Infectious Diseases in Obstetrics and Gynecology Table 2: Percent of Days with HSV-2 Viral Shedding. Population ITTC P-value % Reduction Valacyclovir (n = 52) 25 3.0 (4.6) 0–17 27 2.9 (6.5) 0–29 52 2.9 (5.6) 0–29 30 2.6 (4.3) 2.4 (4.8) 0.6 (1.7) 31 (60) 41 (79) >68 Placebo (n = 52) 27 14.3 (16.6) 12.6 (17.4) 0–68 25 0–61 52 0–68 35 13.5 (16.9) 14.9 (18.3) 11 (15.1) 2.4 (4.4) 15 (29) 27 (52) 61 Other Eﬃcacy Parameters Valacyclovir (n = 52) Placebo (n = 52) < .001 < .001 78 83 P-value <.001 .014 <.001 .003 .010 4 Period 1 Period 2 Overall ITT Period 1 ITTC Percent days with subclinical shedding, Mean (SD %) Percent days with clinical shedding, Mean (SD %) Subjects with no Shedding, n (%) Proportion of subjects recurrencefree, n (%) Median time to ﬁrst genital herpes recurrencea (days) a First treatment period. n Mean (SD %) Range n Mean (SD %) Range n Mean (SD %) Range n Mean (SD %) subjects with no shedding, proportion of subjects with no recurrences, and time to ﬁrst recurrence (Table 2). Valacyclovir 1 g once daily was well tolerated, with similar adverse event reporting compared to placebo. Two subjects withdrew from the study because of adverse events during treatment period 1 and did not progress to treatment period 2. One subject receiving placebo experienced a headache of moderate intensity; a second subject receiving valacyclovir experienced elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) that were felt to be related to a concomitant medication. Both subjects withdrew with- out breaking the study blind and the relationship of the adverse event to the study drug was made while the drug was still blinded. A post-hoc analysis of the 8 subjects with documented incident HSV-2 infection was conducted to explore shedding and recurrence rates in this subset of participants. In an analysis of ﬁrst period placebo treatment data, 4 subjects were HSV-2 seronegative including 3 who were also HSV-1 seronegative (primary infection) and 31 subjects were HSV- 2 seropositive. This analysis suggests that recently infected subjects in the ﬁrst period placebo group shed HSV-2 more often than those already with HSV-2 antibody (Table 3 and Figure 1). In an analysis of ﬁrst period valacyclovir treatment data, 4 subjects were HSV-2 seronegative (including 3 who were also HSV-1 seronegative), and 26 subjects were HSV- 2 seropositive. Among subjects who received valacyclovir in the ﬁrst treatment period, similar results were obtained for Table 3: Post-hoc Analysis of Patients with Documented Incident Infection—Results from the First Treatment Period. Percent days with total shedding, Mean (SD %) P-valueb Percent days with subclinical shedding, Mean (SD %) P-valueb Proportion of subjects recurrence-freec, n (%) HSV-2 Antibody Negativea n = 4 43.8 (18.6 ) P < .001 31.9 (12.8 ) P = .002 0 (0) HSV-2 Antibody Positive n = 31 11.2 (14.8) 8.9 (14.1) 19 (61) a This group includes 3 subjects who were HSV-1 and HSV-2 seronegative, and one subject who was HSV-1 seropositive and HSV-2 seronegative. bThis was an exploratory analysis; P-values should be regarded only as a rough guide to the magnitude of diﬀerences between groups. cThis diﬀerence was statistically signiﬁcant (P = .04); however, this was an exploratory analysis. HSV-2 seronegative and seropositive subjects with respect to total days with shedding (5.9% versus 2.1%) and the proportion of subjects recurrence-free (100% versus 81%). The percentage of days with subclinical shedding was higher in the HSV-2 seronegative group compared to the HSV-2 seropositive (5.9% versus 1.4%, P = .05); however, the study was not powered for this comparison.