title: 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.
authors.forename: Z
authors.initials: Z
authors.lastname: Dai
authors.forename: W
authors.initials: W
authors.lastname: Cai
authors.forename: F
authors.initials: F
authors.lastname: Hu
authors.forename: Y
authors.initials: Y
authors.lastname: Lan
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Chung
authors.forename: B
authors.initials: B
authors.lastname: Caughey
authors.affiliation: Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA. kang.zhang@gmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Tang
mesh_terms: D000328:Adult; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003521:Cyclopropanes; D004272:DNA, Mitochondrial / Q000097:blood*; D004338:Drug Combinations; D005260:Female; D006678:HIV / Q000187:drug effects / Q000502:physiology; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects; D008060:Lipodystrophy / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D061466:Lopinavir / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D019888:Nelfinavir / Q000008:administration & dosage / Q000009:adverse effects; D011237:Predictive Value of Tests; D012372:ROC Curve; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D015415:Biomarkers; D003521:Cyclopropanes; D004272:DNA, Mitochondrial; D004338:Drug Combinations; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D018119:Stavudine; D019888:Nelfinavir; C098320:efavirenz; D019438:Ritonavir