Predicting the emergence of drug-resistant HSV-2: new predictions

We generated theoretical drug-resistant HSV-2 strains that were attenuated (in comparison with drug-sensitive strains) in both infectivity and ability to reactivate. We then used a transmission model to predict the emergence and transmission of drug-resistant HSV-2 in the immunocompetent population assuming a high usage of antivirals.Our predictions are an order of magnitude lower than previous predictions; we predict that even after 25 years of high antiviral usage only 5 out of 10,000 immunocompetent individuals will be shedding drug-resistant virus. Furthermore, after 25 years, 52 cases of HSV-2 would have been prevented for each prevalent case of drug-resistant HSV-2.The predicted levels of drug-resistant HSV-2 for the immunocompetent population are so low that it seems unlikely that cases of drug-resistant HSV-2 will be detected.Mathematical models can be used as health policy tools to predict the emergence and transmission of antiviral resistance [1-5]. These models have predicted, that if treatment rates are high, that high levels of antiviral resistance to HIV will arise very quickly; for example, 42% of HIV cases in San Francisco are predicted to be infected with drug-resistant strains by 2005 [3,4]. These theoretical predictions have been compared with empirical data, and shown to be valid [4,6]. In stark contrast to the HIV predictions, it has been predicted that high usage of antivirals to treat Herpes Simplex Virus type 2 (HSV-2) would only lead to low levels of resistance (in immunocompetent populations) [1,2]. These predictions were based upon the assumption that drug-resistant strains of HSV-2 would be less infectious than drug-sensitive strains, but that the drug-resistant strains would not be impaired in their reactivation ability. However, recent experience with drug-resistant variants has shown that the majority of these variants are deficient in the expression of thymidine kinase [7-9], a phenotype that is known to be associated with a reduced a