Tissue-Specific Associations between Mitochondrial DNA levels and current treatment status in HIV infected individuals

Catherine L. Cherry, David Nolan, Ian R. James, Elizabeth J. McKinnon, Simon A. Mallal, Michelle Gahan, Luxshimi Lal, Justin McArthur, Steven L. Wesselingh

Research output: Contribution to journalArticle

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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 < or = 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
Original languageEnglish
Pages (from-to)435-440
Number of pages6
JournalJournal of Acquired Immune Deficiency Syndromes
Volume42
Issue number4
DOIs
Publication statusPublished - 2006
Externally publishedYes

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Mitochondrial DNA
HIV
Didanosine
Reverse Transcriptase Inhibitors
Blood Cells
Therapeutics
Nucleosides
Fats
Demography
Stavudine
Subcutaneous Fat
Real-Time Polymerase Chain Reaction
Linear Models

Cite this

Cherry, Catherine L. ; Nolan, David ; James, Ian R. ; McKinnon, Elizabeth J. ; Mallal, Simon A. ; Gahan, Michelle ; Lal, Luxshimi ; McArthur, Justin ; Wesselingh, Steven L. / Tissue-Specific Associations between Mitochondrial DNA levels and current treatment status in HIV infected individuals. In: Journal of Acquired Immune Deficiency Syndromes. 2006 ; Vol. 42, No. 4. pp. 435-440.
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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 < or = 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",
author = "Cherry, {Catherine L.} and David Nolan and James, {Ian R.} and McKinnon, {Elizabeth J.} and Mallal, {Simon A.} and Michelle Gahan and Luxshimi Lal and Justin McArthur and Wesselingh, {Steven L.}",
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Cherry, CL, Nolan, D, James, IR, McKinnon, EJ, Mallal, SA, Gahan, M, Lal, L, McArthur, J & Wesselingh, SL 2006, 'Tissue-Specific Associations between Mitochondrial DNA levels and current treatment status in HIV infected individuals', Journal of Acquired Immune Deficiency Syndromes, vol. 42, no. 4, pp. 435-440. https://doi.org/10.1097/01.qai.0000224974.67962.ce

Tissue-Specific Associations between Mitochondrial DNA levels and current treatment status in HIV infected individuals. / Cherry, Catherine L.; Nolan, David; James, Ian R.; McKinnon, Elizabeth J.; Mallal, Simon A.; Gahan, Michelle; Lal, Luxshimi; McArthur, Justin; Wesselingh, Steven L.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 42, No. 4, 2006, p. 435-440.

Research output: Contribution to journalArticle

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T1 - Tissue-Specific Associations between Mitochondrial DNA levels and current treatment status in HIV infected individuals

AU - Cherry, Catherine L.

AU - Nolan, David

AU - James, Ian R.

AU - McKinnon, Elizabeth J.

AU - Mallal, Simon A.

AU - Gahan, Michelle

AU - Lal, Luxshimi

AU - McArthur, Justin

AU - Wesselingh, Steven L.

PY - 2006

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N2 - 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 < or = 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

AB - 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 < or = 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

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M3 - Article

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SP - 435

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JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

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