BACKGROUND: Non-invasive diagnostic assays to evaluate mitochondrial toxicity could have significant clinical utility for HIV-infected individuals on antiretroviral therapy (ART). METHODS: This study compared the ratio of mitochondrial to nuclear DNA determined by quantitative polymerase chain reaction (qPCR) to the ratio of mitochondrial to nuclear-encoded proteins by flow cytometry, in peripheral blood mononuclear cells from 73 HIV-infected individuals with and without risk factors for mitochondrial toxicity. RESULTS: PCR detected similar mitochondrial/nuclear DNA in HIV-infected individuals without a history of ART, and those receiving ART with lipodystrophy, lipoatrophy, or a history of suspected lactic acidosis. However, the ratio was significantly greater in ART-untreated compared to those receiving either stavudine or didanosine. In contrast, flow cytometry did not detect any differences in mitochondrial/nuclear protein (Lin et al., Cytometry B 2009;76B:181-190). There was no correlation between the assays (rho = -0.05, P = 0.65). CONCLUSIONS: Assessment of the mitochondrial/nuclear DNA ratio by qPCR performed better than the mitochondrial/nuclear-encoded protein ratio by flow cytometry to detect adverse effects of nucleoside analogs on mitochondria.
BACKGROUND: Non-invasive diagnostic assays to evaluate mitochondrial toxicity could have significant clinical utility for HIV-infected individuals on antiretroviral therapy (ART). METHODS: This study compared the ratio of mitochondrial to nuclear DNA determined by quantitative polymerase chain reaction (qPCR) to the ratio of mitochondrial to nuclear-encoded proteins by flow cytometry, in peripheral blood mononuclear cells from 73 HIV-infected individuals with and without risk factors for mitochondrial toxicity. RESULTS: PCR detected similar mitochondrial/nuclear DNA in HIV-infected individuals without a history of ART, and those receiving ART with lipodystrophy, lipoatrophy, or a history of suspected lactic acidosis. However, the ratio was significantly greater in ART-untreated compared to those receiving either stavudine or didanosine. In contrast, flow cytometry did not detect any differences in mitochondrial/nuclear protein (Lin et al., Cytometry B 2009;76B:181-190). There was no correlation between the assays (rho = -0.05, P = 0.65). CONCLUSIONS: Assessment of the mitochondrial/nuclear DNA ratio by qPCR performed better than the mitochondrial/nuclear-encoded protein ratio by flow cytometry to detect adverse effects of nucleoside analogs on mitochondria.
Authors: Grace A McComsey; Denise M Paulsen; J Tyler Lonergan; Siegrid M Hessenthaler; Charles L Hoppel; Vanessa C Williams; Robin L Fisher; Catherine L Cherry; Cathy White-Owen; Katherine A Thompson; Steve T Ross; Jaime E Hernandez; Lisa L Ross Journal: AIDS Date: 2005-01-03 Impact factor: 4.177
Authors: Julio S G Montaner; Hélène C F Côté; Marianne Harris; Robert S Hogg; Benita Yip; Jennifer W Chan; P Richard Harrigan; Michael V O'Shaughnessy Journal: J Acquir Immune Defic Syndr Date: 2003-09 Impact factor: 3.731