Abstract
Sera from patients with first episode primary genital herpes infections who were treated with the antiviral drug acyclovir were studied to determine the effect of therapy on the immune response to herpes simplex virus (HSV) glycoproteins and polypeptides. 63 patients were evaluated, 35 patients received acyclovir: 11 intravenously, 12 orally, and 12 topically, while 28 received placebo. Topical application of acyclovir had no effect on the immune response to HSV infection. However, both oral and intravenous acyclovir were associated with later development of antibodies to two glycoproteins (of 80,000 and 60,000 mol wt [IIg80 and gD, respectively]) and one nonglycosylated polypeptide of 66,000 mol wt (vp66). Antibody to IIg80 was present in convalescent phase serum in 13/23 systemic acyclovir recipients vs. 18/19 placebo recipients (P = 0.01) and antibody to gD was detected in 8/23 oral or intravenous acyclovir recipients vs. 11/19 placebo recipients (P = 0.06). The mean time to seroconversion to IIg80 (39.0 d) and gD (55.5 d) was significantly longer for systemic acyclovir recipients than for the placebo controls, 23.4 and 18.5 d, respectively (P less than 0.05 for each comparison). 7 (30%) of 23 systemic acyclovir recipients compared with 100% of the placebo recipients had antibody to vp66 by 30 d after onset of the primary episode (P less than 0.001). Subsequent untreated recurrences of genital herpes were associated with seroconversion to gD, IIg80, and vp66. Patients who lacked antibody to both gD and vp66 in sera taken before their first clinical recurrence of disease experienced a longer duration of the recurrent episode (10.8 d) than those who possessed antibody to both vp66 and gD (6.3 d) (P less than 0.05). In addition, the mean duration of lesions, number of lesions, and mean lesion area were greater in patients who lacked antibody to vp66 but had anti gD, as compared with those who had anti-p66 but lacked anti-gD; suggesting that antibody to vp66 correlated more closely with subsequent disease severity than did antibody to gD. Acyclovir therapy appears to influence the frequency and time of development of antibody to a number of different HSV-specific polypeptides. Further studies of the effects of antiviral therapies on the immune response to these proteins may help clarify the role of these polypeptides in the pathogenesis of disease.
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