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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e318250455e
Basic and Translational Science

Mitochondrial Evolution in HIV-Infected Children Receiving First- or Second-Generation Nucleoside Analogues

Morén, Constanza BS*,†; Noguera-Julian, Antoni MD, PhD; Garrabou, Glòria BS, PhD*,†; Catalán, Marc BS*,†; Rovira, Núria MD; Tobías, Ester LA*,†; Cardellach, Francesc MD, PhD*,†; Miró, Òscar MD, PhD*,†; Fortuny, Clàudia MD, PhD

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Background: Highly active antiretroviral therapy (HAART) and HIV-related mitochondrial toxicity lead to several adverse effects and have become a major issue, especially in children. The main goal in the treatment of HIV-infected children is to maximize cost-effectiveness while minimizing toxicity. We aimed to study the evolution of mitochondrial parameters over time in children receiving different types antiretroviral regimens.

Methods: We followed-up 28 HIV-infected children receiving HAART including either first-generation nucleoside reverse transcriptase inhibitors (1gNRTIs; didanosine, zidovudine, or stavudine; n = 15) or second-generation NRTIs (2gNRTIs; the remaining drugs; n = 13) for a period of 2 years for their immunovirological and mitochondrial status, and compared these subjects with a group of untreated HIV-infected patients (n = 10) and uninfected controls (n = 27). We measured T-lymphocyte CD4+ content (flow cytometry), viral load (real-time polymerase chain reaction), and lactate levels (spectrophotometry); we assessed mtDNA content (real-time polymerase chain reaction), mitochondrial protein levels (Western blot), oxidative stress, mitochondrial mass, and electron transport chain function (spectrophotometry) in peripheral blood mononuclear cells.

Results: At the second time point, lactate levels were significantly higher in children on 1gNRTIs compared with those receiving 2gNRTIs (1.28 ± 0.08 vs. 1.00 ± 0.07 mmol/L, respectively; P = 0.022). MtDNA content was similar among all HIV-infected groups and significantly lower than in healthy controls at baseline. Oxidative stress tended to increase over time in all the groups, with no differences among them. However, a significant decrease in cytochrome c oxidase activity was found over time in HIV-infected patients; this decline was greater in the 1gNRTIs group.

Conclusions: HIV infection and the use of 1gNRTIs caused greater mitochondrial damage than 2gNRTIs over time. The higher lactate levels and the significant decrease observed in cytochrome c oxidase activity argue against the use of 1gNRTIs in HIV-infected children when an alternative is available, in accordance with international recommendations.

© 2012 Lippincott Williams & Wilkins, Inc.


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