochondrial DNA in fat and mitochondrial RNAs. This suggests that mitochondrial toxicity in lipoatrophy could be driven by ART and not by HIV itself. In addition, mitochondrial RNA abnormalities, and not mitochondrial DNA depletion, could be a key driving force behind lipoatrophy.
McComsey
Grace A
GA
Case Western Reserve University, Cleveland, OH, USA. grace.mccomsey@case.edu
Libutti
Daniel E
DE
O'Riordan
MaryAnn
M
Shelton
Jessica M
JM
Storer
Norma
N
Ganz
Jason
J
Jasper
John
J
Harrill
Danielle
D
Gerschenson
Mariana
M
D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D004272:DNA, Mitochondrial / Q000032:analysis / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced* / Q000473:pathology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000032:analysis / Q000187:drug effects*; D000077278:RNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D000077278:RNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors; D012313:RNA
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