Ribavirin (Copegus / Rebetol / Virazole)

Ribavirin (Copegus / Rebetol / Virazole) is an antiviral drug that is active against a range of viruses. It is an approved and effective treatment for hepatitis C when used in combination with interferon alfa (IntronA / Viraferon / Roferon-A) or peginterferon alfa (Pegasys / PegIntron / ViraferonPeg) in HIV-positive and –negative patients. Ribavirin is a nucleoside analogue that disrupts viral replication. Initially, it was investigated as an anti-HIV treatment but research was halted due to poor results.

The recommended dosage for people under 75kg is two 200mg capsules in the morning and three capsules in the evening. For people over 75kg, three capsules are taken both morning and night. Ribavirin should be taken with food.

Based on current research, treatment is recommended for at least 24 weeks, with an additional 24 weeks of treatment for individuals who had high baseline viral loads or genotype 1, which is associated with a poorer response to treatment. Age, male sex and extent of fibrosis may also be considered in extension of treatment. For details of the effectiveness of ribavirin as a treatment for hepatitis C, see Hepatitis C.

Ribavirin has caused severe birth defects in animal studies and women taking ribavirin are advised to use contraception. It has also caused sperm mutations in animal studies and couples should avoid pregnancy while male partners are taking ribavirin. Pregnancy should be avoided until seven months after completing treatment with ribavirin. Breastfeeding is not recommended during treatment with ribavirin.

Ribavirin is not recommended for use in individuals with severe liver damage or autoimmune hepatitis. A kidney check should be performed before a patient starts ribavirin.

Ribavirin with interferon alfa may cause a range of side-effects including headache, fatigue, muscle ache and fever, as well as flu-like symptoms. The most common side-effect of ribavirin is anaemia, which can be treated with epoetin alfa.1 Other side-effects include mood swings, irritability, anxiety, insomnia, abdominal pain, nervousness, breathlessness, rash, hair loss, dry skin, nausea, diarrhoea, loss of appetite, dizziness and weight loss.

Unusual or serious side-effects such as chest pain, persistent cough, changes in heart beat, confusion, depression and blood in the urine should be reported to a doctor immediately.

Ribavirin reduces the concentrations of AZT (zidovudine, Retrovir) and d4T (stavudine, Zerit).2 HIV viral load should be closely monitored if ribavirin is being taken concurrently with AZT or d4T, and a change in treatment considered if viral load rises.

There is preliminary evidence that ribavirin may increase the risk of metabolic side-effects, such as pancreatitis, liver abnormalities, lactic acidosis, glucose intolerance and weight loss, associated with the nucleoside reverse transcriptase inhibitors (NRTIs), particularly ddI (didanosine, Videx / VidexEC) and d4T.3 4 5 6 7 8 These metabolic side-effects have been attributed to mitochondrial toxicity.

Ribavirin does not interact with any currently available protease inhibitors or non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Despite some promising early studies, ribavirin has been shown to have little or no direct effect against HIV.9 10 11 12 13 14 15 However, test-tube studies and preliminary research in humans has shown that ribavirin can act in a similar way to hydroxycarbamide (Hydrea), increasing the potency and effectiveness of ddI.16 17 Although there is little or no interest in further testing ribavirin as a direct treatment for HIV, research into ribavirin in combination with ddI is continuing.

References

  1. Sulkowski MS et al. Epoetin alfa once weekly improves anemia in HIV / hepatitis C virus-coinfected patients treated with interferon / ribavirin: a randomized controlled trial. J Acquir Immune Defic Syndr 39: 504-507, 2005
  2. Vogt MW et al. Ribavirin antagonizes the effect of azidothymidine on HIV replication. Science 235: 1376-1379, 1987
  3. Japour AJ et al. A phase-I study of the safety, pharmacokinetics, and antiviral activity of combination didanosine and ribavirin in patients with HIV-1 disease. AIDS Clinical Trials Group 231 Protocol Team. J Acquir Immune Defic Syndr Hum Retrovirol 13: 235-246, 1996
  4. Van Dyke R et al. A phase I dose-escalating study of the combination of didanosine plus ribavirin in HIV-infected children. Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, abstract I-6, 1998
  5. Bani-Sadr F et al. Risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus-coinfected patients during interferon plus ribavirin-based therapy. J Acquir Immune Defic Syndr 40: 47-52, 2005
  6. Moreno A et al. High rate of didanosine-related mitochondrial toxicity in HIV / HCV-coinfected patients receiving ribavirin. Antivir Ther 9: 133-138, 2004
  7. Lafeuillade A et al. Increased mitochondrial toxicity with ribavirin in HIV / HCV coinfection. Lancet 357: 280-281, 2001
  8. Fleischer R et al. Evidence suggesting mitochondrial toxicity in HIV / HCV co-infected patients receiving ribavirin and didanosine. Tenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract P763, 2003
  9. Crumpacker C et al. Ribavirin treatment of the acquired immunodeficiency syndrome (AIDS) and the acquired-immunodeficiency-syndrome-related complex (ARC). A phase I study shows transient clinical improvement associated with the suppression of the human immunodeficiency virus and enhanced lymphocyte proliferation. Ann Intern Med 107: 664-674, 1987
  10. Spanish Ribavirin Trial Group. Comparison of ribavirin and placebo in CDC group III human immunodeficiency virus infection. Lancet 338: 6-9, 1991
  11. Roberts RB et al. A phase 1 study of ribavirin in human immunodeficiency virus-infected patients. J Infect Dis 162: 638-642, 1990
  12. Roberts RB et al. A multicentre clinical trial of oral ribavirin in HIV infected patients with lymphadenopathy. J Acquir Immune Defic Syndr 3: 884-892, 1990
  13. Vernon AA et al. Multicenter clinical trial of oral ribavirin in symptomatic HIV-infected patients. J Acquir Immune Defic Syndr 6: 32-41, 1993
  14. Roberts RB et al. A multicenter clinical trial of oral ribavirin in HIV-infected people with lymphadenopathy: virologic observations. Ribavirin-LAS Collaborative Group. AIDS 4: 67-72, 1990
  15. Snell N et al. A meta-analysis of placebo-controlled clinical trials of ribavirin in patients with HIV infection. Eighth International Conference on AIDS, Amsterdam, abstract PuB7523, 1992
  16. Balzarini J et al. Mechanism of the potentiating effect of ribavirin on the activity of 2',3'-dideoxyinosine against HIV. J Biol Chem 266: 21509-21514, 1991
  17. de Clercq E. Ribavirin for HIV. Lancet 338: 450-451, 1991

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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.