Exposure to dideoxynucleosides is reflected in lowered mitochondrial DNA in subcutaneous fat
Author
Cherry, CL; Gahan, ME; McArthur, JC; Lewin, SR; Hoy, JF; Wesselingh, SLDate
2002-07-01Source Title
JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMESPublisher
LIPPINCOTT WILLIAMS & WILKINSUniversity of Melbourne Author/s
Lewin, SharonAffiliation
Microbiology And ImmunologyMetadata
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Journal ArticleCitations
Cherry, C. L., Gahan, M. E., McArthur, J. C., Lewin, S. R., Hoy, J. F. & Wesselingh, S. L. (2002). Exposure to dideoxynucleosides is reflected in lowered mitochondrial DNA in subcutaneous fat. JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 30 (3), pp.271-277. https://doi.org/10.1097/01.QAI.0000017962.22053.0E.Access Status
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C1 - Journal Articles Refereed
Abstract
OBJECTIVES: Nucleoside reverse transcriptase inhibitors (NRTIs), particularly dideoxynucleoside analogs (ddNs), used in the treatment of HIV, inhibit mitochondrial DNA polymerase gamma in vitro. Mitochondrial DNA (mtDNA) depletion is proposed as the underlying mechanism of many of the in vivo side effects of these agents. A reliable and valid laboratory test to detect this is not yet available. The objective of this study was to correlate tissue mtDNA quantification in HIV-infected patients with exposure to nucleoside analogs. METHODS: 60 HIV-infected adults underwent detailed clinical assessment and blood and tissue sampling. Clinical and antiretroviral treatment details were correlated with results of plasma lactate assays, and real-time polymerase chain reaction quantification of mtDNA in peripheral blood mononuclear cells (PBMCs) and subcutaneous fat from the lower limb. RESULTS: Forty-nine (82%) subjects were on combination antiretroviral therapy. Of these, 33 (55%) were currently receiving one or more ddNs (stavudine, didanosine, or zalcitabine). mtDNA in subcutaneous fat was lower in subjects currently on ddNs than in those not taking ddNs (mean [log10] 2.47 vs. 2.74, p =.002). Plasma lactate was somewhat higher in subjects currently taking ddNs than those on no antiretroviral treatment (median 1.5 vs. 1.0, p =.03), but was not significantly different in either of these groups compared with subjects on other NRTIs. mtDNA in PBMCs did not vary with treatment status. CONCLUSIONS: mtDNA in subcutaneous fat was significantly reduced in patients currently taking ddNs. mtDNA in PBMCs was independent of patient exposure to NRTIs.
Keywords
Cellular Immunology; Immune System and AllergyExport Reference in RIS Format
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