Adherence and drug resistance: predictions for therapy outcome

We combine standard pharmacokinetics with an established model of viral rep lication to predict the outcome of therapy as a function of adherence to th e drug regimen. We consider two types of treatment failure: failure to elim inate the wild-type virus, and the emergence of drug-resistant virus. Speci fically, we determine the conditions under which resistance dominates as a result of imperfect adherence. We derive this result for both single- and t riple-drug therapies, with attention to conditions which favour the emergen ce of viral strains that are resistant to one or more drugs in a cocktail. Our analysis provides quantitative estimates of the degree of adherence nec essary to prevent resistance. We derive results specific to the treatment o f human immunodeficiency virus infection, but emphasize that our method is applicable to a range of viral or ether infections treated by chemotherapy.