BACKGROUND: HIV infection per se and HAART can alter mitochondrial functionality, leading to a decrease in mitochondrial DNA content. OBJECTIVE: To evaluate whether treatment interruption monitored by CD4 cell count can restore mitochondrial DNA content in peripheral blood lymphocytes. METHODS: Mitochondrial DNA content was measured in platelet-free CD4 and CD8 T cells by real-time polymerase chain reaction; flow cytometry was used to identify and quantify activated CD4 and CD8 T lymphocytes. RESULTS: The 30 patients had been treated for a mean of 107 months (range, 27-197). Median CD4 cell count at discontinuation was 702 cells/microl (range, 547-798). Median observational time from HAART discontinuation was 11.3 months (range, 4-26). Discontinuation of treatment provoked significant increases in mitochondrial DNA in CD8 T cells, which started only 6 months after therapy discontinuation [5.12 copies/cell per month from 0 to 6 months (P = 0.37) and 26.96 copies/cell per month from 6 to 12 months (P < 0.0001)]. CONCLUSIONS: This study is the first showing that mitochondrial DNA content can increase in peripheral blood lymphocytes during treatment interruption, but only after at least 6 months of interruption. Consequently, interruptions of shorter periods, whether by clinician or patient decision, are unlikely to allow restoration of mitochondrial DNA and so decrease HAART-related toxicity.
BACKGROUND:HIV infection per se and HAART can alter mitochondrial functionality, leading to a decrease in mitochondrial DNA content. OBJECTIVE: To evaluate whether treatment interruption monitored by CD4 cell count can restore mitochondrial DNA content in peripheral blood lymphocytes. METHODS: Mitochondrial DNA content was measured in platelet-free CD4 and CD8 T cells by real-time polymerase chain reaction; flow cytometry was used to identify and quantify activated CD4 and CD8 T lymphocytes. RESULTS: The 30 patients had been treated for a mean of 107 months (range, 27-197). Median CD4 cell count at discontinuation was 702 cells/microl (range, 547-798). Median observational time from HAART discontinuation was 11.3 months (range, 4-26). Discontinuation of treatment provoked significant increases in mitochondrial DNA in CD8 T cells, which started only 6 months after therapy discontinuation [5.12 copies/cell per month from 0 to 6 months (P = 0.37) and 26.96 copies/cell per month from 6 to 12 months (P < 0.0001)]. CONCLUSIONS: This study is the first showing that mitochondrial DNA content can increase in peripheral blood lymphocytes during treatment interruption, but only after at least 6 months of interruption. Consequently, interruptions of shorter periods, whether by clinician or patient decision, are unlikely to allow restoration of mitochondrial DNA and so decrease HAART-related toxicity.
Authors: H Samji; T E Taha; D Moore; A N Burchell; A Cescon; C Cooper; J M Raboud; M B Klein; M R Loutfy; N Machouf; C M Tsoukas; J S G Montaner; R S Hogg Journal: HIV Med Date: 2014-09-01 Impact factor: 3.180
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Authors: Jelena Misic; Dusanka Milenkovic; Ali Al-Behadili; Xie Xie; Min Jiang; Shan Jiang; Roberta Filograna; Camilla Koolmeister; Stefan J Siira; Louise Jenninger; Aleksandra Filipovska; Anders R Clausen; Leonardo Caporali; Maria Lucia Valentino; Chiara La Morgia; Valerio Carelli; Thomas J Nicholls; Anna Wredenberg; Maria Falkenberg; Nils-Göran Larsson Journal: Nucleic Acids Res Date: 2022-08-10 Impact factor: 19.160
Authors: Annalinda Pisano; Bruna Cerbelli; Elena Perli; Maria Pelullo; Valentina Bargelli; Carmela Preziuso; Massimiliano Mancini; Langping He; Matthew G D Bates; Joaquin R Lucena; Paola Lilla Della Monica; Giuseppe Familiari; Vincenzo Petrozza; Chiara Nediani; Robert W Taylor; Giulia d'Amati; Carla Giordano Journal: Cardiovasc Pathol Date: 2015-09-30 Impact factor: 2.185