Limitations of Antiviral Drugs
As mentioned above, clinical use of the currently available antiviral drugs is limited by toxic side effects. There are also some general limitations inherent in antiviral chemotherapy (Table 52-4).
First, the more selective the antiviral drug the narrower its antiviral activity spectrum.
Second, since antiviral drugs target steps in virus replication, the latent phases characteristic of some viral (i.e. herpesviral) infections are not amenable to chemotherapy. This is particularly relevant for herpesvirus and retrovirus infections. Thus, eradication of latent virus infections is not feasible currently.
Third, antiviral drug treatment should be started early, before irreversible tissue damage occurs. Such timely treatment is not possible without early and accurate diagnosis, which is difficult for many viral infections (such as infections of the respiratory tract).
Fourth, perhaps inevitably for a specific antimicrobial agent, there is the risk of emergence of drug-resistant virus strains. This has been most dramatically demonstrated in AIDS patients from whom drug-resistant human immunodeficiency virus strains have been isolated against virtually all the drugs that have been tried so far. In the same patients treated with acyclovir for HSV or VZV infections, acyclovir-resistant HSV or VZV strains have been detected. The fact that these HSV and VZV mutants, as well as the resistant HIV strains, retained full susceptibility to other antiviral agents is reassuring. These findings indicate that on the one hand, combination therapy should be studied, particularly for the prevention of HIV drug resistance, and that, on the other hand, attempts to develop new antiviral agents should continue unabated.
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