Role of animal models in selecting antiviral combinations for clinical studies

Although experimental viral infections in animals have been used extensively in the development of antiviral drugs used as monotherapy, they have not been utilized widely for evaluation of combination chemotherapy. One of the major reasons for the lack of use of animal models is that for the diseases that are the main target for combination therapy, AIDS and hepatitis B and C infections, there is a lack of suitable models for these diseases. In contrast, most combination studies in animal models have been directed against herpes simplex virus infections but there are relatively few patients available who would benefit from combination therapy over single agent therapy. In between those two extremes are the cytomegalovirus infections. While there are animal models available that have been predictive of efficacy in humans and there are sufficient patients available, the use of antiviral combinations in animal models and in humans have begun only recently. At the present time there is not enough information available to establish the predictability for any of the animal models for efficacy of combinations of antiviral agents.