Measuring levels of mitochondrial DNA in the blood over three to four years cannot predict the development of lipoatrophy, nor any other drug toxicities associated with the nucleoside analogue class of antiretrovirals, according to an extensive study by researchers at the Center for AIDS Research at Case Western Reserve University in Cleveland, United States. The findings suggest that the development of tests to measure plasma mitochondrial DNA levels may have little clinical value.
The research group, led by Grace McComsey of Case Western Reserve University, recruited 54 HIV-positive patients receiving nucleoside analogue (NRTI) treatment, 33 NRTI-naïve HIV-positive patients and 48 age-matched HIV-negative volunteers as control groups. Forty-nine HIV-positive patients participated in a longitudinal study with a median of two assessments of mitochondrial DNA levels during 24 months of follow-up.
At entry to the study the median duration of NRTI treatment was 58 months. Two-thirds of the NRTI-treated patients had clinical lipoatrophy and 17% had clinical evidence of mitochondrial toxicity (four cases of peripheral neuropathy, two cases of lactic acidosis and two cases of symptomatic hyperlactatemia).
Although NRTI-treated HIV-positive individuals were found to have significantly lower mitochondrial DNA levels when compared to HIV-negative controls, there was no correlation between the extent of mitochondrial DNA depletion in blood and the presence of lipoatrophy or symptomatic mitochondrial toxicity. Indeed, one third of NRTI-treated patients showed an increase in mitochondrial DNA levels during the follow-up period.
Two patients showed evidence of mutations in mitochondrial DNA after NRTI treatment, but the implications of these mutations are unknown.
The authors note that they did not investigate the possibility that platelet contamination of blood specimens might lead to inaccurate mitochondrial DNA measurements in this study, and that the follow-up period was relatively short.
McComsey G et al. Extensive investigations of mitochondrial DNA genome in treated HIV-infected subjects: beyond mitochondrial DNA depletion. J Acquir Immune Defic Syndr 39: 181-188, 2005.