Depletion of mitochondrial DNA copies/cell in peripheral blood mononuclear cells in HIV‐1‐infected treatment‐naïve patients

Objectives Mitochondrial toxicity is believed to be the main reason for adverse effects related to nucleoside reverse transcriptase inhibitors (NRTIs). The aim of the present study was to compare mitochondrial toxicity in NRTI‐treated HIV‐positive patients, HIV‐positive treatment‐naïve patients and...

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Bibliographic Details
Published in:HIV medicine 2006-01, Vol.7 (1), p.53-58
Main Authors: Maagaard, A, Holberg‐Petersen, M, Kvittingen, EA, Sandvik, L, Bruun, JN
Format: Article
Language:English
Subjects:
Adult
Aged
Anti-HIV Agents - adverse effects
Biomarkers - blood
DNA polymerase γ
DNA, Mitochondrial - blood
DNA, Mitochondrial - drug effects
Drug Monitoring - methods
Female
HIV Infections - blood
HIV Infections - drug therapy
HIV-1 - isolation & purification
HIV‐1
Human immunodeficiency virus
Humans
lactate/pyruvate ratio
Lactic Acid - blood
Leukocytes, Mononuclear - chemistry
Male
Middle Aged
mitochondrial toxicity
Pyruvic Acid - blood
Reverse Transcriptase Inhibitors - adverse effects
Reverse Transcriptase Polymerase Chain Reaction
RNA, Viral - blood
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Summary:Objectives Mitochondrial toxicity is believed to be the main reason for adverse effects related to nucleoside reverse transcriptase inhibitors (NRTIs). The aim of the present study was to compare mitochondrial toxicity in NRTI‐treated HIV‐positive patients, HIV‐positive treatment‐naïve patients and HIV‐negative controls by comparing mitochondrial DNA (mtDNA) copies/cell in peripheral blood mononuclear cells (PBMCs) and lactate/pyruvate (L/P) ratios in the different groups. Methods We enrolled 60 participants in the study: 31 patients on combined antiretroviral therapy (CART), 14 HIV‐positive treatment‐naive patients and 15 HIV‐negative controls. mtDNA (copies/cell) in peripheral blood was analysed using quantitative real‐time polymerase chain reaction (PCR). Standard curves and serial dilutions of plasmid‐cloned mitochondrion and retinoblastoma (RB1) PCR products with known concentrations were generated to estimate the mtDNA and nuclear DNA (nDNA) copy numbers in each sample. The L/P ratio was enzymatically and spectrophotometrically analysed in samples from individuals in a fasted, non‐exercise state. Results The median mtDNA copy number was 63 copies/cell (interquartile range 33–94) in HIV‐positive patients and 153 (132–283) in HIV‐negative controls (P
ISSN:1464-2662
1468-1293
DOI:10.1111/j.1468-1293.2005.00336.x