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Cherry Catherine L.; Gahan, Michelle E.; McArthur, Justin C.; Lewin, Sharon R.; Hoy, Jennifer F.; Wesselingh, Steven L.
JAIDS Journal of Acquired Immune Deficiency Syndromes: July 1st, 2002
doi: 10.1097/01.QAI.0000017962.22053.0E
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Objectives:Nucleoside reverse transcriptase inhibitors (NRTIs), particularly dideoxynucleoside analogs (ddNs), used in the treatment of HIV, inhibit mitochondrial DNA polymerase γ 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.

Address correspondence and reprint requests to Catherine L Cherry, Department of Infectious Diseases and Microbiology, The Alfred Hospital, Commercial Rd, Prahran 3181, Victoria, Australia; e-mail kate.cherry@med.monash.edu.au

C.L. Cherry and S.L. Wesselingh are supported by the National Health and Medical Research Council (NHMRC); J.C. McArthur by NS 26643; and S.R. Lewin by the NHMRC, the Ian Potter Foundation, and by equipment grants from the Wellcome Trust and ANZ trustees.

Manuscript received December 11, 2001; accepted March 25, 2002.

© 2002 Lippincott Williams & Wilkins, Inc.