Effect of treatment interruption monitored by CD4 cell count on mitochondrial DNA content in HIV-infected patients: a prospective study.
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.
Mussini
Cristina
C
Clinic of Infectious and Tropical Diseases, University of Modena and Reggio Emilia, Modena, Italy. crimuss@unimo.it
Pinti
Marcello
M
Bugarini
Roberto
R
Borghi
Vanni
V
Nasi
Milena
M
Nemes
Elisa
E
Troiano
Leonarda
L
Guaraldi
Giovanni
G
Bedini
Andrea
A
Sabin
Caroline
C
Esposito
Roberto
R
Cossarizza
Andrea
A
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000097:blood* / Q000187:drug effects; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D019562:Viral Load
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors