Article
Mitochondrial dysfunction induced by HIV postexposure prophylaxis
Mitochondriale Dysfunktion durch HIV Postexpositionsprophylaxe
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Published: | June 2, 2010 |
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Objectives: Both combination antiretroviral therapy (cART) and HIV itself may cause mitochondrial toxicity. To better define the specific influence of cART we monitored the decrease in mitochondrial transmembrane potential (ΔΨm) in HIV uninfected patients receiving HIV post exposure prophylaxis (PEP).
Methods: Twenty patients undergoing PEP and 9 individuals not receiving PEP were enrolled in the study. Blood was drawn before start of PEP (wk 0), after 2 and 4 weeks of PEP (wk 2 and wk 4), and 8 weeks after finishing PEP (wk 12) from available patients. FACS analysis of ΔΨm was performed by staining isolated peripheral blood mononuclear cells (PBMC) with JC-1, a fluorescent dye indicating mitochondrial transmembrane potential. Apoptotic cells were identified by Annexin-V-FITC and propidium iodide (PI) staining. Eighteen of the 20 PEP patients received a combination of emtricitabine, tenofovir and lopinavir/ritonavir.
Results: Measurements of ΔΨm and apoptosis at the different timepoints before (wk 0), during (wk 2, wk 4), and after PEP (wk 12) are shown in the figure. ΔΨm in isolated PBMC changed significantly over the 12 week course of observation (p=0.017). A significant decrease was found during the 4 weeks of PEP (p=0.0084). During the time period without PEP between 4 and 12 weeks ΔΨm increased significantly (p=0.025) to levels comparable to baseline. This was also found in the subgroup of the 18 patients receiving a combination of emtricitabine, tenofovir and lopinavir/ritonavir (p=0.04). No significant difference was found in the apoptosis rates during and 8 weeks after PEP (p=0.46).
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Conclusions: A four week course of HIV-PEP using cART mainly consisting of tenofovir, emtricitabine, and lopinavir/ritonavir induced mitochondrial toxicity by causing a significant decrease in ΔΨm in PBMC; it did not affect the apoptosis rate of PBMC. Mitochondrial damage of longterm HIV cART may be significant even using newer agents thought to be less toxic, such as tenofovir and emtricitabine.