M. Lipsitch et al., Effects of antiviral usage on transmission dynamics of herpes simplex virus type 1 and on antiviral resistance: Predictions of mathematical models, ANTIM AG CH, 44(10), 2000, pp. 2824-2835
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.