Other Antiviral Agents

OTHER ANTIVIRAL AGENTS

INTERFERONS

Interferons have been studied for numerous clinical indications. In addition to HBV and HCV infections (see Antihepatitis Agents), intralesional injection of interferon alfa-2b or alfa-n3 may be used for treatment of condylomata acuminata .

RIBAVIRIN

In addition to oral administration for HCV infection in combina-tion with interferon alfa (see Antihepatitis Agents), aerosolized ribavirin is administered by nebulizer (20 mg/mL for 12–18 hours per day) to children and infants with severe respiratory syncytial virus (RSV) bronchiolitis or pneumonia to reduce the severity and dura-tion of illness. Aerosolized ribavirin has also been used to treat influ-enza A and B infections but has not gained widespread use. Systemic absorption is low (< 1%). Aerosolized ribavirin is generally well toler-ated but may cause conjunctival or bronchial irritation. Health care workers should be protected against extended inhalation exposure. The aerosolized drug may precipitate on contact lenses.

Intravenous ribavirin decreases mortality in patients with Lassa fever and other viral hemorrhagic fevers if started early. High con-centrations inhibit West Nile virus in vitro, but clinical data are lacking. Clinical benefit has been reported in cases of severe measles pneumonitis and certain encephalitides, and continuous infusion of ribavirin has decreased virus shedding in several patients with severe lower respiratory tract influenza or parainfluenza infections. At steady state, cerebrospinal fluid levels are about 70% of those in plasma.

PALIVIZUMAB

Palivizumab is a humanized monoclonal antibody directed against an epitope in the A antigen site on the F surface protein of RSV. It is licensed for the prevention of RSV infection in high-risk infants and children, such as premature infants and those with bronchopul-monary dysplasia or congenital heart disease. A placebo-controlled trial using once-monthly intramuscular injections (15 mg/kg) for 5 months beginning at the start of the RSV season demonstrated a 55% reduction in the risk of hospitalization for RSV in treated patients, as well as decreases in the need for supplemental oxygen, the illness severity score, and the need for intensive care. Although resistant strains have been isolated in the laboratory, no resistant clinical isolates have yet been identified. Potential adverse effects include upper respiratory tract infection, fever, rhinitis, rash, diarrhea, vomiting, cough, otitis media, and elevation in serum aminotransferase levels.

A number of other agents are under investigation for the treat-ment or prophylaxis of patients with RSV infection, including the RNA interference (RNAi) therapeutic ALN-RSV01, the human-ized monoclonal antibody motavizumab, and the benzodiazepine RSV604.

IMIQUIMOD

Imiquimod is an immune response modifier shown to be effective in the topical treatment of external genital and perianal warts (ie, condyloma acuminatum;). The 5% cream is applied three times weekly and washed off 6–10 hours after each application. Recurrences appear to be less common than after ablative therapies. Imiquimod may also be effective against mol-luscum contagiosum but is not licensed in the United States for this indication. Local skin reactions are the most common adverse effect; these tend to resolve within weeks after therapy. However, pigmentary skin changes may persist. Systemic adverse effects such as fatigue and influenza-like syndrome have occasionally been reported.