title: Decreased mitochondrial DNA content in subcutaneous fat from HIV-infected women taking antiretroviral therapy as measured at delivery.
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.
authors.affiliation: Department of Biomedical Sciences, Section of General Pathology, University of Modena and Reggio Emilia, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Nasi
authors.forename: Marcello
authors.initials: M
authors.lastname: Pinti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Chiesa
authors.forename: Simona
authors.initials: S
authors.lastname: Fiore
authors.forename: Serena
authors.initials: S
authors.lastname: Manzini
authors.forename: Cinzia
authors.initials: C
authors.lastname: Del Giovane
authors.forename: Roberto
authors.initials: R
authors.lastname: D'Amico
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Palai
authors.forename: Carlo
authors.initials: C
authors.lastname: Campatelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Sabbatini
authors.forename: Marianna
authors.initials: M
authors.lastname: Roccio
authors.forename: Cecilia
authors.initials: C
authors.lastname: Tibaldi
authors.forename: Giulia
authors.initials: G
authors.lastname: Masuelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.forename: Enrico
authors.initials: E
authors.lastname: Ferrazzi
authors.forename: Antonella
authors.initials: A
authors.lastname: d'Arminio Monforte
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008076:Cholesterol, HDL / Q000097:blood; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000032:analysis* / Q000187:drug effects; D036861:Delivery, Obstetric; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D006679:HIV Seropositivity / Q000188:drug therapy / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D050151:Subcutaneous Fat / Q000737:chemistry* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D008076:Cholesterol, HDL; D004272:DNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors; D014280:Triglycerides