Decreased mitochondrial DNA content in subcutaneous fat from HIV-infected women taking antiretroviral therapy as measured at delivery

Milena Nasi, Marcello Pinti, Elisabetta Chiesa, Simona Fiore, Serena Manzini, Cinzia Del Giovane, Roberto D'Amico, Nicoletta Palai, Carlo Campatelli, Francesca Sabbatini, Marianna Roccio, Cecilia Tibaldi, Giulia Masuelli, Cristina Mussini, Enrico Ferrazzi, Antonella D'Arminio Monforte, Andrea Cossarizza

Research output: Contribution to journalArticle

Abstract

Background: Increasing numbers of pregnant HIV-positive women are receiving combination antiretroviral regimens for preventing mother-to-child virus transmission or for treating the infection itself. Several studies have demonstrated that nucleoside reverse transcriptase inhibitors (NRTIs) induce mitochondrial toxicity by several mechanisms, including depletion of mitochondrial DNA (mtDNA). By the quantification of mtDNA levels, we studied mitochondrial toxicity in HIV-positive women at delivery and the possible correlations with antiretroviral regimens, viroimmunological and metabolic parameters. Methods: We analysed 68 HIV-positive women enrolled in the Italian Prospective Cohort Study on Efficacy and Toxicity of Antiretroviral in Pregnancy (TARGET Study); all were taking ≥1 NRTI. We quantified mtDNA copies per cell in subcutaneous fat samples collected during delivery. At the 3rd, 6th and 9th month of pregnancy, we collected data concerning CD4+ T-cell count, plasma HIV RNA, total and high-density lipoprotein (HDL) cholesterol, fasting plasma glucose and triglycerides. As a control, we analysed mtDNA levels in abdominal subcutaneous fat samples from 23 HIV-seronegative women at delivery. Results: mtDNA content was significantly lower in HIV-infected women when compared with HIV-negative controls. mtDNA content varied independently from viroimmunological, lipid and glucose parameters at the different months, with the exceptions of triglycerides at the 9th month and of HDL at the 6th month of pregnancy. Conclusions: In subcutaneous tissue from women taking NRTI-based antiretroviral regimens, we observed a significant decrease of mtDNA content, compared with uninfected women not on antiviral treatment. Moreover, a significant correlation was noted between mtDNA content and HDL cholesterol and triglycerides.

Original languageEnglish
Pages (from-to)365-372
Number of pages8
JournalAntiviral Therapy
Volume16
Issue number3
DOIs
Publication statusPublished - 2011

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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    Nasi, M., Pinti, M., Chiesa, E., Fiore, S., Manzini, S., Del Giovane, C., D'Amico, R., Palai, N., Campatelli, C., Sabbatini, F., Roccio, M., Tibaldi, C., Masuelli, G., Mussini, C., Ferrazzi, E., D'Arminio Monforte, A., & Cossarizza, A. (2011). Decreased mitochondrial DNA content in subcutaneous fat from HIV-infected women taking antiretroviral therapy as measured at delivery. Antiviral Therapy, 16(3), 365-372. https://doi.org/10.3851/IMP1764