Genital Herpes Simplex Virus Infection Research Articles

Neuropsychiatric symptoms and immune activation in patients with genital herpes.

Neuropsychiatric disturbances are common among patients with genital herpes simplex virus (HSV) infection. To date, no studies have examined the possible role of immune activation in the aetiology of these disturbances. The aim of this study was to examine the relationship between markers of immune activation and measures of emotional and somatic dysfunction among patients with symptomatic genital herpes. Twenty-two patients with documented genital herpes were assessed when herpetic lesions were present and when they were not. Each assessment included a clinical examination, self-reported symptom measures as well as a blood and urine collection. Markers of immune activation [neopterin and interleukin (IL)-6] in serum and urine were quantified by enzyme-linked immunoassay. These measures were also obtained from a group of healthy control subjects. Urine, but not serum, levels of neopterin and IL-6 correlated significantly with measures of reported psychological distress and fatigue. These associations were not confined to periods of overt clinical lesions. HSV-related neuropsychiatric morbidity correlates selectively with regional, but not systemic, measures of immune activation. We hypothesise that communication between the local inflammatory site in the pelvis and the brain occurs through autonomic afferent pathways.

Guidelines for the Management of Herpes Simplex Virus in Pregnancy

ObjectiveTo provide recommendations for the management of genital herpes infection in women who want to get pregnant or are pregnant and for the management of genital herpes in pregnancy and strategies to prevent transmission to the infant. OutcomesMore effective management of complications of genital herpes in pregnancy and prevention of transmission of genital herpes from mother to infant. EvidenceMedline was searched for articles published in French or English related to genital herpes and pregnancy. Additional articles were identified through the references of these articles. All study types and recommendation reports were reviewed. ValuesRecommendations were made according to the guidelines developed by the Canadian Task Force on Preventive Health Care. Recommendations1.Women’s history of genital herpes should be evaluated early in pregnancy. (III-A)2.Women with known recurrent genital herpes simplex virus (HSV) should be counselled about the risks of transmission of HSV to their neonates at delivery. (III-A)3.At delivery, women with recurrent HSV should be offered a Caesarean section if there are prodromal symptoms or in the presence of a lesion suggestive of HSV. (II-2A)4.Women with known recurrent genital HSV infection should be offered acyclovir or valacyclovir suppression at 36weeks’ gestation to decrease the risk of clinical lesions and viral shedding at the time of delivery and therefore decrease the need for Caesarean section. (I-A)5.Women with primary genital herpes in the third trimester of pregnancy have a high risk of transmitting HSV to their neonates and should be counselled accordingly and should be offered a Caesarean section to decrease this risk. (II-3B)6.A pregnant woman who does not have a history of HSV but who has had a partner with genital HSV should have type-specific serology testing to determine her risk of acquiring genital HSV in pregnancy before pregnancy or as early in pregnancy as possible. Testing should be repeated at 32 to 34weeks’ gestation. (III-B) ValidationThese guidelines have been reviewed and approved by the Infectious Diseases Committee of the SOGC. SponsorThe Society of Obstetricians and Gynaecologists of Canada

Understanding Herpes Simplex Virus: Transmission, Diagnosis, and Considerations in Pregnancy Management

Genital herpes simplex virus (HSV) infections are frequently asymptomatic or undiagnosed, but more than half the US population is seropositive for HSV, and about one-fifth are positive for HSV-2. These two factors contribute to the risk for sexual transmission and therefore to the risk of late-pregnancy acquisition of HSV. Most neonatal herpes infections are the result of undiagnosed, new-onset HSV infection in the mother. This article reviews the epidemiology of HSV, risks of transmission, and testing and management of HSV during pregnancy. Options for evaluation and management are presented.

The potential impact of a prophylactic herpes simplex vaccine

Background: Herpes simplex virus (HSV) infections have a significant impact on health causing a wide range of diseases. Oral-facial and genital sites are the most common locations of infection and may lead to recurrent painful lesions. HSV infection acquired perinatally may result in severe sequelae or even death despite appropriate therapy. Furthermore, it is becoming increasingly clear that genital HSV infections significantly raise the risk of HIV transmission. Objective: To describe the strategies, impediments, and advancements in the development of vaccines to prevent HSV disease. Methods: A review of the literature was performed, limited to prophylactic HSV vaccines and their potential effect on genital herpes, oral-facial disease, and perinatal herpes. Conclusion: There are several vaccine strategies under development that show promise for the treatment these diseases.

Third trimester antiviral prophylaxis for preventing maternal genital herpes simplex virus (HSV) recurrences and neonatal infection

Genital herpes simplex virus (HSV) infection is one of the most common viral sexually transmitted infections. The majority of women with genital herpes will have a recurrence during pregnancy. Transmission of the virus from mother to fetus typically occurs by direct contact with virus in the genital tract during birth. To assess the effectiveness of antenatal antiviral prophylaxis for recurrent genital herpes on neonatal herpes and maternal recurrences at delivery. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 4), MEDLINE (January 1966 to February 2007) and EMBASE (January 1974 to February 2007; handsearched conference proceedings; reviewed bibliographies of all relevant articles for further references; and contacted experts in the field. Randomized controlled trials which assessed the effectiveness of antivirals compared to placebo or no therapy, on neonatal herpes and maternal disease endpoints among pregnant women with genital herpes. Two authors independently applied study selection criteria and extracted data. Seven randomized controlled trials (1249 participants) which met our inclusion criteria compared acyclovir to placebo or no treatment (five trials) and valacyclovir to placebo (two trials). The effect of antepartum antiviral prophylaxis on neonatal herpes could not be estimated. There were no cases of symptomatic neonatal herpes in the included studies in either the treatment or placebo groups. Women who received antiviral prophylaxis were significantly less likely to have a recurrence of genital herpes at delivery (relative risk (RR) 0.28, 95% confidence interval (CI) 0.18 to 0.43, I(2 )= 0%). Women who received antiviral prophylaxis were also significantly less likely to have a cesarean delivery for genital herpes (RR 0.30, 95% CI 0.20 to 0.45, I(2) = 27.3%). Women who received antiviral prophylaxis were significantly less likely to have HSV detected at delivery (RR 0.14, 95% CI 0.05 to 0.39, I(2) = 0%). 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. The risks, benefits, and alternatives to antenatal prophylaxis should be discussed with women who have a history and prophylaxis initiated for women who desire intervention.

Detection of differences in genomic profiles between herpes simplex virus type 1 isolates sequentially separated from the saliva of the same individual

Background Herpes simplex virus (HSV) is assumed to cause recrudescent lesions, usually through endogenous recurrence and rarely through exogenous re-infection. The occurrence of exogenous re-infection in genital and corneal HSV infections has been previously demonstrated using genomic analysis, while exogenous re-infection in oral-facial HSV infections has not been shown. Objectives To confirm the occurrence of exogenous HSV re-infection in oral-facial HSV infections. Study design Seven isolates (isolates 1–7) of herpes simplex virus type 1 (HSV-1) were sequentially separated from the same individual. Genomic profiles of HSV-1 isolates were studied: (i) by analysis of 20 RFLPs (restriction fragment length polymorphisms) and (ii) by the determination of nucleotide sequences of a PCR-amplified DNA fragment encompassing reiteration VII (hypervariable region) that belongs to sequences containing short tandem repeats. Results Isolates 1–5 were the same (F83 genotype) and isolates 6 and 7 were the same (F84 genotype), although isolates 1–5 were markedly different from isolates 6 and 7 in genomic profiles. Conclusions The infection associated with isolates 6 and 7 was due to exogenous re-infection with F84 genotype virus, thus indicating the occurrence of exogenous HSV re-infection in oral-facial HSV infections.

Factors influencing varicella zoster virus infection after allogeneic peripheral blood stem cell transplantation: low‐dose acyclovir prophylaxis and pre‐transplant diagnosis of lymphoproliferative disorders

Varicella zoster virus (VZV) infection is one of the frequent opportunistic infections after allogeneic bone marrow transplantation, with a high incidence of 30-50%. However, no data have been reported on VZV infection after allogeneic peripheral blood stem cell transplantation (PBSCT). We report a retrospective analysis of VZV infection in 192 allogeneic PBSCT recipients. Twenty-seven patients (14%) received long-term prophylaxis of low-dose acyclovir (200 mg twice daily orally > or =3 months) for recurrent oral (n=21) or genital herpes simplex virus infection (n=5) or for a previous history of recurrent VZV infection (n=1). Forty-two patients (22%) developed VZV infections: localized (n=37) and disseminated infection (n=5). The incidence of VZV infection at 1 and 3 years was 19.3+/-3.3% and 36.8+/-5.2%, respectively. Complications included post-herpetic neuralgia (n=18, 43%), secondary bacterial infections (n=3), and intracranial hemorrhage (n=1) with 2 deaths. A higher risk factor for VZV infection was pre-transplant diagnosis of a lymphoproliferative disorder (LPD): chronic lymphocytic leukemia, Hodgkin's disease, or non-Hodgkin's lymphoma (P=0.021, 52.5% in LPD vs. 32.6% in non-LPD group). The use of low-dose acyclovir prophylaxis (P=0.043, 14.7% in acyclovir vs. 41.6% in nonacyclovir group) was found to be protective. Although no VZV infection episodes were noted during the period of acyclovir prophylaxis, 3 episodes of VZV infection were noted after acyclovir cessation. The incidence of VZV infection after PBSCT was high at 36.8%, with patients transplanted for LPDs at higher risk. The long-term use of low-dose acyclovir may be protective for VZV infection, although it does not completely prevent rebound of late VZV infection.

Stress Studies on Acyclovir

Acyclovir is an antiviral drug of choice in the treatment of many types of herpes virus infections, including genital herpes simplex infections, herpetic conjunctivitis, herpes simplex encephalitis, etc. The present study describes the degradation behavior of acyclovir under different International Conference on Harmonization recommended stress conditions (hydrolysis, oxidation, photolysis, and thermal decomposition) in order to establish a validated stability-indicating high-performance liquid chromatography method. Acyclovir is found to degrade extensively in acidic conditions and oxidative stress. Mild degradation of the drug occurs in alkaline and neutral conditions. The drug is stable to dry heat. The drug is found to be sufficiently stable after light exposure in a solid state; however, photolytic degradation is observed when the drug is exposed as a solution in water. The major degradation product in acidic hydrolysis and photolysis is identified as guanine through comparison with the standard. Separation of drug and the degradation products under various conditions is successfully achieved on a C-18 column utilizing water-methanol in the ratio of 90:10. The flow rate is 1 mL/min, and the detection wavelength is 252 nm. The method is validated with respect to linearity, precision, accuracy, selectivity, specificity, and robustness. The mean values of slope and correlation coefficient are 39.307 and 0.9998 with relative standard deviation values less than 2%. The recovery of the drug is found to be in the range of 97.34% to 102.35%. From the previous study it is concluded that the stability-indicating method developed for acyclovir can be used for analysis of the drug in various stability samples.

Current non-AIDS antiviral chemotherapy

The evolution of antiviral therapy began with developments in the management of influenza and herpes simplex keratitis in the 1960s and early 1970s. However, the field exploded with the successful treatment of herpes simplex encephalitis, herpes zoster and genital herpes simplex virus infections, all occurring in the late 1970s and early 1980s. These advances have contributed to the development of therapies for HIV that have transformed the lives of infected patients in recent years. The clinical fruit of all of these research advances has been an armamentarium of drugs that can be used to successfully treat a variety of viral illnesses. In addition to HIV/AIDS, current antiviral therapy focuses primarily on herpesviruses, hepatitis viruses and influenza. Notably, considerable progress remains to be made in these areas. Moreover, a variety of additional viral diseases currently require the development of specific therapies.

Perineal Herpes Simplex Infection in Bedridden Geriatric Patients

Herpes simplex virus (HSV) lesions are prone to reactivation and recurrence in response to various local or systemic triggering factors. To study the characteristics of five bedridden geriatric patients who presented with herpetic recurrences on the buttocks, gluteal cleft, and perianal region during hospitalization. Data were gathered regarding age, gender, reason for hospitalization, localization of lesions, clinical presentation, previous clinical diagnosis and topical treatments, immune status and immunosuppressant drug intake, as well as prior history of labial or genital herpes. A skin biopsy was taken for histologic examination and immunohistochemical viral identification. Viral culture and viral serology were performed and data regarding antiviral therapy were recorded. The five patients (three women, two men) were aged >80 years and hospitalized for either severe drug-induced renal insufficiency (one case), severe pneumonia (two cases), or stroke causing restricted mobility (two cases). Numerous well demarcated, painful ulcerations developed in the perianal region of these patients, and one patient also presented with some vesicular lesions. The lesions had been confused with mycotic and/or bacterial infections for 10-14 days. No inguinal lymphadenopathies were present and there was no fever. None of the patients had a previous history of recurrent labial or genital HSV infections or HIV infection. Histology was suggestive of HSV infection in two of five patients. Immunohistochemistry identified HSV type I (three patients) and HSV type II (two patients) infections. Viral culture with immunofluorescence viral identification revealed HSV type I in one of the four patients in whom a swab for viral culture was taken. Serology revealed past HSV infection. All lesions cured gradually after 10-14 days of intravenous acyclovir (aciclovir) treatment. Herpetic lesions of the perineal region represent a rare complication in bedridden geriatric patients in the absence of a previous history of HSV infections at the same site. Common traits of patients with this condition were the presence of numerous ulcerated lesions, prolonged time course, and confinement to bed. The latter probably modifies the skin condition, which triggers viral reactivation and favors cutaneous extension of the infection. Complementary diagnostic methods for viral detection and identification are mandatory.

Fever of Unknown Origin in a Migrant Farm Worker from Mexico: History, Her Story and His Story

A 29-year-old migrant farm worker from Mexico presented to a hospital in Ontario with fever of unknown origin. She had arrived in Canada six weeks previously to work at an orchard. Her past medical history included two caesarean sections, postpartum hemorrhage requiring transfusion, and cholecystectomy. She was not on any medications. She began experiencing daily rigors one week after her arrival, often accompanied by drenching sweats, and she lost approximately 5 kg of weight. She had intermittent midthoracic back pain, but no other localizing symptoms. Painful vaginal sores and dysuria developed one week later. She presented to the emergency room, where she was diagnosed with genital herpes simplex and secondary bacterial infection. She was prescribed a one-week course of cephalexin and one dose of azithromycin, but she continued to have rigors. One week later, she developed intermittent epigastric pain with no nausea, vomiting or diarrhea. She returned to the emergency room with a fever of 39.5°C, and was admitted for presumed pelvic inflammatory disease. She was treated with various broad-spectrum antibiotics and acyclovir but remained persistently febrile. All cultures were negative and her pelvic ultrasound was unremarkable. She was transferred to a tertiary care hospital one week later for consultation with an infectious disease specialist. Further questioning revealed that she was from a city in Mexico where she lived in close proximity to chickens. She denied having recent insect bites, sick contacts, intravenous drug use and tattoos. She had two previous male sexual contacts, including her husband, who she said had died at 27 years of age from lung cancer. On examination, she was hemodynamically stable and slightly tachypneic, with a temperature of 38.4°C and an oxygen saturation of 96% on room air. Her head and neck examinations revealed two small umbilicated papules on the right upper eyelid and white lesions on the tongue and buccal mucosa. There was no lymphadenopathy. Her cardiovascular, respiratory, abdominal and neurological examinations were unremarkable. Blood tests on admission were significant for the following: hemoglobin of 90 g/L with a mean corpuscular volume of 75.8 fL, white blood cell count of 3.1×109/L (2.9×109/L neutrophils and 0.2×109/L lymphocytes), aspartate amino-transferase level of 132 U/L, alanine aminotransferase level of 28 U/L, alkaline phosphatase level of 386 U/L, bilirubin level of 6 μmol/L and lactate dehydrogenase level of 1283 U/L. Her chest x-ray showed a diffuse reticulonodular pattern. Diagnostic tests were performed.

Herpes genitalis

Genital herpes simplex virus (HSV-1 and HSV-2) infection is an ulcerative, lifelong, recurring sexually transmitted disease of increasing epidemiologic worldwide importance. Transmission occurs by close skin contact, usually during asymptomatic virus shedding. The virus persists in the dorsal root ganglion where it is not accessible to the host's immune system. The most important risk factor is a person's number of lifetime sex partners. The more extensive first-episode infection is followed by milder recurrences. Recurrence rates differ greatly. The diagnosis is made clinically, microbiologically, and serologically. There are several virostatic agents available for treatment.

Audit of the management of genital herpes simplex infection

We evaluated the management of genital herpes simplex virus (HSV) infection at our clinic. Over six months, 135 patients with primary HSV and 97 patients with recurrent HSV attended. Sixty percent of patients presenting within five days of primary infection were treated with oral acyclovir. Only 53% of patients with primary HSV were given written/verbal information. Follow-up appointments were attended by 78%. Seventy-seven percent of patients with recurrent HSV had at least one viral isolate typed and 72% of patients experiencing episodes exceeding, annually, six were offered suppressive therapy. Our results demonstrate successful management of patients with HSV infections but recommendations are made to reach the standards set by BASSH. Furthermore, we illustrate that improved documentation would go a long way in validating the result.

Genital herpes: antiviral therapy for symptom relief and prevention of transmission

The episodic and daily suppressive treatment of genital herpes is safe and effective with the currently available antiviral agents: acyclovir, valacyclovir and famciclovir. Clinical strategies for the comprehensive management of genital herpes simplex virus infections are recommended. Data from recent clinical trials demonstrating the efficacy of shorter duration of therapy for recurrences and the use of antivirals for the prevention of transmission are reviewed in this article. The factors influencing the choice of therapy, such as cost, ease of dosing and acyclovir resistance are also discussed.

The Spectrum of Genital Herpes Simplex Virus Infection in Men Attending a Sexually Transmitted Disease Clinic

The spectrum of genital herpes (GH) has been understudied in men, especially African American men. Consecutive men attending a sexually transmitted diseases clinic were enrolled in a study of GH epidemiology. Consenting participants answered questionnaires detailing their sexual and social activities and underwent serological testing for herpes simplex virus types 1 and 2 (HSV-1 and -2) and collection of genital swabs for viral detection. Of the 516 men enrolled, 465 (90%) were African American. Antibodies to HSV-1 were present in 315 (61%) of participants, and 233 (45%) had antibodies to HSV-2. Factors associated with HSV-2 infection included older age and African American race. HSV was detected in genital swabs from 52 men; 43 (82.7%) swabs were HSV-2 positive, and 9 (17.3%) were HSV-1 positive. The overall viral shedding rate among men (n = 247) with evidence of GH (HSV-1 or HSV-2 infection) was 21.1%, and the asymptomatic shedding rate in this same group was 5.2%. The sensitivities of culture for detection of HSV-1 and HSV-2 were .22 and .58, respectively, compared with that of polymerase chain reaction. Genital HSV infections are common and largely unrecognized among this segment of the population. HSV-1 infection constitutes a nontrivial proportion of GH in these men.

Diagnostics for Herpes Simplex Virus

Herpes simplex virus (HSV) is one of the most common, yet frequently overlooked, sexually transmitted infections. Since the type of HSV infection affects prognosis and subsequent counseling, type-specific testing to distinguish HSV-1 from HSV-2 is recommended. Although PCR has been the diagnostic standard for HSV infections of the central nervous system, until now viral culture has been the test of choice for HSV genital infection. However, HSV PCR, with its consistently and substantially higher rate of HSV detection, will likely replace viral culture as the gold standard for the diagnosis of genital herpes in people with active mucocutaneous lesions, regardless of anatomic location or viral type. Alternatively, type-specific serologic tests based on glycoprotein G should be the test of choice to establish the diagnosis of HSV infection when no active lesion is present. Given the difficulty in making the clinical diagnosis of HSV, the growing worldwide prevalence of genital herpes and the availability of effective antiviral therapy, there is an increased demand for rapid, accurate laboratory diagnosis of patients with HSV.

Genital Herpes Simplex Virus Infection and Perinatal Transmission of Human Immunodeficiency Virus

To assess the risk of perinatal human immunodeficiency virus (HIV) transmission in HIV-infected women clinically diagnosed with genital herpes simplex virus (HSV) infection during pregnancy. This retrospective analysis included 402 HIV-infected pregnant women who enrolled from 1994-1999 in a multicenter prospective cohort study in New York City, who delivered a liveborn singleton infant with known HIV infection status, and who had information on diagnosis of genital HSV infection during pregnancy. Study participants were determined to have genital HSV infection during pregnancy by documentation of clinical diagnosis. Forty-six (11.4%) of the study participants delivered HIV-infected infants. Twenty-one (5.2%) had clinical diagnosis of genital HSV infection in pregnancy. Six (28.6%) of the 21 HIV-infected women with a clinical diagnosis of genital HSV infection delivered an HIV-infected infant. In univariate analyses, HIV-infected pregnant women with clinical diagnosis of genital HSV infection during pregnancy had a significantly increased risk of perinatal HIV transmission (odds ratio 3.4, 95% confidence interval 1.3-9.3; P = .02). When other factors associated with perinatal HIV transmission were included in a logistic regression model (lack of zidovudine therapy during pregnancy or delivery, prolonged rupture of membranes, and preterm delivery), clinical diagnosis of genital HSV infection during pregnancy remained a significant independent predictor of perinatal HIV transmission (adjusted odds ratio 4.8, 95% confidence interval 1.3-17.0; P = .02). Clinical diagnosis of genital HSV infection during pregnancy in HIV-infected women may be a risk factor for perinatal HIV transmission. If future studies confirm this association, therapy to suppress genital HSV reactivation during pregnancy may be a strategy to reduce perinatal HIV transmission.

Genital herpes

Genital herpes simplex virus (HSV) infections are common. In both developed and developing countries, the incidence of infection appears to be increasing. The epidemiology of HSV is shifting, and new genital infections are increasingly with HSV-1. Such infections are indistinguishable from HSV-2 infections. Acquisition episodes are often asymptomatic and many individuals are unaware of their infection status. Recurrences are more common with HSV-2 genital disease, and almost all carriers will experience a recurrence, posing a potential risk of onward transmission. Acquisition episodes can be severe and complicated. Recurrences may be severe, frequent and associated with a range of complications including psychosexual disturbances. Management requires anticipation of these problems and includes careful patient assessment, timely antiviral therapy, informed counselling and patient education. Many patients fear onward transmission, and clinicians must be aware of the benefits and limitations of the various strategies to manage this risk. Education, counselling, condom promotion and antiviral drugs all appear to have a role. Many epidemiological studies have found close links between the presence of HSV genital infections and increased risk of HIV acquisition and onward transmission. These links are being investigated and may enable development of interventions to manage HIV spread through HSV control.

Genital Herpes Complicating Pregnancy

Approximately 22% of pregnant women are infected with herpes simplex virus (HSV)-2, and 2% of women will acquire HSV during pregnancy. Remarkably, up to 90% of these women are undiagnosed because they are asymptomatic or have subtle symptoms attributed to other vulvovaginal disorders. Diagnosis of genital herpes relies on laboratory confirmation with culture or polymerase chain reaction assay of genital lesions and type-specific glycoprotein G-based serologic testing. Neonatal herpes is the most severe complication of genital HSV infection and is caused by contact with infected genital secretions at the time of labor. Maternal acquisition of HSV in the third trimester of pregnancy carries the highest risk of neonatal transmission. Despite advances in the diagnosis and treatment of neonatal herpes, little change in the incidence or serious sequelae from this infection has occurred. As such, prevention of the initial neonatal infection is critically important. Obstetricians are in a unique position to prevent vertical HSV transmission by identifying women with genital lesions at the time of labor for cesarean delivery, prescribing antiviral suppressive therapy as appropriate, and avoiding unnecessary invasive intrapartum procedures in women with genital herpes. Enhanced prevention strategies include identification of women at risk for HSV acquisition during pregnancy by testing women and possibly their partners for HSV antibodies and providing counseling to prevent transmission to women in late pregnancy.

Acyclovir prophylaxis for pregnant women with a known history of herpes simplex virus: A cost-effectiveness analysis

Previous literature has shown acyclovir to be cost-effective as prophylaxis for women with genital symptomatic herpes simplex virus infection recurrence during pregnancy. We extend this analysis by adding quality-adjusted life year measurements and considering women with a diagnosed history of herpes simplex virus infection but without recurrence in pregnancy. A decision analytic model was designed that compared acyclovir prophylaxis versus no acyclovir for women with a history of diagnosed genital herpes simplex virus infection but without recurrence in pregnancy. Sensitivity analysis and Monte Carlo simulations were performed to test for robustness. We found that 22,286 women must be treated to prevent 1 neonatal death, 8985 women to prevent 1 affected child, and 177 women to prevent 1 cesarean delivery. As compared with no acyclovir, acyclovir prophylaxis at 36 weeks of gestation saves approximately dollar 20 per person and increases total quality-adjusted life years by 0.01. In univariate sensitivity analysis, this result was robust to all reasonable probability and quality-adjusted life year estimates. Monte Carlo simulation demonstrated acyclovir to be cost-effective 100% of the time and cost saving >99% of the time. Acyclovir prophylaxis versus no treatment for pregnant women with a diagnosed history of genital herpes simplex virus infection but without recurrence during pregnancy is cost-effective over a wide range of assumptions.