***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The pharmacokinetics and safety of the L‐valyl ester pro‐drug of acyclovir , valaciclovir ( 256U87 ) , were investigated in two phase I , placebo‐controlled trials in normal volunteers . These included a single‐dose study with doses from 100 to 1000 mg ( single cohort ) and a multiple‐dose investigation with doses from 250 to 2000 mg ( five separate cohorts ) . In each cohort , eight subjects received valaciclovir and four subjects received placebo . Pharmacokinetic findings for valaciclovir and acyclovir were consistent in the two studies . Valaciclovir was rapidly and extensively converted to acyclovir , result ing in significantly greater acyclovir bioavailability ( ~ threefold to fivefold ) compared with that historically observed with high‐dose ( 800 mg ) oral acyclovir . At the higher valaciclovir doses , acyclovir maximum concentration and daily area under the concentration‐time curve approximated those obtained with intravenous acyclovir . The favorable safety profile and enhanced acyclovir bioavailability  from valaciclovir administration has prompted additional clinical evaluations for zoster and herpes simplex virus treatment , as well as cytomegalovirus suppression in immunocompromised patients OBJECTIVE : To determine if suppressive acyclovir near term decreased the frequency of clinical recurrences at delivery in women with recurrent genital herpes simplex virus ( HSV ) infection . METHODS : We conducted a prospect i ve , double-blind , r and omized trial in 234 women with recurrent genital herpes . Women with genital infection of any frequency were enrolled . Patients received either suppressive oral acyclovir 400 mg three times daily or an identical placebo after 36 weeks ' gestation . Clinical lesions were identified , and HSV cultures were obtained at delivery . The frequencies of clinical and sub clinical HSV recurrences at delivery were evaluated . RESULTS : Six percent of patients treated with acyclovir , and 14 % of patients treated with placebo had clinical HSV at delivery ( p = 0.046 ) . No patients in the acyclovir group had positive HSV cultures , compared with 6 % of placebo-treated patients ( p = 0.029 ) . There was no significant difference in sub clinical HSV shedding in the acyclovir group ( 0 % ) compared with the placebo-treated group ( 3 % ) ( p = 0.102 ) . CONCLUSIONS : Suppressive acyclovir therapy significantly decreased the incidence of clinical genital herpes and the overall incidence of HSV excretion at delivery in patients with previous herpes infection We compared the clinical presentation of 95 newborns with herpes simplex virus ( HSV ) infection from 1973 through 1981 ( first period ) with data from 196 newborns evaluated from 1982 through 1987 ( second period ) . There was a significant change in the presentation of infection in these infants . From the first to the second period , the frequency of disseminated disease decreased from 50.5 % to 22.9 % , whereas the frequency of skin , eye , and mouth ( SEM ) diseases increased from 17.9 % to 43.4 % ( P less than .001 ) . The frequency of infants with central nervous system ( CNS ) disease remained relatively unchanged--31.6 % versus 33.7 % . We also compared the demographic and clinical characteristics of the infants and their mothers . For neonates with CNS or disseminated infection , disease duration and frequency of prematurity were significantly decreased in the second period , as was the frequency of skin vesicles for newborns with SEM or disseminated infection . These changes are most likely the consequence of recognizing and treating SEM infection before its progression to more-severe disease A r and omized , double-blind study of valaciclovir for suppression of  recurrent genital herpes  was conducted among 1479 immunocompetent patients . Patients were r and omized to receive valaciclovir ( 250 mg , 500 mg , or 1 g once daily , or 250 mg twice daily ) , acyclovir ( 400 mg twice daily ) , or placebo , for 1 year . All valaciclovir dosages were significantly more effective than placebo at preventing or delaying recurrences ( P < .0001 ) . There was a dose-response relationship ( P < .0001 ) across the once-daily valaciclovir regimens . Twice-daily valaciclovir and acyclovir were similar in effectiveness . Subgroup analysis showed that patients with a history of < 10 recurrences per year were effectively managed with 500 mg of valaciclovir once daily . One gram of valaciclovir once daily , 250 mg of valaciclovir twice daily , or 400 mg of acyclovir twice daily were more effective in patients with > or = 10 recurrences per year . Safety profiles of all treatments were comparable . Thus , valaciclovir is highly effective and well tolerated for suppression of recurrent genital herpes . Once-daily regimens offer a useful option for patients who require suppressive therapy for management of genital herpes Normal adults with six or more episodes of genital herpes in the previous year were enrolled in a one-year , multicenter , double-blind trial comparing placebo with 400 mg of acyclovir administered orally twice daily . Patients with episodes during the study were offered 200 mg of acyclovir administered orally five times daily for five days ; this allowed comparison of suppressive and episodic treatment . After one year , 227 ( 44 % ) of 519 patients receiving suppressive treatment and seven ( 2 % ) of 431 receiving placebo ( episodic ) treatment remained free of recurrences , and the mean numbers of recurrences per year were 1.8 and 11.4 , respectively . Among 67 patients who had received suppressive therapy for one year , the mean duration of lesions in the first episode following the discontinuation of treatment was 9.3 days compared with 7.3 days among 45 patients who had received episodic therapy for one year . Treatment was well tolerated , and no changes were noted in the in vitro susceptibility to acyclovir of herpes simplex virus cultured during or after the one-year trial . Continuous or episodic oral acyclovir therapy for one year remained safe and effective Objective To evaluate the efficacy and safety of a suppressive course of acyclovir in late pregnancy in women with recurrent genital herpes infection on the incidence of viral shedding , herpes lesion development and caesarean section for recurrent genital herpes BACKGROUND Nucleoside analogues against herpes simplex virus ( HSV ) have been shown to suppress shedding of HSV type 2 ( HSV-2 ) on genital mucosal surfaces and may prevent sexual transmission of HSV . METHODS We followed 1484 immunocompetent , heterosexual , monogamous couples : one with clinical ly symptomatic genital HSV-2 and one susceptible to HSV-2 . The partners with HSV-2 infection were r and omly assigned to receive either 500 mg of valacyclovir once daily or placebo for eight months . The susceptible partner was evaluated monthly for clinical signs and symptoms of genital herpes . Source partners were followed for recurrences of genital herpes ; 89 were enrolled in a sub study of HSV-2 mucosal shedding . Both partners were counseled on safer sex and were offered condoms at each visit . The predefined primary end point was the reduction in transmission of symptomatic genital herpes . RESULTS Clinical ly symptomatic HSV-2 infection developed in 4 of 743 susceptible partners who were given valacyclovir , as compared with 16 of 741 who were given placebo ( hazard ratio , 0.25 ; 95 percent confidence interval , 0.08 to 0.75 ; P=0.008 ) . Overall , acquisition of HSV-2 was observed in 14 of the susceptible partners who received valacyclovir ( 1.9 percent ) , as compared with 27 ( 3.6 percent ) who received placebo ( hazard ratio , 0.52 ; 95 percent confidence interval , 0.27 to 0.99 ; P=0.04 ) . HSV DNA was detected in sample s of genital secretions on 2.9 percent of the days among the HSV-2-infected ( source ) partners who received valacyclovir , as compared with 10.8 percent of the days among those who received placebo ( P<0.001 ) . The mean rates of recurrence were 0.11 per month and 0.40 per month , respectively ( P<0.001 ) . CONCLUSIONS Once-daily suppressive therapy with valacyclovir significantly reduces the risk of transmission of genital herpes among heterosexual , HSV-2-discordant couples Objective To determine if suppressive acyclovir therapy given to term gravidas experiencing a first episode of genital herpes simplex virus ( HSV ) infection during pregnancy decreases the need for cesarean delivery for that indication . Methods Forty-six pregnant women with first episodes of genital herpes during pregnancy were r and omly assigned to receive oral acyclovir 400 mg or placebo , three times per day , from 36 weeks ' gestation until delivery as part of a prospect i ve , double-blind trial . Herpes simplex virus cultures were obtained when patients presented for delivery . Vaginal delivery was permitted if no clinical recurrence was present ; otherwise , a cesarean was performed . Neonatal HSV cultures were obtained and infants were followed-up clinical ly . Results None of the 21 patients treated with acyclovir and nine of 25 ( 36 % ) treated with placebo had clinical evidence of recurrent genital herpes at delivery ( odds ratio [ OR ] 0.04 , 95 % confidence interval [ CI ] 0.002 - 0.745 ; P = .002 ) . No woman treated with acyclovir had a cesarean for herpes , compared with nine of 25 ( 36 % ) of those treated with placebo ( OR 0.04 , CI 0.002–0.0745 ; P = .002 ) . No patient in either treatment group experienced asymptomatic genital viral shedding at delivery . No neonate had evidence of herpes infection or adverse effects from acyclovir . Conclusion Suppressive acyclovir therapy reduced the need for cesarean for recurrent herpes in women whose first clinical episode of genital HSV occurred during pregnancy . Suppressive acyclovir treatment did not increase asymptomatic viral shedding and was not harmful to the term fetus OBJECTIVE : To measure the efficacy of valacyclovir suppression in late pregnancy to reduce the incidence of recurrent genital herpes in labor and subsequent cesarean delivery . METHODS : A total of 350 pregnant women with a history of genital herpes were assigned r and omly to oral valacyclovir 500 mg twice a day or an identical placebo from 36 weeks of gestation until delivery . In labor , vulvovaginal herpes simplex virus ( HSV ) culture and polymerase chain reaction ( PCR ) specimens were collected . Vaginal delivery was permitted if no clinical recurrence or prodromal symptoms were present . Neonatal HSV cultures and laboratory tests were obtained , and infants were followed up for 1 month after delivery . Data were analyzed using & khgr;2 and Student t tests . RESULTS : One hundred seventy women treated with valacyclovir and 168 women treated with placebo were evaluated . Eighty-two percent of the women had recurrent genital herpes ; 12 % had first episode , non primary genital herpes ; and 6 % had first episode , primary genital herpes . At delivery , 28 women ( 8 % ) had recurrent genital herpes requiring cesarean delivery : 4 % in the valacyclovir group and 13 % in the placebo group ( P = .009 ) . Herpes simplex virus was detected by culture in 2 % of the valacyclovir group and 24 % of the placebo group ( P = .02 ) . No infants were diagnosed with neonatal HSV , and there were no significant differences in neonatal complications . There were no significant differences in maternal or obstetric complications in either group . CONCLUSION : Valacyclovir suppression after 36 weeks of gestation significantly reduces HSV shedding and recurrent genital herpes requiring cesarean delivery . LEVEL OF EVIDENCE : OBJECTIVE The objective was to obtain preliminary pharmacokinetic data for acyclovir from gravid women receiving herpes simplex virus suppressive therapy with the acyclovir prodrug valacyclovir .  STUDY DESIGN In a prospect i ve , double-blind trial , 20 women with a history of recurrent genital herpes simplex virus infection and positive herpes simplex virus 2 serologic results were r and omly assigned at 36 weeks ' gestation to receive oral valacyclovir ( 500 mg twice daily ) or acyclovir ( 400 mg 3 times daily ) .  Acyclovir pharmacokinetic profiles were obtained after the initial dose ( 36 weeks ) and at steady state ( 38 weeks ) . Amniotic fluid sample s were obtained during labor and simultaneous umbilical cord and maternal plasma sample s were collected at delivery . Laboratory studies were performed to screen for laboratory evidence of toxicity in mothers and infants . RESULTS Peak acyclovir plasma concentrations ( mean + /- st and ard deviation ) were higher in valacyclovir recipients than in acyclovir recipients after the initial dose ( 3.14 + /- 0.7 microg 
    Output:
    
Women with recurrent genital herpes simplex virus should be informed that the risk of neonatal herpes is low .
There is insufficient evidence to determine if antiviral prophylaxis reduces the incidence of neonatal herpes .
Antenatal antiviral prophylaxis reduces viral shedding and recurrences at delivery and reduces the need for cesarean delivery for genital herpes .
Limited information exists regarding the neonatal safety of prophylaxis .