Recurrent Genital Herpes Simplex Research Articles

Pharmacokinetics of oral valacyclovir and acyclovir in late pregnancy

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 prospective, double-blind trial, 20 women with a history of recurrent genital herpes simplex virus infection and positive herpes simplex virus 2 serologic results were randomly 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 samples were obtained during labor and simultaneous umbilical cord and maternal plasma samples 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 ± standard deviation) were higher in valacyclovir recipients than in acyclovir recipients after the initial dose (3.14 ± 0.7 μg/mL vs 0.74 ± 0.6 μg/mL, P < .0001) and at steady state (3.03 ± 1.0 μg/mL vs 0.94 ± 0.7 μg/mL, P < .001). The daily area under the curve values were higher in valacyclovir recipients than acyclovir recipients after the initial dose (17.8 ± 3.6 h · μg/mLvs 7.71 ± 2.5 h · μg/mL, P < .001) and at steady state (19.65 ± 6.4 h · μg/mL versus 11.0 ± 4.5 h · μg/mL, P = .009). There was no significant difference in drug elimination half-life or in time to peak concentration between valacyclovir and acyclovir recipients at either sampling interval. Acyclovir was concentrated in the amniotic fluid; however, there was no evidence of preferential fetal drug accumulation (mean maternal/umbilical vein plasma ratios at delivery were 1.7 for valacyclovir and 1.3 for acyclovir). Valacyclovir was well tolerated, and no significant laboratory or clinical evidence of toxicity was detected. Conclusion: In this phase I trial maternal valacyclovir therapy resulted in higher plasma acyclovir levels, with significantly higher peak concentrations and daily area under the curve values, than did acyclovir therapy. Additional trials are needed to further evaluate the safety and efficacy of suppressive valacyclovir therapy during late pregnancy. (Am J Obstet Gynecol 1998;179:846-51.)

The relationship between psychological factors and recurrent genital herpes simplex virus

Purpose. This paper reviews the relationship between psychological factors and recurrent genital herpes simplex virus (HSV).Method. Studies for the review were selected via computerized literature searches and were included if they specifically examined the relationship between genital HSV recurrence and psychological factors. Twenty‐nine studies addressing this relationship are evaluated and discussed.Findings. Factors reported to be associated with recurrences include depression, stress, coping strategies, social support and illness vulnerability. However, findings are inconsistent due to variations in study design.Conclusions. In general, the literature suggests that exposure to psychological stressors alone is not sufficient to trigger HSV recurrence. Although a correlation between psychological factors and number of recurrences exists, it may be that recurrences cause greater stress and depression, or that a third factor puts people at greater risk of both stress and recurrences. Personality traits, coping mechanisms and interpersonal factors, also determine the extent of the impact of the stressor on the individual. Further studies are needed to address these factors and control for the variations in designs found in the current literature.

Do Antepartum Herpes Simplex Virus Cultures Predict Intrapartum Shedding for Pregnant Women With Recurrent Disease?

Objective: To examine antenatal screening as a predictor of intrapartum shedding of herpes simplex virus (HSV) and to determine its usefulness in guiding the appropriate route of delivery for patients with recurrent HSV in pregnancy.Methods: A population of 198 pregnant women with a history of recurrent genital HSV were cultured in the last weeks of their pregnancy by specially‐trained personnel and intrapartum by their delivering attendants.Results: Of cultures from a total of 906 antenatal visits, 17% were culture positive, with an asymptomatic shedding rate of 3.4%. Asymptomatic shedding occurred in 12.6% of women. Over the 8‐week antepartum period, viral culture‐positivity rates for each visit ranged from 11% to 19.5%. This provided an expected delivery culture‐positivity rate of 15.3%. However, actual intrapartum viral culture positivity occurred in only three of 191 women (1.5%; P &lt; 0.001). Because previous studies have suggested antepartum culture positivity fails to predict intrapartum viral shedding, evaluations, including cultures, as well as predictive values for subsequent culture positivities, were determined under the supervision of an infectious disease specialist. Under these conditions, positive predictive values were 59% when the interval between visits was 2 days, but only 19% when days between visits were &gt;2 (P &lt; 0.0001). No cases of neonatal herpes were seen in this population, although cesarean deliveries were performed in 31% of the patient population, with genital herpes as the indication for 56% of those.Conclusions: Antepartum serial screening by viral culture is not predictive of an infant′s risk of intrapartum viral exposure when conducted at weekly intervals. However, more frequent assessments of patients can be predictive of an infant′s exposure risk to HSV; for patients with frequent recurrent disease near term or primary infection in pregnancy, frequent late antepartum screening may be appropriate. Infect. Dis. Obstet. Gynecol. 7:230–236, 1999.

Suppression of recurrent genital herpes simplex virus type 2 infection by Rhus javanica in guinea pigs

Rhus javanica has been shown to exhibit anti-herpes simplex virus (HSV) activity and potentiate the anti-HSV activity of acyclovir in vitro and in vivo. This extract was examined for its suppressive efficacy on recurrent genital infection in guinea pigs. Guinea pigs were primarily infected intravaginally with HSV type 2 (HSV-2). Prophylactic oral administration, at the dose corresponding to human use, of R. javanica significantly reduced the incidence, severity and/or frequency of spontaneous and severe skin lesions as compared with latently infected guinea pigs administered with water. This prophylactic efficacy was confirmed by the crossover administration, for more than 2 months, of R. javanica and water to the infected guinea pigs. Toxicity, such as weight loss, from R. javanica administration was not observed in the guinea pigs. When recurrent HSV-2 disease was induced by ultraviolet irradiation 3 months after primary infection, the prophylaxis with R. javanica was also significantly effective in reducing the severity of ultraviolet-induced skin lesions. Thus, prophylaxis of recurrent genital HSV-2 infection with R. javanica may preserve the efficacy of acyclovir by reducing both the use of acyclovir and the appearance of acyclovir-resistant viruses.

Are reported stress and coping style associated with frequent recurrence of genital herpes?

OBJECTIVES: This paper reports on the cross sectional data from the longitudinal study examining the impact of genital herpes simplex virus (HSV) infection on quality of life. In particular the...

Valaciclovir for the suppression of recurrent genital HSV infection: a placebo controlled study of once daily therapy. International Valaciclovir HSV Study Group.

OBJECTIVE: To determine the efficacy and safety of once daily valaciclovir for the suppression of recurrent genital herpes simplex virus (HSV) infection in immunocompetent patients. METHODS: 382 otherwise healthy patients...

Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: a randomised, double blind clinical trial. International Valaciclovir HSV Study Group.

OBJECTIVE: To compare the efficacy and safety of twice daily valaciclovir with five times daily aciclovir in the treatment of an episode of recurrent genital herpes simplex virus (HSV) infection...

HIV Infection in Women

To further characterize the natural history of HIV infection in women in the antiretroviral era, we performed a longitudinal, descriptive analysis of demographic features, clinical characteristics, patterns of antiretroviral and prophylactic therapy, disease progression, and survival in a cohort of women followed at a university medical center from 1986 to 1992. Eighty-two women (39 white [non-Hispanic], 33 African-American, 10 Hispanic) were followed for a median of 13 months (range 3-61 months). Sixty-two women received antiretroviral therapy, 34 through participation in a clinical trial. Candida esophagitis and Pneumocystis carinii pneumonia were the most common AIDS-defining conditions, accounting for 77% of all initial AIDS-defining diagnoses. Gynecologic complications affected 34 women (41%) and included recurrent Candida vaginitis in 26, abnormal PAP smears/cervical intraepithelial neoplasia in 10, and recurrent genital herpes simplex virus disease in seven. Median survival (Kaplan-Meier) from the time of HIV serodiagnosis was > 59 months; median survival following an AIDS diagnosis was 27 months. No survival differences were detected based on race, insurance status, or mode of HIV transmission. Women who participated in antiretroviral therapy clinical trials had a statistically significantly longer duration of survival compared with nonparticipants. Candida infections and gynecologic diseases were common in this population. Overall survival was similar to that reported for men.

Effect of imiquimod as an adjuvant for immunotherapy of genital HSV in guinea-pigs

Imiquimod, an immunomodulator which upregulates cell-mediated immune responses, was evaluated as an adjuvant for immunotherapy of recurrent genital herpes simplex virus (HSV) infection in guinea-pigs. In two experiments at separate research centres, animals were immunized with HSV glycoprotein and either placebo, 1 or 5 days of imiquimod, or complete Freund's adjuvant, 14 and 35 days after genital HSV-2 infection. Recurrent lesion days were then evaluated from days 15–91. In both experiments, immunization with glycoprotein and imiquimod most effectively reduced recurrence compared with unimmunized controls (53–69%, p<0.001−0.05). A peak reduction of 70–80% was observed following the second immunization. This reduction was greater than that provided by immunization with glycoprotein and complete Freund's adjuvant in these experiments or those previously reported.

Antigenic specificities of human CD4+ T-cell clones recovered from recurrent genital herpes simplex virus type 2 lesions.

Lesions resulting from recurrent genital herpes simplex virus (HSV) infection are characterized by infiltration of CD4+ lymphocytes. We have investigated the antigenic specificity of 47 HSV-specific CD4+ T-cell clones recovered from the HSV-2 buttock and thigh lesions of five patients. Clones with proliferative responses to recombinant truncated glycoprotein B (gB) or gD of HSV-2 or purified natural gC of HSV-2 comprised a minority of the total number of HSV-specific clones isolated from lesions. The gC2- and gD2-specific CD4+ clones had cytotoxic activity. The approximate locations of the HSV-2 genes encoding HSV-2 type-specific CD4+ antigens have been determined by using HSV-1 x HSV-2 intertypic recombinant virus and include the approximate map regions 0.30 to 0.46, 0.59 to 0.67, 0.67 to 0.73, and 0.82 to 1.0 units. The antigenic specificity of an HLA DQ2-restricted, HSV-2 type-specific T-cell clone was mapped to amino acids 425 to 444 of VP16 of HSV-2 by sequential use of an intertypic recombinant virus containing VP16 of HSV-2 in an HSV-1 background, recombinant VP16 fusion proteins, and synthetic peptides. Each of the remaining four patients also yielded at least one type-specific T-cell clone reactive with an HSV-2 epitope mapping to approximately 0.67 to 0.73 map units. The antigenic specificities of lesion-derived CD4+ T-cell clones are quite diverse and include at least 10 epitopes. Human T-cell clones reactive with gC and VP16 are reported here for the first time.

Risk factors for the sexual transmission of genital herpes.

To determine the risk of sexual transmission of genital herpes simplex virus (HSV) in heterosexual couples. Prospective study of couples who were participants in a clinical trial. Each source partner had symptomatic, recurrent genital HSV, and each susceptible partner was without serologic or clinical evidence of genital herpes. Couples were followed for a median of 334 days. Two university-based research clinics. One hundred forty-four heterosexual couples were studied out of an initial enrollment of 214 couples. Development of culture-proven HSV infection or type-specific antibodies in the susceptible partner. Transmission occurred in 14 (9.7%) couples, including 11 (16.9%) of 65 couples with male and 3 (3.8%) of 79 with female source partners (P = 0.05). The annual rate of acquisition was higher (31.8%) in susceptible female partners who lacked antibodies to either HSV type 1 or 2 at entry compared with females with HSV type 1 antibodies at entry (9.1%). Couples avoiding transmission of HSV reported fewer days with genital lesions in source partners. Detailed histories were available at the time of transmission in 13 couples. In nine couples, transmission occurred when the source partner was reported to be asymptomatic and in four, it resulted from sexual contact at the time of prodrome (1 case) or within hours before lesions were first noticed by the source partner (3 cases). Despite clear recognition of genital herpes in source partners, there was substantial risk for transmission; in 70% of patients, transmission appeared to result from sexual contact during periods of asymptomatic viral shedding. The risk for acquisition of HSV was higher in women than men, and previous HSV type 1 infection appeared to reduce the risk for acquisition of HSV type 2 infection among women.

Capsaicin Interferes with the Centrifugal Spread of Virus in Primary and Recurrent Genital Herpes Simplex Virus Infections

The neural spread of herpes simplex virus (HSV) via sensory nerves is an essential component of disease pathogenesis. Capsaicin, a specific toxin for sensory C-type fibers, interferes with neuronal function including axonal transport. Capsaicin treatment of guinea pigs before intravaginal HSV inoculation did not prevent ganglionic infection but ameliorated cutaneous herpetic disease, suggesting that anterograde but not retrograde virus spread involved a capsaicin-sensitive process. Similarly, treatment of latently infected animals reduced both spontaneous and ultraviolet radiation-induced herpetic recurrences, suggesting that capsaicin interfered with the anterograde spread of reactivated virus. These results suggest that the centrifugal spread of virus may involve either different pathways or mechanisms than are involved in centripetal HSV spread. The use of selective neuropharmacologic agents such as capsaicin may prove useful in further defining the pathophysiology of HSV disease.

Frequency of Asymptomatic Shedding of Herpes Simplex Virus in Women with Genital Herpes

Twenty-seven women with recurrent genital herpes simplex virus infection underwent daily home culturing to detect asymptomatic genital herpes simplex virus shedding. Asymptomatic herpes simplex virus shedding was documented on 1% of the days on which cultures were obtained. Asymptomatic shedding from the vulva was as frequent as asymptomatic cervicovaginal shedding, and 45% of asymptomatic episodes were identified only by positive results from vulvar cultures. All women who obtained samples on more than 100 days and 80% of women who obtained samples on more than 50 days had documented asymptomatic viral shedding, compared with only 6% of those who obtained samples for fewer than 25 days. Asymptomatic shedding was not related to contraceptive use or menstrual cycle. These data suggest that all women with recurrent genital herpes simplex virus infection should be instructed about the possible risk, albeit infrequent, of asymptomatically shedding virus from the genital tract.

Asymptomatic Herpes Simplex Virus Shedding from the Genital Tract Whilst on Suppressive Doses of Oral Acyclovir

Forty-eight patients were recruited into a study of continuous oral acyclovir therapy for the suppression of recurrent genital herpes simplex virus (HSV) infection. Seven of these patients were shown to shed HSV in the absence of clinical signs or symptoms whilst on medication. The asymptomatic shedders did not differ significantly from the rest of the group in terms of age, interval from first attack to enrollment or number of recurrences prior to enrollment. Only one patient admitted to poor compliance as a trigger to asymptomatic HSV shedding. Failure to suppress asymptomatic shedding during prophylactic acyclovir therapy may have implications for sexual transmission to partners and vertical transmission to neonates and requires further study.

Frequency of Asymptomatic Shedding of Herpes Simplex Virus in Women With Genital Herpes

Twenty-seven women with recurrent genital herpes simplex virus infection underwent daily home culturing to detect asymptomatic genital herpes simplex virus shedding. Asymptomatic herpes simplex virus shedding was documented on 1% of the days on which cultures were obtained. Asymptomatic shedding from the vulva was as frequent as asymptomatic cervicovaginal shedding, and 45% of asymptomatic episodes were identified only by positive results from vulvar cultures. All women who obtained samples on more than 100 days and 80% of women who obtained samples on more than 50 days had documented asymptomatic viral shedding, compared with only 6% of those who obtained samples for fewer than 25 days. Asymptomatic shedding was not related to contraceptive use or menstrual cycle. These data suggest that all women with recurrent genital herpes simplex virus infection should be instructed about the possible risk, albeit infrequent, of asymptomatically shedding virus from the genital tract.

Topical Alpha-Interferon in Recurrent Genital Herpes Simplex Infection

We conducted a double-blind placebo-controlled clinical trial on 98 subjects to assess the efficacy of two strengths of topical human leukocyte alpha-interferon, 10(4) and 10(6) IU/g in a 1% nonoxynol-9 base, in the treatment of recurrent genital herpes simplex virus (HSV). The study medication was applied during the prodromal phase or at the first sign of recurrence of the infection. The high-dose alpha-interferon was found to be significantly more effective than the low-dose interferon and placebo with respect to the duration of viral shedding as well as in reducing the time to the end of all subjective symptoms, including pain, burning and itching. No difference between the three groups was found in times to crusting or healing. Further studies of topical interferon in the treatment of HSV and other viral infections are merited.

Characteristics of recurrent genital herpes simplex infections in pregnant women

Longitudinal study of 229 pregnancies in 186 pregnant women with recurrent genital herpes simplex virus (HSV) infections revealed an increased incidence of recurrent episodes in the third trimester compared with the first or second trimesters. The duration of symptomatic recurrences did not change with each trimester. Cervical HSV shedding concomitant with HSV culture-positive vulvar lesions did not change significantly with advancing gestation. The presence of an HSV culture-positive vulvar lesion indicated a significantly (P less than .001) greater risk of concomitant cervical HSV shedding (44 of 333, 13.2%) than in pregnant women with HSV culture-positive remote lesions (zero of 60) or in asymptomatic women (27 of 1460, 1.9%). Comparison of the characteristics among 43 pairs of pregnancies in 34 women revealed no consistent change over time. This study of the natural history of genital HSV recurrences in pregnant women demonstrated no proclivity for an increased rate of preterm delivery (1.3%) or congenital anomalies (2.2%) in a predominantly white, non-Hispanic middle-class population.

Animal model of ultraviolet‐radiation‐induced recurrent herpes simplex virus infection

The development of a model of induced recurrent herpes simplex virus disease would facilitate studies of the mechanism(s) responsible for reactivation of latent virus. The guinea pig model of genital herpes is characterized by a self-limited primary infection, the establishment of a latent infection in sensory ganglia, and the subsequent development of spontaneous recurrent genital infections. This study reports that exposure of latently infected female guinea pigs to ultraviolet radiation results in the induction of recurrent genital herpes simplex virus infections in approximately 60% of animals. Furthermore, there was a dose-response relationship between ultraviolet irradiation and ability to induce recurrent disease. This model should prove useful in further investigations of the pathophysiology of herpes simplex infections.

Non-specific active immunotherapy in patients with recurrent genital herpes simplex virus (HSV) infections

Non-specific active immunotherapy in patients with recurrent genital herpes simplex virus (HSV) infections

Recurrent genital herpes: what helps adjustment?

Psychosocial adjustment to recurrent genital infections with herpes simplex virus (HSV) varies greatly among individuals. To identify the factors predictive of psychosocial adjustment to recurrent genital HSV infections, we analyzed data from interviews and psychological tests conducted with infected individuals. We found that avoidant coping strategies such as denial and social support from a counselor were negatively correlated with adjustment to genital HSV, whereas cognitive coping strategies and social support from one's spouse or lover were positively correlated with adjustment. We conclude that psychosocial adjustment to recurrent genital HSV infections might be facilitated by sharing one's diagnosis with supportive intimate others and avoiding denial as a defense mechanism.