The field of antiviral therapy—both the number of antiviral drugs and our understanding of their optimal use—historically has lagged behind that of antibacterial drug treatment, but significant progress has been made in recent years on new drugs for several viral infections. The development of antiviral drugs poses several challenges. Viruses replicate intracellularly and often employ host cell enzymes, macromolecules, and organelles for synthesis of viral particles. Therefore, useful antiviral compounds must discriminate between host and viral functions with a high degree of specificity; agents without such selectivity are likely to be too toxic for clinical use.
Significant progress has also been made in the development of laboratory assays to assist clinicians in the appropriate use of antiviral drugs. Phenotypic and genotypic assays for resistance to antiviral drugs are becoming more widely available, and correlations of laboratory results with clinical outcomes are being better defined. Of particular note has been the development of highly sensitive and specific methods that measure the concentration of virus in blood (virus load) and permit direct assessment of the antiviral effect of a given drug regimen in that host site. Virus load measurements have been useful in recognizing the risk of disease progression in patients with certain viral infections and in identifying patients for whom antiviral chemotherapy might be of greatest benefit. As with any in vitro laboratory test, results are highly dependent on (and likely to vary with) the laboratory techniques employed.
Information regarding the pharmacokinetics of some antiviral drugs, particularly in diverse clinical settings, is limited. Assays to measure the concentrations of these drugs, especially of their active moieties within cells, are primarily research procedures and are not widely available to clinicians. Thus, there are relatively few guidelines for adjusting dosages of antiviral agents to maximize antiviral activity and minimize toxicity. Consequently, clinical use of antiviral drugs must be accompanied by particular vigilance with regard to unanticipated adverse effects.
Like that of other infections, the course of viral infections is profoundly affected by an interplay of the pathogen with a complex set of host defenses. The presence or absence of preexisting immunity, the ability to mount humoral and/or cell-mediated immune responses, and the stimulation of innate immunity are important determinants of the outcome of viral infections. The state of the host's defenses needs to be considered when antiviral agents are used or evaluated.
As with any therapy, the optimal use of antiviral compounds requires a specific and timely diagnosis. For some viral infections, such as herpes zoster, the clinical manifestations are so characteristic that a diagnosis can be made on clinical grounds alone. For other viral infections, such as influenza A, epidemiologic information (e.g., the documentation of a community-wide outbreak) can be used to make a presumptive diagnosis with a high degree of accuracy. However, for most of the remaining viral infections, including herpes simplex encephalitis, cytomegaloviral infections other than retinitis, and enteroviral infections, diagnosis on clinical grounds alone cannot be accomplished with certainty. For such infections, rapid viral diagnostic techniques are of great importance. Considerable progress has also been made in recent years in the development of such tests, which are now widely available for a number of viral infections.
Despite these complexities, the efficacy of a number of antiviral compounds has been clearly established in rigorously conducted and controlled studies. As summarized in Table 178-1, this chapter reviews the antiviral drugs that are currently approved or are likely to be considered for approval in the near future for use against viral infections other than those caused by HIV. Antiretroviral drugs are reviewed in Chap. 189.
Table 178-1 Antiviral Chemotherapy and Chemoprophylaxis
| Save Table
Table 178-1 Antiviral Chemotherapy and Chemoprophylaxis
|Influenza A and B: Treatment||Oseltamivir||Oral|
Adults: 75 mg bid × 5 d
Children 1–12 years: 30–75 mg bid, depending on weight,a × 5 d
|When started within 2 days of onset in uncomplicated disease, zanamivir and oseltamivir reduce symptom duration by 1.0–1.5 and 1.3 d, respectively. Their effectiveness in prevention or treatment of complications is unclear, although some analyses suggest that oseltamivir may reduce the frequency of respiratory tract complications and hospitalizations. Oseltamivir's side effects of nausea and vomiting can be reduced in frequency by drug administration with food. Zanamivir may exacerbate bronchospasm in patients with asthma. Amantadine and rimantadine are not recommended for routine use unless antiviral susceptibilities are known because of widespread resistance in A/H3N2 viruses since 2005–2006 and in pandemic A/H1N1 viruses in 2009–2010. Their efficacy in treatment of uncomplicated disease caused by sensitive viruses has been similar to that of neuraminidase inhibitors.|
|Zanamivir||Inhaled orally||Adults and children ≥7 years: 10 mg bid × 5 d|
Adults: 100 mg qd or bid × 5–7 d
Children 1–9 years: 5 mg/kg per day (maximum, 150 mg/d) × 5–7 d
|Rimantadineb||Oral||100 mg qd or bid × 5–7 d in adults|
|Influenza A and B: Prophylaxis||Oseltamivir||Oral|
Adults: 75 mg/d
Children ≥1 year: 30–75 mg/d, depending on weighta
|Prophylaxis must be continued for the duration of exposure and can be administered simultaneously with inactivated vaccine. Unless the sensitivity of isolates is known, neither amantadine nor rimantadine is currently recommended for prophylaxis or therapy.|
|Zanamivir||Inhaled orally||Adults and children ≥5 years: 10 mg/d|
|Amantadineb or rimantadineb||Oral|
Adults: 200 mg/d
Children 1–9 years: 5 mg/kg per day (maximum, 150 mg/d)
|RSV infection||Ribavirin||Small-particle aerosol||Administered 12–18 h/dfrom reservoir containing 20 mg/mL × 3–6 d||Use of ribavirin is to be "considered" for treatment of infants and young children hospitalized with RSV pneumonia and bronchiolitis, according to the American Academy of Pediatrics.|
|CMV disease||Ganciclovir||IV||5 mg/kg bid × 14–21 d; then 5 mg/kg per day as maintenance dose||Ganciclovir, valganciclovir, foscarnet, and cidofovir are approved for ...|
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