Interferon alfa

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Interferon alfa is a natural protein produced by the human body in response to infection. It has some direct antiviral effects and stimulates the immune system to fight foreign organisms.

Interferon alfa is best known as a treatment for viral hepatitis. Effectiveness of interferon alfa against hepatitis C virus is improved when taken in combination with ribavirin (Copegus / Rebetol / Virazole). It is a licensed treatment for some forms of cancer, including non-Hodgkin’s lymphoma and Kaposi’s sarcoma. It is also an approved treatment for genital warts and for hepatitis B, and there is some evidence that it can prevent infection with severe acute respiratory syndrome (SARS).1 2

The precise role of interferon alfa in HIV infection is unclear. It can inhibit the virus in test-tube studies, and recent research in people has shown significant anti-HIV activity. During the early days of treatment research, the reputation of interferon as a treatment for HIV was undermined by difficulties with administration and an association between a type of interferon alfa called endogenous acid-labile interferon alfa and the onset of symptoms. Now researchers are turning to interferon as a possible treatment for HIV / hepatitis C co-infected individuals and as a salvage therapy for HIV.

Types of interferon alfa

Genetic engineering techniques have allowed several companies to mass-produce interferon alfa. This is known as recombinant human interferon alfa, or by the abbreviations rhIFN or rIFN-alfa. It is marketed under tradenames such as IntronA or Viraferon (made by Schering-Plough) and Roferon-A (made by Roche).

Interferon alfa N3 (Alferon N) is another form of interferon alfa, derived from human leukocytes and containing multiple species of interferon alfa. It has shown promising in vitro action against HIV.

A new form of interferon alfa, called peginterferon alfa, is now licensed in Europe and the United States. When coated with polyethylene glycol (or ‘pegylated’), the clearance of interferon alfa from the body is delayed, allowing the compound to be administered weekly instead of three times a week. Peginterferon alfa is marketed as Pegasys by Roche and as PegIntron and ViraferonPeg by Schering-Plough.

Taking it

Interferon alfa is usually given by intramuscular injection. These injections are only moderately painful and most people can manage to do them themselves at home. Subcutaneous injections can sometimes be an alternative.

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

Interferon alfa for viral hepatitis

Interferon alfa treatment for hepatitis C consists of 24- or 48-week courses of treatment. Side-effects may be very severe, although they tend to reduce as treatment continues.

In Europe, peginterferon alfa is licensed for the treatment of hepatitis C that is proven by biopsy in adults. The results of the APRICOT, ACTG A5071 and RIBAVIC trials have demonstrated that peginterferon alfa is superior to interferon alfa when combined with ribavirin in HIV-positive individuals with hepatitis C.3 4 5 This led to the approval of Pegasys in combination with ribavirin for HIV-positive people in February 2005.

Peginterferon alfa plus ribavirin is also effective in treating acute hepatitis C infection. In a trial of 25 HIV-positive patients, 71% of the patients had undetectable hepatitis C viral loads six months after finishing treatment.6 For more information on hepatitis C treatment, see Hepatitis C.

Interferon alfa is also a licensed treatment for chronic hepatitis B virus infection, with peginterferon being more effective in clinical trials. Recent studies have shown that in patients who are hepatitis B e antigen-positive, peginterferon alfa is a more effective first-line treatment than 3TC (lamivudine, Epivir) or the combination of 3TC and peginterferon alfa.7 8 For more information, see Hepatitis B.

Interferon alfa for HIV

Trials of interferon alfa as an anti-HIV treatment have produced inconsistent results. In several studies, people receiving interferon alfa have experienced a sharp drop in their CD4 cell count, lending weight to the view that interferon alfa may contribute to the immune system damage seen in people with HIV.9 10 However, a small study investigating the safety of peginterferon alfa has found that a low daily dose may have pronounced anti-HIV effects.11 These findings suggest that interferon alfa may be a useful addition to antiretroviral therapy, although long-term studies are needed.

A study in primary HIV infection has shown that when peginterferon alfa is added to antiretroviral therapy for 14 weeks, it reduces the size of the HIV reservoir, as well as increasing HIV-specific immune responses and slowing viral rebound during a subsequent treatment interruption.12 Single-drug treatment with peginterferon alfa has also boosted CD4 cell counts and lowered viral load in five people with early stage HIV infection, although monotherapy is known to be an inferior treatment strategy compared with combination antiretroviral therapy.13

Interferon alfa has also been used in a salvage study for people with HIV after promising results from high dose interferon alfa in three co-infected people.14

Studies have shown that intravenous interferon alfa can be helpful in treating Kaposi’s sarcoma, especially among people with higher CD4 cell counts.15

In 1990, much publicity was given to claims that a type of interferon alfa absorbed in very low doses through the mouth marketed as Kemron greatly improved immune function, increased CD4 cell counts and in some cases caused HIV-positive people to become HIV-negative.16 17 However, much research has taken place to attempt to confirm or refute these findings and none of these studies have been able to find any benefit.18 19 20 21

Side-effects

Injected interferon alfa usually causes side-effects which resemble the symptoms of influenza, such as shivering, muscle aches and feelings of fatigue. It can also lead to insomnia and neutropenia - a shortage of neutrophils, immune cells that attack fungi and bacteria. A major side-effect of interferon alfa therapy is depression, which can be treated with antidepressant drugs.22

Peginterferon alfa has a similar pattern of side-effects, although mild to moderate injection site reactions and dose reductions due to neutropenia are more common. Visual side-effects including loss of colour vision, cotton wool spots and cataracts have been reported among HIV-positive people taking peginterferon alfa with ribavirin.23

References

  1. Haagmans BL et al. Pegylated interferon protects type 1 pneumocytes against SARS coronavirus infection in macaques. Nat Med 10: 290-293, 2004
  2. Brockmeyer NH et al. Treatment of condylomata acuminata with pegylated interferon alfa-2b in HIV-infected patients. Eur J Med Res 11: 27-32, 2006
  3. Chung R et al. Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis in HIV-coinfected persons. N Engl J Med 351: 451-459, 2004
  4. Carrat F et al. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA 292: 2839-2848, 2004
  5. Torriani FJ et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. New Engl J Med 351: 438-450, 2004
  6. Dominguez S et al. Efficacy of early treatment of acute hepatitis C infection with pegylated interferon and ribavirin in HIV-infected patients. AIDS 20: 1157-1161, 2006
  7. Lau GKK et al. Peginterferon alfa-2a, lamivudine, and the combination for HbeAg-positive chronic hepatitis B. N Engl J Med 352: 2682-2695, 2005
  8. Chan HLY et al. A randomized, controlled trial of combination therapy for chronic hepatitis B: comparing pegylated interferon-alpha2b and lamivudine with lamivudine alone. Ann Intern Med 142: 240-250, 2005
  9. Vento S et al. Rapid decline of CD4+ cells after IFN-alpha treatment in HIV-1 infection. Lancet 341, 958-959, 1993
  10. Soriano V et al. CD4+ T-lymphocytopenia in HIV-infected patients receiving interferon therapy for chronic hepatitis C. AIDS 8: 1621-1622, 1994
  11. Sypsa V et al. HIV-1 dynamics in vivo after administration of pegylated interferon alpha-2b (PEG-intron). Fifth International Congress on Drug Therapy in HIV Infection, Glasgow, abstract P7, 2000
  12. Emilie D et al. Early control of HIV replication in primary HIV-1 infection treated with antiretroviral drugs and pegylated IFN alpha: results from the Primoferon A (ANRS 086) Study. AIDS 15: 1435-1437, 2001
  13. Schugt I et al. Pegylated interferon alfa-2b: a new therapeutic option in the treatment of early-stage HIV infection. Tenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 59, 2003
  14. Wensing A et al. Is interferon-alpha the solution for HIV-infected patients who have failed on HAART? 39th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, abstract 2208, 1999
  15. Rozenbaum et al. Long-term follow-up of 120 patients with AIDS-related Kaposi's sarcoma treated with interferon alpha-2a. J Invest Dermatol 95: 161-165, 1990
  16. Koech DK et al. Efficacy of KEMRON (low dose oral natural human interferon alpha) in the management of HIV-1 infection and acquired immune deficiency syndrome (AIDS). East Afr Med J 67: SS64-SS70, 1990
  17. Koech DK et al. Low dose oral alpha-interferon therapy for patients seropositive for human immunodeficiency virus type-1 (HIV-1). J Mol Biother 2: 91-95, 1990
  18. Kaiser G et al. Low-dose oral natural human interferon-alpha in 29 patients with HIV-1 infection: a double-blind, randomized, placebo-controlled trial. AIDS 6: 563-569, 1992
  19. Sperber SJ et al. Low-dose oral recombinant interferon-alpha A in patients with HIV-1 infection: a blinded pilot study. AIDS 7: 693-697, 1993
  20. Hulton MR et al. Randomized, placebo-controlled, double-blind study of low-dose oral interferon-alpha in HIV-1 antibody positive patients. J Acquir Immune Defic Syndr 5: 1084-1090, 1992
  21. Katabira E et al. Lack of efficacy of low dose oral interferon alfa in symptomatic HIV-1 infection. Sex Transm Infect 74: 265-270, 1998
  22. Laguno M et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV coinfected patients. AIDS 18: F27-F36, 2004
  23. Farel C et al. Serious ophthalmic pathology compromising vision in HCV / HIV co-infected patients treated with peginterferon alpha-2b and ribavirin. AIDS 18: 1805-1809, 2004

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