Prospective evaluation of blood concentration of mitochondrial DNA as a marker of toxicity in 157 consecutively recruited untreated or HAART-treated HIV-positive patients
被引:46
作者:
Chiappini, F
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机构:Hop Paul Brousse, Serv Biochim & Biol Mol, INSERM 602, F-94800 Villejuif, France
Chiappini, F
Teicher, E
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机构:Hop Paul Brousse, Serv Biochim & Biol Mol, INSERM 602, F-94800 Villejuif, France
Teicher, E
Saffroy, R
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机构:Hop Paul Brousse, Serv Biochim & Biol Mol, INSERM 602, F-94800 Villejuif, France
Saffroy, R
Pham, P
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机构:Hop Paul Brousse, Serv Biochim & Biol Mol, INSERM 602, F-94800 Villejuif, France
Pham, P
Falissard, B
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机构:Hop Paul Brousse, Serv Biochim & Biol Mol, INSERM 602, F-94800 Villejuif, France
Falissard, B
Barrier, A
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机构:Hop Paul Brousse, Serv Biochim & Biol Mol, INSERM 602, F-94800 Villejuif, France
Barrier, A
Chevalier, S
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机构:Hop Paul Brousse, Serv Biochim & Biol Mol, INSERM 602, F-94800 Villejuif, France
Chevalier, S
Debuire, B
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机构:Hop Paul Brousse, Serv Biochim & Biol Mol, INSERM 602, F-94800 Villejuif, France
Debuire, B
Vittecoq, D
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机构:Hop Paul Brousse, Serv Biochim & Biol Mol, INSERM 602, F-94800 Villejuif, France
Vittecoq, D
Lemoine, A
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机构:Hop Paul Brousse, Serv Biochim & Biol Mol, INSERM 602, F-94800 Villejuif, France
Lemoine, A
机构:
[1] Hop Paul Brousse, Serv Biochim & Biol Mol, INSERM 602, F-94800 Villejuif, France
[2] Univ Paris 11, Fac Med, Hop Paul Brousse, Serv Sante Publ, Villejuif, France
[3] Univ Paris 11, Fac Med, Hop Paul Brousse, Serv Infectiol, Villejuif, France
[4] PFIZER, Ctr Rech, Amboise, France
[5] Hop St Antoine, INSERM 444, F-75571 Paris, France
HAART toxicity;
HIV infection;
lactataemia;
lipodystrophy;
mitochondrial DNA;
mitochondrial toxicity;
D O I:
10.1038/labinvest.3700113
中图分类号:
R-3 [医学研究方法];
R3 [基础医学];
学科分类号:
1001 ;
摘要:
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.
机构:
Hop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, FranceHop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, France
Brivet, FG
Nion, I
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机构:Hop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, France
Nion, I
Mégarbane, B
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机构:Hop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, France
Mégarbane, B
Slama, A
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机构:Hop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, France
Slama, A
Brivet, M
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机构:Hop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, France
Brivet, M
Rustin, P
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机构:Hop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, France
Rustin, P
Munnich, A
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机构:Hop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, France
机构:
St Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, AustraliaSt Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia
Carr, A
Miller, J
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机构:St Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia
Miller, J
Law, M
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机构:St Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia
Law, M
Cooper, DA
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机构:St Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia
机构:
Hop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, FranceHop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, France
Brivet, FG
Nion, I
论文数: 0引用数: 0
h-index: 0
机构:Hop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, France
Nion, I
Mégarbane, B
论文数: 0引用数: 0
h-index: 0
机构:Hop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, France
Mégarbane, B
Slama, A
论文数: 0引用数: 0
h-index: 0
机构:Hop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, France
Slama, A
Brivet, M
论文数: 0引用数: 0
h-index: 0
机构:Hop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, France
Brivet, M
Rustin, P
论文数: 0引用数: 0
h-index: 0
机构:Hop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, France
Rustin, P
Munnich, A
论文数: 0引用数: 0
h-index: 0
机构:Hop Antoine Beclere, Dept Emergency Med & Med Intens Care, Clamart, France
机构:
St Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, AustraliaSt Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia
Carr, A
Miller, J
论文数: 0引用数: 0
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机构:St Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia
Miller, J
Law, M
论文数: 0引用数: 0
h-index: 0
机构:St Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia
Law, M
Cooper, DA
论文数: 0引用数: 0
h-index: 0
机构:St Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia