Effects of antiviral usage on transmission dynamics of herpes simplex virus type 1 and on antiviral resistance: Predictions of mathematical models

Herpes simplex virus type 1 (HSV-1) causes recurrent herpes labialis (RHL), a common disease afflicting up to 40% of adults worldwide. Mathematical mo dels are used to analyze the effect of antiviral treatment on the transmiss ion of, and the prevalence of drug resistance in, HSV-1 in the United State s. Three scenarios are analyzed: no antiviral use, the current level of use , and a substantial increase in nucleoside analogue use, such as might occu r if topical penciclovir were available over-the-counter for the treatment of RBL, A basic model predicts that present level of nucleoside analogue us e has a negligible effect on HSV-1 transmission and that even if use of top ical penciclovir for (RHL) increased substantially, the overall prevalence of infectious HSV-1 is unlikely to be reduced by more than 5%. An expanded model, which allows for acquired resistance and includes immunocompromised hosts and other more realistic features, predicts that current antiviral us e is unlikely to lead to any noticeable increase in resistance. If antivira l use increases, the resulting rise in resistance in the population will de pend primarily on the probability that immunocompetent hosts will acquire p ermanent resistance upon treatment. This probability is known to be small, but its exact value remains uncertain. If acquired resistance occurs less t han once per 2,500 treated episodes, then in the community at Large, the fr equency of HSV-1 resistance is predicted to increase slowly, if at all (rem aining below 0.5% for >50 years), even with extensive nucleoside analogue u se. If acquired resistance emerges in 1 of 625 treated episodes (the maximu m of an approximate 95% confidence interval derived from the results of sev eral studies of resistance in treated hosts), then the prevalence of infect ion with resistant HSV-1 could rise from about 0.2% to 1.5 to 3% within 50 years. The limitations of existing data on acquired resistance and the pote ntial impact of acquired resistance if it occurs are discussed, and strateg ies are suggested for enhancing information on acquired resistance. The pre dictions of this model contrast with the more rapid increases in antimicrob ial resistance anticipated by models and observed for other pathogenic bact eria and viruses. The reasons for these contrasting predictions are discuss ed.