Mitochondrial DNA depletion in HIV-infected patients with chronic hepatitis C and effect of pegylated interferon plus ribavirin therapy.
BACKGROUND
The metabolic stress derived from high levels of virus replication in both HIV and hepatitis C virus (HCV) infections results in mitochondrial DNA depletion, which seems to be enhanced in co-infected patients. The use of nucleoside analogues to treat HIV infection may further increase mtDNA depletion by inhibiting gamma DNA polymerase. Information on the impact of therapy with pegylated interferon (pegIFN) plus ribavirin on mtDNA is scarce and conflicting results have been reported.


METHODS
Fifty-nine HCV/HIV-co-infected patients (43 on and 16 off antiretroviral therapy) who initiated treatment with pegIFN plus ribavirin were retrospectively analysed. The amount of mtDNA in peripheral blood mononuclear cells (PBMC) was measured at baseline and at the end of HCV therapy.


RESULTS
Mean baseline serum HCV-RNA was 5.8 log IU/ml and 56% of patients were infected by HCV genotype 1. An inverse correlation between serum HCV-RNA levels and PBMC mtDNA content was recognized at baseline (r = -0.370; P = 0.006). HCV-RNA suppression at the end of HCV therapy was associated with a significant increase in mtDNA, particularly in patients with baseline HCV-RNA levels greater than 6 log IU/ml (+61 mtDNA copies/cell) and in subjects not taking antiretroviral therapy (+133 mtDNA copies/cell).


CONCLUSIONS
HCV replication correlates with the extent of mtDNA depletion in PBMC, and treatment of chronic hepatitis C is associated with a significant improvement in mtDNA content. This benefit, however, is not recognized when HCV medications are used along with antiretroviral therapy, probably because of a deleterious interaction of these drugs on mitochondria.
de Mendoza
Carmen
C
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
Martin-Carbonero
Luz
L
Barreiro
Pablo
P
de Baar
Michel
M
Zahonero
Natalia
N
Rodriguez-Novoa
Sonia
S
Benito
José Miguel
JM
González-Lahoz
Juan
J
Soriano
Vincent
V
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004272:DNA, Mitochondrial / Q000097:blood* / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load
D000998:Antiviral Agents; D004272:DNA, Mitochondrial; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a