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Plasma Mitochondrial DNA Levels as a Biomarker of Lipodystrophy Among HIV-infected Patients Treated with Highly Active Antiretroviral Therapy (HAART).

Abstract
Lipodystrophy is a common complication in HIV-infected patients taking highly active antiretroviral therapy. Its early diagnosis is crucial for timely modification of antiretroviral therapy. We hypothesize that mitochondrial DNA in plasma may be a potential marker of LD in HIV-infected individuals. In this study, we compared plasma mitochondrial DNA levels in HIV-infected individuals and non-HIV-infected individuals to investigate its potential diagnostic value. Total plasma DNA was extracted from 67 HIV-infected patients at baseline and 12, 24 and 30 months after initiating antiretroviral therapy. Real-time quantitative PCR was used to determine the mitochondrial DNA levels in plasma. Lipodystrophy was defined by the physician-assessed presence of lipoatrophy or lipohypertrophy in one or more body regions. The mitochondrial DNA levels in plasma were significantly higher at baseline in HIV-infected individuals than in non-HIV-infected individuals (p<0.05). At month 30, 33 out of 67 patients (49.2%) showed at least one sign of lipodystrophy. The mean plasma mitochondrial DNA levels in lipodystrophy patients were significantly higher compared to those without lipodystrophy at month 24 (p<0.001). The receiver operating curve analysis demonstrated that using plasma mitochondrial DNA level (with cut-off value <5.09 log10 copies/ml) as a molecular marker allowed identification of patients with lipodystrophy with a sensitivity of 64.2% and a specificity of 73.0%. Our data suggest that mitochondrial DNA levels may help to guide therapy selection with regards to HIV lipodystrophy risk.
AuthorsZ Dai, W Cai, F Hu, Y Lan, L Li, C Chung, B Caughey, K Zhang, X Tang
JournalCurrent molecular medicine (Curr Mol Med) Vol. 15 Issue 10 Pg. 975-9 ( 2015) ISSN: 1875-5666 [Electronic] Netherlands
PMID26592244 (Publication Type: Journal Article)
Chemical References
  • Alkynes
  • Benzoxazines
  • Biomarkers
  • Cyclopropanes
  • DNA, Mitochondrial
  • Drug Combinations
  • lopinavir-ritonavir drug combination
  • Lopinavir
  • Lamivudine
  • Zidovudine
  • Stavudine
  • Nelfinavir
  • efavirenz
  • Ritonavir
Topics
  • Adult
  • Alkynes
  • Antiretroviral Therapy, Highly Active (adverse effects)
  • Benzoxazines (administration & dosage, adverse effects)
  • Biomarkers (blood)
  • Case-Control Studies
  • Cyclopropanes
  • DNA, Mitochondrial (blood)
  • Drug Combinations
  • Female
  • HIV (drug effects, physiology)
  • HIV Infections (blood, drug therapy, pathology, virology)
  • Humans
  • Lamivudine (administration & dosage, adverse effects)
  • Lipodystrophy (blood, chemically induced, diagnosis, pathology)
  • Lopinavir (administration & dosage, adverse effects)
  • Male
  • Middle Aged
  • Mitochondria (metabolism, pathology)
  • Nelfinavir (administration & dosage, adverse effects)
  • Predictive Value of Tests
  • ROC Curve
  • Ritonavir (administration & dosage, adverse effects)
  • Stavudine (administration & dosage, adverse effects)
  • Zidovudine (administration & dosage, adverse effects)

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