Mitochondrial DNA depletion in adipose tissue of HIV-infected patients with peripheral lipoatrophy

• Published in: Journal of clinical virology 2005-05, Vol.33 (1), p.60-64
• Main Authors: Buffet, Marc, Schwarzinger, Michaël, Amellal, Bahia, Gourlain, Karine, Bui, Patrick, Prévot, Marianne, Deleuze, Jean, Morini, Jean-Pierre, Gorin, Isabelle, Calvez, Vincent, Dupin, Nicolas
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adipose Tissue - pathology; Adolescent; Adult; Aged; Anti-HIV Agents - adverse effects; Antiretroviral therapy; Biological and medical sciences; Didanosine - adverse effects; DNA, Mitochondrial - drug effects; DNA, Mitochondrial - metabolism; Female; Fundamental and applied biological sciences. Psychology; HIV; HIV Infections - drug therapy; HIV Infections - virology; HIV-1; HIV-Associated Lipodystrophy Syndrome - chemically induced; Human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Mitochondrial DNA; Peripheral lipoatrophy; Reverse Transcriptase Inhibitors - adverse effects; Stavudine - adverse effects; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology
• ISSN: 1386-6532; 1873-5967
• DOI: 10.1016/j.jcv.2004.09.027

NRTI-induced host toxicity is proposed to involve cellular mitochondrial DNA (mtDNA) depletion. Determinants of cellular mtDNA copy number from HIV-infected patients receiving HAART and HIV-seronegative controls were investigated from subcutaneous fat samples, and relation with antiretroviral regimen was studied. HIV-infected patients receiving HAART ( n = 50), HIV-infected patients not currently under HAART regimen ( n = 2) and HIV-seronegative controls ( n = 9) of similar age and BMI were enrolled prospectively when undergoing Coleman's lipostructure for correction of facial lipoatrophy or plastic surgery, respectively. After centrifugation, abdominal fat tissue was collected and stored at −80 °C. MtDNA analysis was blindly performed after a total DNA extraction from adipose tissue, followed by a real-time PCR quantification. The log of mtDNA copies/cell in adipose tissue [log(DNA)] was compared between groups by means of analysis of variance. The log(DNA) in adipose tissue of HIV-infected patients was significantly lower than in the HIV-seronegative control group ( P < 0.0001). In HIV-infected patients, log(DNA) was significantly reduced in the 50 NRTI-treated patients ( P < 0.01), but not when considering mtDNA level according to the use of PI or NNRTI in current HAART regimen. In NRTI-treated patients, only stavudine ( n = 20) and didanosine ( n = 14) were significantly and independently associated with reduced mtDNA level ( P < 0.0001 and