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Mitochondrial DNA depletion in HIV-infected patients is enhanced with chronic hepatitis C and treatment with pegylated interferon plus ribavirin
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C de Mendoza1, M Sanchez-Conde1, E Timmermans2, M Buitelaar2, P Fernandez-Casas1, M P de Baar2, J Gonzalez-Lahoz1, V Soriano1
1Hospital Carlos III, Madrid, Spain; 2Primagen, Amsterdam, Netherlands
Poster B3313
Mitochondrial damage seems to be responsible for many of the toxicities associated with the long-term use of nucleoside reverse transcriptase inhibitors. These adverse effects, mainly lipoatrophy, peripheral neuropathy, hepatic steatosis (fatty liver), lactic acidosis, and type II diabetes could be even more pronounced in patients with Hepatitis C virus (HCV) and HIV coinfection. There is no information about the possible additive effect of HCV on mtDNA depletion in HIV/HCV-coinfected individuals.
mtDNA was measured in PBMCs (from blood as opposed t tissue samples) collected from 192 individuals classified in 4 groups:
--107 HIV-pos/HCV-pos, COINFECTED
--56 HIV-pos/HCV-neg, HIV+ alone
--18 HIV-neg/HCV-pos HCV+ alone
--11 HIV-neg/HCV-neg. HCV & HIV NEGATIVE (controls)
A duplex real-time NASBA assay was used to quantify mtDNA on maximal platelet-depleted specimens and experiments were run in duplicate. The mtDNA copy number per cell was estimated taking as reference the nuclear DNA copy number and results expressed as mtDNA copies/cell.
RESULTS
The mean mtDNA values for the:
11 HIV-neg/HCV-neg persons was 757 copies/cell,
while it was 428, 349 and 296 for HIV-pos, HCV-pos and HIV/HCV-coinfected individuals, respectively (p<0.001).
No significant differences were observed when comparing patients with HIV and HCV monoinfections,
but coinfected individuals showed a significantly lower mtDNA copy number than HIV-monoinfected patients (p<0.001) or subjects with HCV-monoinfection (p=0.089).
In a subset of 18 patients with HIV/HCV-coinfection, treatment with pegylated interferon + ribavirin produced a further reduction in mtDNA (mean value, 189 copies/cell; p=0.009). Interestingly, all these subjects received RBV in addition to antiretroviral drugs.
AUTHOR CONCLUSIONS
HIV and HCV may independently cause mtDNA depletion in PBMC.
Coinfection may result in a higher mtDNA depletion.
The administration of interferon plus ribavirin may further enhance mtDNA depletion.
These findings may explain the greater risk of lipoatrophy of antiretroviral therapy in HIV+ patients with HCV coinfection and why anti-HCV therapy may aggravate this effect.
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