title: Prospective evaluation of blood concentration of mitochondrial DNA as a marker of toxicity in 157 consecutively recruited untreated or HAART-treated HIV-positive patients.
abstract: Highly active antiretroviral therapy (HAART) can cause mitochondrial toxicity. The concentration of mitochondrial DNA (mtDNA) in peripheral blood cells has been reported to be a marker of this toxicity. However, these observations are controversial and were drawn from small series. Thus, we analysed the value of blood mtDNA as a marker of mitochondrial toxicity in a large cohort of human immunodeficiency virus (HIV)-infected out-patients during routine clinical evaluations. Real-time quantitative PCR was used to determine the mtDNA to nuclear DNA (nDNA) ratio in peripheral blood mononuclear cells from 157 consecutive HIV-1-infected patients (13 naive, 144 receiving HAART) and 30 HIV-1-uninfected patients. The mtDNA to nDNA ratio was significantly lower in both groups of HIV-infected patients than in the control group. No significant difference was observed between treated and naive HIV-infected patients. Lactataemia was significantly lower in controls than in the group of HIV-treated patients. None of the treated patients had lactataemia >5 mmol/l or bicarbonates <20 mmol/l. Triglyceride levels were significantly higher in the HAART-treated patients than in the nontreated patients. Clinical symptoms of lipodystrophy were observed in 62 HAART-treated patients. These symptoms were not associated with an abnormal mtDNA to nDNA ratio or plasma triglyceride concentration. The mtDNA to nDNA ratio was lower in DDI/D4T-treated patients than in AZT/3TC-treated patients. In conclusion, there are no obvious links between the mtDNA to nDNA ratio in peripheral mononuclear cells and any clinical symptoms or lactate level. Thus, the mtDNA to nDNA ratio in leukocytes does not seem to be an accurate marker of mild and/or long-term mitochondrial toxicity.
authors.affiliation: Service de Biochimie et de Biologie Moléculaire-INSERM 602, Hôpital Paul Brousse, 12 avenue Paul Vaillant-Couturier, 94800 Villejuif, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Chiappini
authors.forename: Elina
authors.initials: E
authors.lastname: Teicher
authors.forename: Raphaël
authors.initials: R
authors.lastname: Saffroy
authors.forename: Patrick
authors.initials: P
authors.lastname: Pham
authors.forename: Bruno
authors.initials: B
authors.lastname: Falissard
authors.forename: Alain
authors.initials: A
authors.lastname: Barrier
authors.forename: Stephan
authors.initials: S
authors.lastname: Chevalier
authors.forename: Brigitte
authors.initials: B
authors.lastname: Debuire
authors.forename: Daniel
authors.initials: D
authors.lastname: Vittecoq
authors.forename: Antoinette
authors.initials: A
authors.lastname: Lemoine
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D004272:DNA, Mitochondrial / Q000097:blood*; D005260:Female; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000209:etiology; D006801:Humans; D007773:Lactates / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects*; D011446:Prospective Studies
chemical_list: D004272:DNA, Mitochondrial; D007773:Lactates; D008055:Lipids