RESISTANCE TO ANTIVIRALS

Some viral infections can be successfully controlled with currently available antiviral drugs. Unfortunately, as has been the case for antibiotics, resistance to antiviral drugs has been reported (see Table 2-6). Two examples of resistance are discussed below. Potentially effective new drugs undergoing preclinical and clinical testing may replace some antivirals that have been rendered unusable as a result of excessive patterns of resistance.

Despite the efforts of researchers to discover new, effective antiviral drugs, very few ever reach the point at which they become available to those who need them. Thousands of compounds may be screened before a single candidate with desirable antiviral properties and acceptable tolerance is found. Drugs that are potentially useful against viral infections fit into three categories: those that inactivate viruses (virucides); those that inhibit the replication of viruses within their host cells (antivirals); and those that work indirectly by augmenting or modifying the host's immune response to viral invasion (immunomodulators) (Hayden and Douglas, 1990). There are no clinically practical virucidal drugs at this time, since those currently available are toxic to host cells as well as viruses. Unlike those antibiotics that are bactericidal and can rid the patient of the organism, current antivirals only suppress viral replication. Ultimately, control of the viral infection relies on the individual's immune response.

TABLE 2-6 Antiviral Drugs for Which Resistance Has Been Demonstrated

Antiviral Agent

Antiviral Spectrum

Acyclovir

Herpes simplex virus

 

Varicella-zoster virus

Amantadine/rimantidine

Influenza A

Dideoxycytidine

Human immunodeficiency virus-1

Dideoxyinosine

Human immunodeficiency virus-1

Foscarnet

Cytomegalovirus

 

Herpes simplex virus

Ganciclovir

Cytomegalovirus

 

Herpes simplex virus

Idoxuridine (topical)

Herpes simplex virus

Trifluridine (topical)

Herpes simplex virusa

Vidarabine

Herpes simplex virusa

Zidovudine

Human immunodeficiency virus-1

a Resistance to these drugs can be demonstrated in the laboratory but has not yet been documented in clinical isolates.

SOURCE: F. Hayden, Associate Professor of Internal Medicine and Pathology, Department of Internal Medicine, University of Virginia Hospital.



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