Longitudinal study of herpes simplex virus type 2 infection using viral dynamic modelling

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Abstract
Objectives: Rates of reactivation of herpes simplex virus type 2 (HSV-2) change over time and these changes affect transmission and clinical management strategies. We conducted a longitudinal study of HSV-2 infection to quantify rates of change in HSV-2 reactivation, mucosal shedding and recurrences of genital lesions, using a newly available model of HSV within-host dynamics. Methods: A cohort of 18 women was studied at two time periods spaced 2 years apart. The cohort provided daily mucosal swabs for HSV PCR analysis for 10 weeks during each time period and recorded recurrences in diaries. We fit the model of HSV dynamics to the mucosal shedding data using Bayesian methods to produce estimates of HSV reactivation, shedding and longitudinal rates of change. The model was validated using a separate group of 67 individuals. Results: According to the viral dynamic modelling results, rates of HSV-2 reactivation from latency in the ganglia varied >10-fold among the women, and were estimated to be ⩾10% higher than rates of mucosal shedding episodes for many individuals. The mucosal shedding associated with each reactivation typically lasted 1–3 days. Reactivation frequency was estimated to be declining by three reactivations a year on average. The median number of recurrences, based on patient diaries, declined from 6.8 per year to 2.1 per year over the 2-year period. Conclusions: Rates of HSV-2 reactivation, shedding and recurrence generally decline over time but remain high in some individuals 4–5 years after primary infection. Viral dynamic modelling provides quantification of HSV infection that cannot be obtained by other methods.