Exposure to dideoxynucleosides is reflected in lowered mitochondrial DNA in subcutaneous fat.
OBJECTIVE
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.
Department of Infectious Diseases and Microbiology, The Alfred Hospital, Melbourne, Australia. kate.cherry@med.monash.edu.au
Catherine L
CL
Cherry
Michelle E
ME
Gahan
Justin C
JC
McArthur
Sharon R
SR
Lewin
Jennifer F
JF
Hoy
Steven L
SL
Wesselingh
D000273:Adipose Tissue / Q000737:chemistry*; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology*; D004272:DNA, Mitochondrial / Q000032:analysis*; D015224:Dideoxynucleosides / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D012867:Skin / Q000737:chemistry
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors