Highly active antiretroviral treatment (HAART) interruption leads to an increase in mitochondrial DNA content in HIV-infected children

  • C Morén
  • G Garrabou
  • N Rovira
  • A Noguera
  • M Nicolàs
  • F Cardellach
  • Ò Miró
  • C Fortuny
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Keywords

Nucleoside Analogue Transcriptase Inhibitor Mitochondrial Impairment 18SrRNA Gene Nucleoside Analogue Reverse Transcriptase Inhibitor 

Purpose of the study

HIV infection itself and antiretroviral treatment, especially nucleoside analogue reverse transcriptase inhibitors (NRTIs), cause mitochondrial impairment in HIV-infected patients, due to the inhibition of ã-polymerase, the only enzyme responsible for mitochondrial DNA (mtDNA) replication. We investigated whether there are changes in mtDNA content after 1 year of treatment interruption in children.

Methods

Mitochondrial DNA (mtDNA) was assessed by Real-Time Polymerase Chain Reaction (RT-PCR) in peripheral blood mononuclear cells (PBMCs) of 13 perinatally-HIV-infected pediatric patients, who underwent planned treatment interruption (PTI). MtDNA was measured at the time of PTI and 12 months later. A sequence of a highly conserved mtND2 gene and a fragment of the nuclear-coded housekeeping 18SrRNA gene were amplified separately. Changes in mtDNA amount were expressed as the ratio of ND2 mtDNA with respect to 18SrRNAnDNA.

Summary of results

MtDNA content significantly increased from 0.89 ± 0.173 to 1.48 ± 0.3429 (66%, p < 0.05) after 12-month treatment interruption.

Conclusion

MtDNA content restoration was found in a group of perinatally HIV-infected pediatric patients after 12 months of HAART interruption. Our results suggest that mitochondrial damage is rather due to the use of nucleoside analogues than to HIV infection itself. In this setting, it is important to investigate new therapeutic treatment-sparing strategies in HIV-infected pediatric patients.

Notes

Acknowledgements

Supported by Fundació la Marató de TV3 (020210 and 020631), FIPSE 36612/06, FIS 40381/04 and 41239/04, Suports a Grups de Recerca de la Generalitat de Catalunya (2005/SGR/0300) and CIBER de Enfermedades Raras (initiative of the ISCIII).

Copyright information

© Morén et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

Authors and Affiliations

  • C Morén
    • 1
  • G Garrabou
    • 1
  • N Rovira
    • 2
  • A Noguera
    • 2
  • M Nicolàs
    • 1
  • F Cardellach
    • 1
  • Ò Miró
    • 1
  • C Fortuny
    • 2
  1. 1.Mitochondrial Research Laboratory-IDIBAPS-Hospital Clínic of Barcelona and CIBERERBarcelonaSpain
  2. 2.Hospital Sant Joan de DéuBarcelonaSpain

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