Journal article
Tissue-specific associations between mitochondrial DNA levels and current treatment status in HIV-Infected individuals
JAIDS Journal of Acquired Immune Deficiency Syndromes, Vol.42(4), pp.435-440
2006
Abstract
Background: Tissue mitochondrial DNA (mtDNA) levels have been proposed as a marker of nucleoside analouge reverse transcriptase inhibitor (NRTI) toxicity. However, clinical studies have yielded conflicting data regarding possible associations with mtDNA levels. This study examined mtDNA levels in matched samples of peripheral blood mononuclear cells (PBMCs) and subcutaneous fat from a large Australian cohort to examine treatment, clinical, and demographic associations with mtDNA depletion.
Methods: mtDNA was quantified by real-time polymerase chain reaction. Results were compared across patient treatment and demographic details using linear mixed models.
Results: One hundred sixty-three PBMCs and 161 fat samples were available from 61 individuals. Current NRTI exposure was the major determinant of mtDNA levels. Both ddI (didanosine) and d4T (stavudine) exposures were associated with mtDNA depletion in fat (P <= 0.0001 vs. those not on NRTIs). DdI exposure (P = 0.003), but not d4T exposure (P = 0.5), was associated with mtDNA depletion in PBMCs. No association between patient demographics or time on current therapy and mtDNA was observed.
Conclusions: Current NRTI exposure is the major determinant of tissue mtDNA, but the precise determinants are tissue specific. Both ddI and d4T exposure are associated with fat mtDNA depletion, whereas ddI exposure was the only observed association with mtDNA depletion in PBMCs.
Details
- Title
- Tissue-specific associations between mitochondrial DNA levels and current treatment status in HIV-Infected individuals
- Authors/Creators
- C.L. Cherry (Author/Creator) - The Alfred HospitalD. Nolan (Author/Creator) - Murdoch UniversityI.R. James (Author/Creator) - Murdoch UniversityE.J. McKinnon (Author/Creator) - Murdoch UniversityS.A. Mallal (Author/Creator) - Murdoch UniversityM.E. Gahan (Author/Creator) - Burnet InstituteL. Lal (Author/Creator) - Burnet InstituteJ.C. McArthur (Author/Creator) - Johns Hopkins UniversityS.L. Wesselingh (Author/Creator) - The Alfred Hospital
- Publication Details
- JAIDS Journal of Acquired Immune Deficiency Syndromes, Vol.42(4), pp.435-440
- Publisher
- Lippincott Williams & Wilkins
- Identifiers
- 991005542268207891
- Copyright
- © 2006 Lippincott Williams & Wilkins
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.66 HIV
- 1.66.1372 HIV Comorbidities
- Web Of Science research areas
- Immunology
- Infectious Diseases
- ESI research areas
- Immunology