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].