Effect of treatment interruption monitored by CD4 cell count on mitochondrial DNA content in HIV-infected patients: a prospective study

C Mussini, M Pinti, R Bugarini, V Borghi, M Nasi… - Aids, 2005 - journals.lww.com
C Mussini, M Pinti, R Bugarini, V Borghi, M Nasi, E Nemes, L Troiano, G Guaraldi, A Bedini
Aids, 2005journals.lww.com
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 …
Abstract
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/μl (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.
Lippincott Williams & Wilkins