An IV formulation of zanamivir is being evaluated in clinical trials and is available for compassionate use from the manufacturer. A long-acting neuraminidase inhibitor, laninamivir octanoate, may retain activity against oseltamivir-resistant virus. DAS181 is a host-directed antiviral agent with activity against influenza and parainfluenza that acts by removing the virus receptor, sialic acid, from adjacent glycan structures.
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 (see Chapter 61).
In addition to oral administration for HCV infection in combination with interferon alfa (see Antihepatitis Agents), aerosolized ribavirin is administered by nebulizer (20 mg/mL for 12–18 hours continuously per day) to children and infants with severe respiratory syncytial virus (RSV) bronchiolitis or pneumonia to reduce the severity and duration of illness. Systemic absorption is low (<1%). Aerosolized ribavirin may cause conjunctival or bronchial irritation and the aerosolized drug may precipitate on contact lenses. Ribavirin is teratogenic and embryotoxic. Health care workers and pregnant women should be protected against extended inhalation exposure.
Ribavirin has in vitro activity against a number of viruses, including Lassa, West Nile, measles, influenza, and parainfluenza. However, clinical data regarding effectiveness are lacking.
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 bronchopulmonary 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 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.
Agents under investigation for the treatment or prophylaxis of patients with RSV infection include small molecule inhibitors that interfere with RSV fusion through interaction with the F protein of RSV (e.g., GS-5806) and the oral nucleoside analog ALS-008176.
Imiquimod is an immune response modifier shown to be effective in the topical treatment of external genital and perianal warts (ie, condyloma acuminatum; see Chapter 61). 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 molluscum contagiosum but is not licensed in the USA 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.