Genital Herpes Lesions Research Articles

Investigating the survival of herpes simplex virus on toothbrushes and surrogate phallic devices.

Herpes simplex virus-1 (HSV-1) is a member of the alphaherpesvirus (alphaherpesvirinae) subfamily, allowing it to affect a wide range of hosts. Herpes simplex virus-1 affects 3.7 billion people, or 67% of the population, under the age of 50. With a vast number of people infected by the virus, everyday objects are often contaminated with this agent. In this study we determined how long HSV-1 can remain viable on contaminated fomites. Fomites were selected for their use near potentially contaminated orifices and variable frequency of sanitization. Toothbrushes and surrogate phallic devices (SPDs) were cut, sterilized, and contaminated. After contaminating the fomites, we collected samples over a 24h period, then used plaque assays to determine viral titers at prescribed time points. The quantity of replication-competent virus present appears to decrease significantly 2h post-contamination, then steadily declines over time, nearing zero at 24h. Our findings suggest that different surfaces influence HSV-1 survival. Proper cleaning must be performed for these types of fomites, especially if shared in an environment where someone with active genital or oral herpes lesions uses one of these fomites shortly after someone else.

AAP Publications Retired

Clinical report. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. [Retired March 2022] Pediatrics. 2013;131(2):e635–e646.Clinical report. Recognizing and responding to medical neglect. [Retired March 2022] Pediatrics. 2007;120(6):1385–1389.

Congenital Infections: Priorities and Possibilities for Resource-limited Settings.

Congenital Infections: Priorities and Possibilities for Resource-limited Settings.

Immunological Identification and Characterization of the Capsid Scaffold Protein Encoded by UL26.5 of Herpes Simplex Virus Type 2.

Herpes simplex virus type 2 (HSV2), a pathogen that causes genital herpes lesions, interferes with the host immune system via various known and unknown mechanisms. This virus has been used to study viral antigenic composition. Convalescent serum from HSV2-infected patients was used to identify viral antigens via 2-D protein electrophoresis and immunoblotting. The serum predominantly recognized several capsid scaffold proteins encoded by gene UL26.5, mainly ICP35. This protein has been primarily reported to function temporarily in viral assembly but is not expressed in mature virus particles. Further immunological studies suggested that this protein elicits specific antibody and cytotoxic T lymphocyte (CTL) responses in mice, but these responses do not result in a clinical protective effect in response to HSV2 challenge. The data suggested that immunodominance of ICP35 might be used to design an integrated antigen with other viral glycoproteins.

B cells join T cell clusters in the host response to recurrent herpes simplex virus 2 infection.

Recurrent genital herpes lesions are infiltrated by various leukocytes, yet the role of B cell subsets in this process is unknown. In this issue of the JCI, Ford et al. describe the presence and antibody-secreting role of local B cell populations in herpes simplex virus 2 (HSV-2) recurrent lesions. The authors analyzed a comprehensive array of sequential skin biopsy specimens from HSV-2-infected patients over time and at various stages of infection. Using immunofluorescence and in situ hybridization, the authors show the presence of rare IgD+ naive B cells and IgG-expressing antibody-secreting cells (ASCs) in recurrent HSV-2 lesions embedded in CD4+ T cell-rich dermal immune infiltrates, levels of which transiently increase during lesion reactivation and healing. Notably, local increases in HSV-2-specific antibodies in recurrent lesions were detected, whereas serum HSV-2 antibody levels remained stable. Future research is needed to understand the precise role of these tissue-visiting B cells in disease resolution.

Therapeutic Mucosal Vaccination of Herpes Simplex Virus 2-Infected Guinea Pigs with Ribonucleotide Reductase 2 (RR2) Protein Boosts Antiviral Neutralizing Antibodies and Local Tissue-Resident CD4+ and CD8+ TRM Cells Associated with Protection against Recurrent Genital Herpes.

Reactivation of herpes simplex virus 2 (HSV-2) from latency causes viral shedding that develops into recurrent genital lesions. The immune mechanisms of protection against recurrent genital herpes remain to be fully elucidated. In this preclinical study, we investigated the protective therapeutic efficacy, in the guinea pig model of recurrent genital herpes, of subunit vaccine candidates that were based on eight recombinantly expressed HSV-2 envelope and tegument proteins. These viral protein antigens (Ags) were rationally selected for their ability to recall strong CD4+ and CD8+ T-cell responses from naturally "protected" asymptomatic individuals, who, despite being infected, never develop any recurrent herpetic disease. Out of the eight HSV-2 proteins, the envelope glycoprotein D (gD), the tegument protein VP22 (encoded by the UL49 gene), and ribonucleotide reductase subunit 2 protein (RR2; encoded by the UL40 gene) produced significant protection against recurrent genital herpes. The RR2 protein, delivered either intramuscularly or intravaginally with CpG and alum adjuvants, (i) boosted the highest neutralizing antibodies, which appear to cross-react with both gB and gD, and (ii) enhanced the numbers of functional gamma interferon (IFN-γ)-producing CRTAM+ CFSE+ CD4+ and CRTAM+ CFSE+ CD8+ TRM cells, which express low levels of PD-1 and TIM-3 exhaustion markers and were localized to healed sites of the vaginal mucocutaneous (VM) tissues. The strong B- and T-cell immunogenicity of the RR2 protein was associated with a significant decrease in virus shedding and a reduction in both the severity and frequency of recurrent genital herpes lesions. In vivo depletion of either CD4+ or CD8+ T cells significantly abrogated the protection. Taken together, these preclinical results provide new insights into the immune mechanisms of protection against recurrent genital herpes and promote the tegument RR2 protein as a viable candidate Ag to be incorporated in future genital herpes therapeutic mucosal vaccines.IMPORTANCE Recurrent genital herpes is one of the most common sexually transmitted diseases, with a global prevalence of HSV-2 infection predicted to be over 536 million worldwide. Despite the availability of many intervention strategies, such as sexual behavior education, barrier methods, and the costly antiviral drug treatments, eliminating or at least reducing recurrent genital herpes remains a challenge. Currently, no FDA-approved therapeutic vaccines are available. In this preclinical study, we investigated the immunogenicity and protective efficacy, in the guinea pig model of recurrent genital herpes, of subunit vaccine candidates that were based on eight recombinantly expressed herpes envelope and tegument proteins. We discovered that similar to the dl5-29 vaccine, based on a replication-defective HSV-2 mutant virus, which has been recently tested in clinical trials, the RR2 protein-based subunit vaccine elicited a significant reduction in virus shedding and a decrease in both the severity and frequency of recurrent genital herpes sores. This protection correlated with an increase in numbers of functional tissue-resident IFN-γ+ CRTAM+ CFSE+ CD4+ and IFN-γ+ CRTAM+ CFSE+ CD8+ TRM cells that infiltrate healed sites of the vaginal tissues. Our study sheds new light on the role of TRM cells in protection against recurrent genital herpes and promotes the RR2-based subunit therapeutic vaccine to be tested in the clinic.

The Effect of Hormonal Contraception and Menstrual Cycle Timing on Genital Herpes Simplex Virus-2 Shedding and Lesions.

The effect of female sex hormones on herpes simplex virus (HSV)-2 shedding and lesion frequency is poorly understood. Previous studies suggest that hormonal contraception may increase the frequency of HSV-2 shedding. We studied HSV-2 seropositive women who performed daily genital swabbing for HSV DNA and completed diaries for genital lesions and menses. We used Poisson mixed effects models to determine if HSV detection varied throughout the menstrual cycle, or in response to hormonal contraception. We used the Wilcoxon signed-rank test and rank-sum test to determine if lesion frequency differed by cycle phase or hormonal contraceptive use. In 189 women aged 19 to 46 years who collected swabs on 10,715 days and were not using hormonal contraception, HSV-2 DNA was detected on 20.9% of days in the follicular phase and 17.8% of days in the luteal phase (rate ratio, 1.19; 95% confidence interval, 1.03-1.37, P = 0.02). Genital lesions did not differ in the follicular versus luteal phase (12.8% vs. 10.7%, P = 0.07). In analyses of hormonal contraception, including 244 women, HSV-2 DNA was detected on 19.0% of days for women not using hormonal contraception and 18.3% of days for those using hormonal contraception (P = 0.50). Lesions were present on 11.1% of days for women not using hormonal contraception, and 8.7% of days for those using hormonal contraception (P = 0.66). In women with genital HSV-2 infection who are not using hormonal contraception, the follicular phase of the cycle may be associated with a higher frequency of HSV-2 shedding compared to the luteal phase. Lesion frequency is similar during the 2 menstrual phases. Hormonal contraception use was not observed to affect genital HSV-2 DNA detection or lesions.

Herpes Simplex Virus Shedding Rate: Surrogate Outcome for Genital Herpes Recurrence Frequency and Lesion Rates, and Phase 2 Clinical Trials End Point for Evaluating Efficacy of Antivirals.

We tested whether genital herpes simplex virus (HSV) shedding is an appropriate surrogate outcome for the clinical outcome of genital herpes lesions in studies of HSV-2 antiviral interventions. We analyzed prospective data from natural history studies and clinical trials of antiviral agents for HSV-2 in which HSV-2-seropositive participants provided self-collected anogenital swab specimens daily over ≥25 days for HSV DNA quantitation by polymerase chain reaction (PCR). Genital recurrences were self-reported. Among 674 participants, genital HSV shedding was detected on 17% of days, and genital lesions were reported on 10% of days. Within the same session, HSV shedding rates were strongly correlated with lesion rates (ρ = 0.61, P < .0001). The relative reduction in the recurrence rate was 72% (P = .041) for recipients of the antiviral agent pritelivir as compared to recipients of placebo, but it decreased to 21% (P = .75) after adjustment for HSV shedding rate. When evaluating valacyclovir and acyclovir, adjustment for the HSV shedding rate also led to a reduced association of these antivirals with the recurrence rate. Overall, 40%-82% of the antiviral effect on recurrences was explained by its effect on HSV shedding. HSV genital shedding measured by PCR analysis in swab specimens self-collected daily is an appropriate surrogate outcome for genital herpes lesions because it is in the causal pathway to recurrences.

The effect of hormonal contraception and menstrual cycle timing on genital herpes simplex virus-2 shedding and lesions

Background The effect of female sex hormones on herpes simplex virus (HSV)-2 shedding and lesion frequency is poorly understood. Previous studies suggest that hormonal contraception may increase the frequency of HSV-2 shedding. Methods We studied HSV-2 seropositive women who performed daily genital swabbing for HSV DNA and completed diaries for genital lesions and menses. We used Poisson mixed effects models to determine if HSV detection varied throughout the menstrual cycle, or in response to hormonal contraception. We used the Wilcoxon signed-rank test and rank-sum test to determine if lesion frequency differed by cycle phase or hormonal contraceptive use. Results In 189 women aged 19 to 46 years who collected swabs on 10,715 days and were not using hormonal contraception, HSV-2 DNA was detected on 20.9% of days in the follicular phase and 17.8% of days in the luteal phase (rate ratio, 1.19; 95% confidence interval, 1.03-1.37, P = 0.02). Genital lesions did not differ in the follicular versus luteal phase (12.8% vs. 10.7%, P = 0.07). In analyses of hormonal contraception, including 244 women, HSV-2 DNA was detected on 19.0% of days for women not using hormonal contraception and 18.3% of days for those using hormonal contraception (P = 0.50). Lesions were present on 11.1% of days for women not using hormonal contraception, and 8.7% of days for those using hormonal contraception (P = 0.66). Conclusions In women with genital HSV-2 infection who are not using hormonal contraception, the follicular phase of the cycle may be associated with a higher frequency of HSV-2 shedding compared to the luteal phase. Lesion frequency is similar during the 2 menstrual phases. Hormonal contraception use was not observed to affect genital HSV-2 DNA detection or lesions.

The effect of hormonal contraception on genital herpes simplex virus-2 shedding and lesions

The effect of hormonal contraception on genital herpes simplex virus-2 shedding and lesions

LB1.5 Initial interactions of herpes simplex virus with human skin dendritic cells

Introduction The mechanism by which immunity to herpes simplex virus (HSV) is initiated is not completely defined. HSV initially infects the stratified squamous epithelium of the anogenital mucosa prior to entering nerve endings. We have recently reported that topical application of HSV-1 to human foreskin explants results in infection of epidermal Langerhans cells (LCs) which then emigrate into the dermis where they expressed the maturation marker CD80 and formed large cell clusters with BDCA3+ subsets of DC-SIGN+ and dermal dendritic cells (DCs) and. HSV-expressing LC fragments were observed inside the dermal DCs/macrophages. No other infected epidermal cells interacted with the dermal DCs (Kim et al. Plos Pathogens, 2015). Methods Therefore, we isolated LCs and dermal DCs from large abdominal skin specimens by collagenase digestion and flow sorting. LCs were pulsed with fluorescent tagged HSV and co-cultured with a subset of (BDCA3+) dermal DCs. Results All infected LCs showed markers of apoptosis at 18 hr p.i. Approximately 50% of BDCA3+ DCs co-localised with infected LCs and in some cases fragments of infected LCs were observed within the dermal DC cytoplasm. Such colocalizaton of HSV antigen bearing LCs and dermal DC subsets, was also detected within biopsies of initial genital herpes lesions. The mechanism of interaction of apoptotic LCs and dermal DCs, and uptake by phagocytosis are being determined. Conclusion Thus, a viral antigen relay takes place where HSV infected LCs slowly die by apoptosis during migration to the dermis and are taken up by dermal DCs by phagocytosis for subsequent antigen presentation. This provides a rationale for targeting these dermal DCs for mucosal or perhaps intradermal HSV immunisation. Disclosure of interest statement No pharmaceutical grants were received in the development of this study.

Herpes simplex virus type 2-infected dendritic cells produce TNF-α, which enhances CCR5 expression and stimulates HIV production from adjacent infected cells.

Prior HSV-2 infection enhances the acquisition of HIV-1 >3-fold. In genital herpes lesions, the superficial layers of stratified squamous epithelium are disrupted, allowing easier access of HIV-1 to Langerhans cells (LC) in the epidermis and perhaps even dendritic cells (DCs) in the outer dermis, as well as to lesion infiltrating activated T lymphocytes and macrophages. Therefore, we examined the effects of coinfection with HIV-1 and HSV-2 on monocyte-derived DCs (MDDC). With simultaneous coinfection, HSV-2 significantly stimulated HIV-1 DNA production 5-fold compared with HIV-1 infection alone. Because <1% of cells were dually infected, this was a field effect. Virus-stripped supernatants from HSV-2-infected MDDCs were shown to enhance HIV-1 infection, as measured by HIV-1-DNA and p24 Ag in MDDCs. Furthermore these supernatants markedly stimulated CCR5 expression on both MDDCs and LCs. TNF-α was by far the most prominent cytokine in the supernatant and also within HSV-2-infected MDDCs. HSV-2 infection of isolated immature epidermal LCs, but not keratinocytes, also produced TNF-α (and low levels of IFN-β). Neutralizing Ab to TNF-α and its receptor, TNF-R1, on MDDCs markedly inhibited the CCR5-stimulating effect of the supernatant. Therefore, these results suggest that HSV-2 infection of DCs in the skin during primary or recurrent genital herpes may enhance HIV-1 infection of adjacent DCs, thus contributing to acquisition of HIV-1 through herpetic lesions.

Relay of herpes simplex virus between Langerhans cells and dermal dendritic cells in human skin.

The mechanism by which immunity to Herpes Simplex Virus (HSV) is initiated is not completely defined. HSV initially infects mucosal epidermis prior to entering nerve endings. In mice, epidermal Langerhans cells (LCs) are the first dendritic cells (DCs) to encounter HSV, but it is CD103+ dermal DCs that carry viral antigen to lymph nodes for antigen presentation, suggesting DC cross-talk in skin. In this study, we compared topically HSV-1 infected human foreskin explants with biopsies of initial human genital herpes lesions to show LCs are initially infected then emigrate into the dermis. Here, LCs bearing markers of maturation and apoptosis formed large cell clusters with BDCA3+ dermal DCs (thought to be equivalent to murine CD103+ dermal DCs) and DC-SIGN+ DCs/macrophages. HSV-expressing LC fragments were observed inside the dermal DCs/macrophages and the BDCA3+ dermal DCs had up-regulated a damaged cell uptake receptor CLEC9A. No other infected epidermal cells interacted with dermal DCs. Correspondingly, LCs isolated from human skin and infected with HSV-1 in vitro also underwent apoptosis and were taken up by similarly isolated BDCA3+ dermal DCs and DC-SIGN+ cells. Thus, we conclude a viral antigen relay takes place where HSV infected LCs undergo apoptosis and are taken up by dermal DCs for subsequent antigen presentation. This provides a rationale for targeting these cells with mucosal or perhaps intradermal HSV immunization.

Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions

Herpes simplex virus (HSV) infection of the neonate is uncommon, but genital herpes infections in adults are very common. Thus, although treating an infant with neonatal herpes is a relatively rare occurrence, managing infants potentially exposed to HSV at the time of delivery occurs more frequently. The risk of transmitting HSV to an infant during delivery is determined in part by the mother's previous immunity to HSV. Women with primary genital HSV infections who are shedding HSV at delivery are 10 to 30 times more likely to transmit the virus to their newborn infants than are women with recurrent HSV infection who are shedding virus at delivery. With the availability of commercial serological tests that reliably can distinguish type-specific HSV antibodies, it is now possible to determine the type of maternal infection and, thus, further refine management of infants delivered to women who have active genital HSV lesions. The management algorithm presented herein uses both serological and virological studies to determine the risk of HSV transmission to the neonate who is delivered to a mother with active herpetic genital lesions and tailors management accordingly. The algorithm does not address the approach to asymptomatic neonates delivered to women with a history of genital herpes but no active lesions at delivery.

Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions

Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions

Population-Based Surveillance for Neonatal Herpes in New York City, April 2006–September 2010

Population-based data for neonatal herpes simplex virus (HSV) infection are needed to describe disease burden and to develop and evaluate prevention strategies. From April 2006 to September 2010, routine population-based surveillance was conducted using mandated provider and laboratory reports of neonatal HSV diagnoses and test results for New York City resident infants aged ≤60 days. Case investigations, including provider interviews and review of infant and maternal medical charts and vital records, were performed. Hospital discharge data were analyzed and compared with surveillance data findings. Between April 2006 and September 2010, New York City neonatal HSV surveillance detected 76 cases, for an average incidence of 13.3/100,000 (1/7519) live births. Median annual incidence of neonatal HSV estimated from administrative data for 1997 to 2008 was 11.8/100,000. Among surveillance cases, 90.8% (69/76) were laboratory confirmed. Among these, 40.6% (28/69) were HSV-1; 39.1% (27/69) were HSV-2; and 20.3% (14/69) were untyped. The overall case-fatality rate was 17.1% (13/76). Five cases were detected among infants aged >42 days. In all, 80% (20/25) of the case-infants delivered by cesarean section were known to have obstetric interventions that could have increased risk of neonatal HSV transmission to the infant before delivery. Over half (68%, or 52/76) of all cases lacked timely or ideal diagnostics or treatment. Administrative data may be an adequate and relatively inexpensive source for assessing neonatal HSV burden, although they lack the detail and timeliness of surveillance. Prevention strategies should address HSV-1. Incubation periods might be longer than expected for neonatal HSV. Cesarean delivery might not be protective if preceded by invasive procedures. Provider education is needed to raise awareness of neonatal HSV and to assure appropriate testing and treatment.

P3-S2.05 Invasive obstetric procedures and cesarean sections in women with known herpes simplex virus (HSV) status during pregnancy

BackgroundBreach of neonatal skin by obstetric procedures during delivery increases risk of neonatal herpes among infants of women with genital HSV infections. We hypothesised that knowledge of genital HSV infection...

Index of Suspicion in the Nursery

A 2.94-kg male infant is born at 39 weeks to a 19-year-old G1P0 woman. The pregnancy was complicated by gestational diabetes. The woman had no significant past medical history, including sexually transmitted diseases, and no significant family history. Prenatal screening for group B Streptococcus, Chlamydia, gonorrhea, syphilis, and human immunodeficiency virus were negative. Delivery is complicated by prolonged rupture of membranes for 18 hours, maternal fever (temperature of 38.9°C), and failure to progress. The baby is delivered in good condition by cesarean section. Apgar scores are 8 at 1 minute and 9 at 5 minutes. Vital signs are within normal limits, and physical examination at birth shows no abnormal findings of note. The infant is admitted to the newborn nursery for observation. Blood culture is drawn and empiric antibiotics are started. Hematologic parameters are within normal limits and C-reactive protein measures 0.5 mg/dL. Antibiotics are continued for suspected chorioamnionitis. He is otherwise feeding well, euthermic, and looking well, and his blood culture remains negative. On postnatal day 7, the nurse notices two vesicular skin lesions: one on the right side of the forehead (Fig. 1) and the other on the vertex of the scalp (Fig. 2). Both comprise groups of clustered tiny vesicles that have minimal erythema at their bases. Vital signs and physical examination findings are within normal limits. The result of a simple test supports the diagnosis, and further laboratory investigations confirm the cause. Figure 1. Vesicular lesions on the right side of the forehead. Figure 2. Vesicular lesions on the vertex of the scalp. # Case: Blister in a Baby: Benign or Bothersome? {#article-title-2} ### Differential Diagnosis Vesiculobullous lesions in neonates should never be ignored because the cause could range from benign, self-limited conditions to serious fatal diseases. Early diagnosis and management are crucial …

One-day famciclovir vs. placebo in patient-initiated episodic treatment of recurrent genital herpes in immunocompetent Black patients

Background:There are no known racial differences in genital herpes disease pathogenesis or response to therapy. Despite high herpes simplex virus (HSV) seroprevalence in Black persons, clinical trials investigating the treatment of recurrent genital herpes (RGH) have typically enrolled a small proportion of Black patients.Methods:This multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of patient-initiated, 1-day famciclovir 1000 mg twice-daily in immunocompetent Black adults (USA and South Africa) with RGH. Eligible patients were randomized (2:1) to famciclovir or placebo. The primary endpoint was time to healing of non-aborted genital herpes lesions (i.e., lesions that progressed beyond papule stage). Secondary endpoints included proportion of patients with aborted genital herpes lesions, time to resolution of associated symptoms, and safety.Clinical trial registration:Trial registration: ClinicalTrials.gov identifier: NCT00477334.Results:A total of 299 patients with RGH (66% female, median age = 37 years) received either 1-day famciclovir 1000 mg twice-daily (n = 201) or placebo (n = 98). In the modified intent-to-treat population, the estimated median time to healing of non-aborted genital herpes lesions was 5.38 days for famciclovir and 4.79 days for placebo (median of treatment differences = 0.26 days; 95% CI [−0.40, 0.98]; p = 0.416). Consistent findings were reported in the completer and per-protocol populations. No significant differences were reported for all secondary analyses. Adverse events (AEs) were consistent with the established safety profile of famciclovir: 18 (6%) patients had drug-related AEs (16 [8%] famciclovir; 2 [2%] placebo), none of which were serious or led to discontinuation or dose adjustment/interruption. There are some limitations of this research: many study sites either lacked prior experience in conducting clinical studies in patients with HSV infection or enrolled small numbers of patients, which may have compromised efficacy outcomes. Also, HIV antibody testing was not mandated at enrollment.Conclusion:This study showed similar efficacy and tolerability of 1-day treatment with famciclovir 1000 mg twice-daily compared to placebo in immunocompetent Black adults with RGH. Famciclovir has proven efficacy and safety in the overall RGH population. Further understanding of the efficacy of antiherpes therapy in Black patients with recurrent genital herpes may be warranted.

Single‐Day, Patient‐Initiated Famciclovir Therapy versus 3‐Day Valacyclovir Regimen for Recurrent Genital Herpes: A Randomized, Double‐Blind, Comparative Trial

Recurrent genital herpes is a major problem for patients worldwide. Early episodic treatment with short-course therapy is effective, often stopping progression of outbreaks. This study is the first head-to-head comparison of single-day famciclovir (1000 mg administered twice daily) versus 3-day valacyclovir (500 mg administered twice daily) for episodic therapy in immunocompetent patients. In this multicenter, multinational, double-blind, parallel-group study, 1179 adults with a history of recurrent genital herpes were randomized 1:1 to receive either famciclovir or valacyclovir. Patients initiated treatment within 6 h after a recurrence. The primary objective was to establish noninferiority of single-day famciclovir, compared with a 3-day course of valacyclovir, in time to healing of all nonaborted lesions in a modified intent-to-treat population. This study established that single-day famciclovir therapy was noninferior to 3-day valacyclovir therapy in reducing time to healing of all nonaborted genital herpes lesions (median time to healing, 4.25 days vs. 4.08 days). Approximately one-third of patients in each treatment group had aborted genital herpes episodes, suggesting that both treatments have similar efficacy in preventing outbreaks or progression of lesions beyond the papule stage. There was no significant difference in time to resolution of symptoms associated with recurrence. The overall incidence of adverse events was similar (23.2% for the famciclovir group vs. 22.3% for the valacyclovir group), with headache, nausea, diarrhea, vomiting, and abdominal pain reported most often. Single-day famciclovir (1000 mg administered twice daily) was similar to 3-day valacyclovir (500 mg administered twice daily) in both efficacy and safety, representing a more convenient treatment for immunocompetent adults with recurrent genital herpes.