870 
Influence of Hepatitis C Virus Infection on Mitochondrial DNA Depletion in HIV-co-infected Patients
Carmen De Mendoza*1, N Zahonero1, P Barreiro1, M De Baar2, L Capa1, J Benito1, and V Soriano1
1Hosp Carlos III, Madrid, Spain and 2Primagen, Amsterdam, The Netherlands
Background: The metabolic stress derived
from high levels of virus replication in both HIV and hepatitis C virus (HCV) infections
seems to result in mitochondrial damage and mtDNA
depletion, which is enhanced in HCV/HIV-co-infected patients.
Following introduction of HAART, there is improvement in the mtDNA amount
accompanying HIV-RNA suppression,
although the use of some nucleoside
analogs (stavudine, didanosine, dideoxycytidine) subsequently reverses this benefit by inhibiting DNA polymerase g. Information on the effect of
treatment of HCV infection on mtDNA
is scarce, and conflicting results have been
reported.
Methods: We analyzed 43 HCV/HIV-co-infected patients (32 on HAART and 11 without ART) who initiated treatment with pegylated interferon (pegINF) plus ribavirin (RBV). The amount of mtDNA
was measured in peripheral blood mononuclear cells (PBMC) using Retina Mitox (Primagen) at baseline,
24 weeks of therapy, and 6 months after treatment
discontinuation.
Results: An inverse correlation
between serum HCV RNA titers and mtDNA
content in PBMC was recognized at baseline
in all patients, which was significant
for patients on HAART (r = –0.463;
p = 0.023). There
was a significant increase in mtDNA during HCV treatment in both ART-naïve and -experienced patients, when HCV replication was suppressed. However, it declined again
to baseline values upon HCV treatment discontinuation. Subjects on HAART receiving stavudine showed significantly lower mtDNA values
at baseline than the rest
(319 vs 199 copies/cell, respectively; p <0.01).
|
|
On HAART (n=32)
|
No
HAART (n=11)
|
|
Male (gender)
|
24 (75%)
|
8 (73%)
|
|
Mean
age (years)
|
43
|
41
|
|
Mean
baseline CD4 count (cells/mL)
|
596
|
527
|
|
Mean
baseline HIV RNA (log)
|
<1.7
|
3.8 *
|
|
Mean
baseline HCV RNA (log)
|
4.9
|
6.5 *
|
|
HCV
genotype (1 / 2-3 / 4)
|
19 / 11 / 2
|
8 / 3 / 0
|
|
Mean
baseline mtDNA (copies/cell):
HCV
genotype 1-4 vs 2-3
|
320 vs
287 *
|
343 vs
225
|
|
Mean
mtDNA (copies/cell):
Baseline
On HCV therapy
After HCV therapy
|
284
347
267 #
|
275
336 #
200 #
|
|
D mtDNA
after HCV therapy (copies/cell)
Sustained viral response vs
non-sustained
viral response
|
+52.3 vs –22.6
|
NA
|
* p <0.05 between groups. # p <0.01 within
group
Conclusions: Treatment of chronic
hepatitis C in HIV+ patients is associated with
a significant improvement
in the mtDNA content in PBMC. Both ART-naïve as well as patients concomitantly taking ARTseem to benefit from
this effect, suggesting that there is no deleterious
synergistic effect of RBV when taken
along with nucleoside analogs other than didanosine.
|
