Mitochondrial toxic effects and ribavirin

Salmon‐Céron, Dominique; Chauvelot‐Moachon, Laurence; Abad, S.; Silbermann, Benjamin; Sogni, Philippe

doi:10.1016/s0140-6736(00)04921-7

Cited by 89 publications

(51 citation statements)

References 3 publications

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“…Recently, reports of fatal development of lactic acidosis and/or pancreatitis have appeared in HIV/HCV-coinfected patients receiving concomitantly RBV with either d4T and/or ddI, particularly in the setting of cirrhosis. [19][20][21][22] Although liver histology was not available in many of our patients, fibrosis in different extent was uniformly demonstrated, with liver cirrhosis in up to 40% of biopsied cases, in agreement with other reports that have proven advanced liver fibrosis in a high proportion of HIV/HCV-coinfected patients. [23][24][25] This circumstance should have favored the recognition of any of these complications in our series.…”

Section: Discussionsupporting

confidence: 91%

Treatment of Chronic Hepatitis C in HIV-Infected Patients with Interferon α-2b Plus Ribavirin

Pérez‐Olmeda

Soriano

Asensi

et al. 2003

AIDS Research and Human Retroviruses

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One hundred six HIV-infected patients with chronic hepatitis C virus (HCV) infection were randomized to receive ribavirin (RBV) 400 mg bid plus interferon a-2b (IFN-a) at two different doses, 3 mU tiw (control arm) or 5 mU daily for the first 6 weeks, followed by 3 mU tiw until completing 6 months of therapy (induction arm). All patients had CD4 counts above 350 cells/ml and 89% were taking antiretroviral therapy. Adverse effects leading to treatment discontinuation occurred in 12.3% of patients, a rate quite similar to that seen in HCV-monoinfected patients. Negative serum HCV-RNA values (,60 IU/ml) were recorded in 24.7% and 35.5% of patients at 3 and 6 months of therapy. However, in the intent-to-treat analysis, sustained response was reached by only 16% of patients (22.4% in the on-treatment analysis). No differences between treatment arms were noticed. Patients with HCV genotypes 2 or 3 had a 7-fold higher response rate than those with HCV genotypes 1 or 4. Therefore, early, end-of-treatment, and sustained response rates are lower in HIV/HCV-coinfected patients treated with RBV/IFN-a combination therapy. Since HCV-related liver disease is currently one of the leading causes of morbidity and mortality among HIV-infected patients, new treatment options are urgently needed for coinfected individuals.

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Section: Discussionsupporting

confidence: 91%

Treatment of Chronic Hepatitis C in HIV-Infected Patients with Interferon α-2b Plus Ribavirin

Pérez‐Olmeda

Soriano

Asensi

et al. 2003

AIDS Research and Human Retroviruses

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“…Blood was obtained at days 4,8,12, and 16 pi and the serum stored at -80 °C. TNF-α was detected in the serum by QuantiKine quantitative sandwich enzyme immunoassay (EIA) (R&D Systems, Minneapolis, MN) according to the manufacturer's instructions.…”

Section: Detection Of Tnf-α In Serum By Enzyme-linked Immunosorbent Amentioning

confidence: 99%

“…Some nucleoside analogs have been found to be highly inhibitory in animal models [9] , but ribavirin is the only antiviral agent known to be successful against HTNV infections in clinical trails [10] . However, the utilization of ribavirin is limited by its myelosuppression and toxicity [11][12][13] . No antiviral agent has been approved by the Food and Drug Administration (FDA) to treat HFRS [5] .…”

Section: Introductionmentioning

confidence: 99%

Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro

et al. 2009

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Aim: Arbidol is an immunomodulator that was first developed in Russia. In this study, we report the antiviral activity of arbidol against Hantaan virus (HTNV) in vitro and in vivo. Methods: The antiviral activity of arbidol in vitro was determined by plaque-forming assay, ranging from 0.5 to 8 μg/mL. To investigate whether arbidol has an antiviral effect in vivo, suckling BALB/c mice infected with HTNV were treated with arbidol at 24 h before infection with a 5, 10 or 20 mg·kg -1 ·d -1 , once per day, for 10 days. On day 12 and 28 post infection (pi), histopathological changes and viral antigen were detected. On days 4, 8, 12, and 16 pi, the viral load of target organs and serum TNF-α levels of arbidol-treated animals were determined. Results: Arbidol was found to have potent inhibitory activity against HTNV when added in vitro before or after viral infection, with a 50% inhibitory concentration (IC 50 ) of 0.9 and 1.2 μg/mL, respectively. The 50% lethal dose (LD 50 ) of arbidol for suckling mice was 78.42 mg·kg -1 ·d -1 . Oral administration of arbidol increased both survival rate and mean time to death (MTD). Treatment with arbidol reduced histopathological changes, decreased viral load and viral antigen levels, and modulated the level of serum TNF-α. Conclusion: Arbidol has the ability to elicit protective antiviral activity against HTNV in vivo and in vitro.

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“…Both of these side effects appear to be linked to the use of HIV protease inhibitors. [1][2][3][4] However, the broad spectrum of toxicities associated with nucleoside analogue reverse transcriptase inhibitors (NRTIs), which result in mitochondrial dysfunction, suggests that NRTIs can also cause lipodystrophy syndrome. 5 Mitochondrial toxicity is related to the inhibition of DNA polymerase-g, an essential enzyme for the replication of mitochondrial DNA (mtDNA), by NRTIs.…”

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confidence: 99%

Prospective evaluation of blood concentration of mitochondrial DNA as a marker of toxicity in 157 consecutively recruited untreated or HAART-treated HIV-positive patients

Chiappini

Teicher

Saffroy

et al. 2004

Laboratory Investigation

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Highly active antiretroviral therapy (HAART) can cause mitochondrial toxicity. The concentration of mitochondrial DNA (mtDNA) in peripheral blood cells has been reported to be a marker of this toxicity. However, these observations are controversial and were drawn from small series. Thus, we analysed the value of blood mtDNA as a marker of mitochondrial toxicity in a large cohort of human immunodeficiency virus (HIV)-infected out-patients during routine clinical evaluations. Real-time quantitative PCR was used to determine the mtDNA to nuclear DNA (nDNA) ratio in peripheral blood mononuclear cells from 157 consecutive HIV-1-infected patients (13 naive, 144 receiving HAART) and 30 HIV-1-uninfected patients. The mtDNA to nDNA ratio was significantly lower in both groups of HIV-infected patients than in the control group. No significant difference was observed between treated and naive HIV-infected patients. Lactataemia was significantly lower in controls than in the group of HIV-treated patients. None of the treated patients had lactataemia 45 mmol/l or bicarbonates o20 mmol/l. Triglyceride levels were significantly higher in the HAART-treated patients than in the nontreated patients. Clinical symptoms of lipodystrophy were observed in 62 HAART-treated patients. These symptoms were not associated with an abnormal mtDNA to nDNA ratio or plasma triglyceride concentration. The mtDNA to nDNA ratio was lower in DDI/D4T-treated patients than in AZT/3TC-treated patients. In conclusion, there are no obvious links between the mtDNA to nDNA ratio in peripheral mononuclear cells and any clinical symptoms or lactate level. Thus, the mtDNA to nDNA ratio in leukocytes does not seem to be an accurate marker of mild and/or long-term mitochondrial toxicity.

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Mitochondrial toxic effects and ribavirin

Cited by 89 publications

References 3 publications

Treatment of Chronic Hepatitis C in HIV-Infected Patients with Interferon α-2b Plus Ribavirin

Treatment of Chronic Hepatitis C in HIV-Infected Patients with Interferon α-2b Plus Ribavirin

Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro

Prospective evaluation of blood concentration of mitochondrial DNA as a marker of toxicity in 157 consecutively recruited untreated or HAART-treated HIV-positive patients

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