Chapter 178

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 ...

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