Interferon beta is a natural protein produced by the human body in response to infection. It is one of three classes of interferon (the others are interferon alfa and interferon gamma). Artificial (recombinant) interferon beta is produced by genetically engineered bacteria.

Current use

Interferon beta is a licensed drug for treating certain categories of multiple sclerosis. Its use by people with HIV is experimental. Test tube studies have shown that interferon beta has anti-HIV effects and the combination of interferon beta plus AZT (zidovudine, Retrovir) is synergistic. However, clinical trials to date have found no evidence of any antiviral benefits from beta interferon treatment. It has also been used experimentally to treat advanced Kaposi's sarcoma (KS), with little success.

Interferon beta is given by injection. Possible side-effects include fever, headache, chills, pain in the joints (arthralgia) or muscles (myalgia), dizziness, sweating, nausea, fatigue, leukopenia, thrombocytopenia, pain at injection site, loss of appetite, diarrhoea, vomiting, elevation of serum liver enzyme levels, transient sight disturbances, seizures, confusion and formation of antibodies to interferon.

Key research

Miles (1998) enrolled 15 people in a dosing study of interferon beta which was given as subcutaneous injection at doses of 22.5, 45 or 90 million units daily plus 500 mg AZT daily. 2 people had complete resolution of KS and 3 had stable disease for 24-44 weeks.

In vitro studies have shown that interferon beta stimulates NK cell cytotoxicity and enhances antigen expression. Hartshorn and Yamamoto reported that beta interferon inhibits HIV. Michaelis reported that interferon beta protects infected PBMC cultures from virus-mediated cytopathology and killing and inhibits HIV replication as measured by reverse transcriptase activity.

Miles studied the efficacy of high doses (90 million or 180 million international units/day) of interferon beta in a sequential sample of 39 people with biopsy-proven Kaposi's sarcoma. Treatment was well-tolerated with the major toxicities being local reaction at the injection site and flu-like symptoms. KS tumour response was minimal. However, there was evidence of anti-HIV effects; in 8/19 people with HIV p24 antigen levels of more than 50 pg/mL at entry the level decreased by more than 50% with treatment, although changes were transient.

Oka reported that four weeks' treatment with interferon beta did not affect the number of HIV proviruses in the blood of 11 treated people in a clinical trial as measured by quantitative PCR.

An interim analysis was conducted by the sponsor on a multicentre phase III double-blind placebo-controlled trial of interferon beta for people with ARC or AIDS and CD4 cell counts <200 cells/mm³. No improvements in immunological and virological parameters or clinical events were reported. Due to disease progression, local skin reactions or systematic symptoms (fevers, malaise) and the availability of other agents through competing protocols, approximately 30% of the subjects have withdrawn from the study.

References

Hartshorn KL et al. Activity of interferons alpha, beta, and gamma against human immunodeficiency virus replication in vitro. AIDS Research and Human Retroviruses 3(2):125-133, 1987.

Michaelis B et al. HIV replication can be blocked by recombinant human interferon beta. AIDS 3(1): 27-31, 1989.

Miles SA et al. Beta-interferon therapy in patients with poor-prognosis Kaposi's sarcoma related to AIDS: a phase II trial with preliminary evidence of antiviral activity and low incidence of opportunistic infections. Annals of Internal Medicine 112(8): 582-589, 1990.

Miles S et al. Open-label phase I study of combination therapy with zidovudine and interferon-beta in patients with AIDS-related Kaposi's sarcoma. AIDS Clinical Trials Group Protocol 057. Cytokines Cell Mol Ther 491: 17-23, 1998.

Oka S et al. HIV DNA copies as a virologic marker in a clinical trial with beta-interferon. Journal of AIDS 5(7): 707-711, 1992.

Yamamoto JK et al. Inhibition of human immunodeficiency virus type 1 replication by human interferons alpha, beta and gamma. Arch Immunol Ther Exp (Warsz) 41(3-4): 185-191, 1993.