Abstract/Text
Sunlight exposure is reported by some patients to precede onset of recurrent herpes labialis. Ultraviolet (UV) B light is known to be a stimulus for the reactivation of herpes simplex virus (HSV) infections. We assessed the effect of a sunblocking agent on UV-light-induced reactivation of recurrent herpes labialis in a double-blind, placebo-controlled crossover trial. 38 patients were exposed on two separate occasions to four minimum erythema doses of UV light at an area of previous labial herpes recurrence. A solution containing sunscreen was applied to the lips before one exposure and a matched placebo before the other. After placebo and UV exposure, herpes labialis developed in 27 (71%) of the 38 patients, with a mean time to recurrence of 2.9 (SEM 0.2) days. In contrast, when sunscreen was applied before UV exposure, no lesions developed, but 1 of the 35 patients shed virus at the exposure site. We conclude that UV light is a potent stimulus for inducing reactivation of herpes labialis, and that application of sunscreen may be effective in the prevention of sunlight-induced recurrent infection.
Abstract/Text
Immunopathology is recognized as an important component of infectious disease manifestations, and corticosteroids have been used as an adjunct to antimicrobial therapy for a variety of conditions. Antiviral therapy of herpes labialis has been shown to result in only a small reduction in the time to healing and the duration of pain. To determine if topical application of a combination product containing 5% acyclovir and 1% hydrocortisone (ME-609) could provide benefit to herpes labialis patients, 380 immunocompetent adults with a history of herpes labialis were exposed to experimental UV radiation (UVR) to induce a recurrence. On day 2, just before the appearance of the majority of lesions ("delayed" lesions), subjects were randomized to receive active medication or vehicle control six times per day for 5 days. Overall, 120 of 380 patients developed delayed classical lesions, of whom 50 of 190 (26%) had been treated with ME-609 and 70 of 190 (37%) had received placebo (a reduction of 29% [P = 0.02]). Healing time, measured as the time to normal skin, was reduced by treatment with ME-609 (9.0 days for treated patients versus 10.1 days for the controls [P = 0.04]). There was a trend toward a reduction in the maximum lesion size in the ME-609 recipients compared to that in the controls (43 versus 60 mm(2), respectively [P = 0.07]). The treatment had no effect on lesion pain, but ME-609 treatment reduced the number of patients with moderate or severe tenderness. Compared to treatment with a placebo, treatment with the combination antiviral-immunomodulatory cream provided benefit to patients with experimental UVR-induced herpes labialis, reducing classical lesion incidence, healing time, lesion size, and lesion tenderness. ME-609 is a novel product that merits further evaluation as a treatment for cold sores.
Abstract/Text
OBJECTIVE: A three-center, randomized, double-blind, placebo-controlled acyclovir clinical trial was conducted among Canadian skiers over a 2-year period.
STUDY DESIGN: All patients enrolled in the study reported a history of recurrent herpes labialis with a greater-than-50% chance of a sun-induced trigger. There were 239 patients enrolled, and 237 of these were included in the analysis. For a minimum of 3 days and a maximum of 7 days, each patient received 800 mg of oral acyclovir twice daily (1600 mg/day) 12 to 24 hours before exposure to the sun. A minimum of 3 hours of outdoor activity was required each day.
RESULTS: No differences were detected in baseline and outcome measures among the centers, and results from all three centers were combined for further analysis. There was no difference in healing rate between the acyclovir and placebo groups for the first 4 days. Patients using acyclovir healed slightly faster on days 5 and 6, and nearly all patients in both the acyclovir and placebo groups were healed by day 7. Adverse events were evenly distributed; no withdrawals were required in either group.
CONCLUSION: 800-mg oral acyclovir taken twice a day was not significantly better than a placebo either in effectiveness and prevention of recurrent herpes labialis or in adverse effects.
Abstract/Text
To determine the effectiveness of an antiviral to prevent herpes labialis during a brief, high-risk circumstance, 147 persons with a history of sun-induced recurrences were treated prophylactically with oral acyclovir or matching placebo and were observed during their ski holidays. Five (7%) of 75 acyclovir-treated subjects developed lesions compared with 19 (26%) of 72 persons in the placebo group.
Abstract/Text
BACKGROUND: Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis.
OBJECTIVES: To compare the relative effectiveness of antiviral agents, interferon, and corneal débridement in the treatment of acute HSV epithelial keratitis.
SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library 2010, Issue 4), MEDLINE (January 1950 to October 2010), EMBASE (January 1980 to October 2010), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2010), Zetoc (British Library's Electronic Table of Contents), System for Information on Grey Literature in Europe (openSIGLE), Biosciences Information Service (BIOSIS), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), Japan Information Center of Science and Technology (JICST-EPlus), and China Academic Journals database (CAJ) via China National Knowledge Infrastructure (CNKI) with citations confirmed using China/Asia On Demand (COAD). There were no language or date restrictions in the search for trials. All databases except CNKI and COAD were last searched on 27 October 2010, CNKI and COAD were searched on 1 April 2010. We also searched literature digests, conference proceedings and reference lists.
SELECTION CRITERIA: Of 152 eligible studies,106 comparative treatment trials involving 5872 eyes with dendritic or geographic epithelial keratitis were analysed for corneal healing over two weeks.
DATA COLLECTION AND ANALYSIS: Interventions were compared at 14 days after trial enrolment by calculating a risk ratio (RR) that was adjusted with indirect RR, assessed by an inconsistency index (I(2) ) and supplemented by a seven-day RR and a hazard ratio (HR).
MAIN RESULTS: Idoxuridine, though uncertainly better in healing outcome than control because of few trials with 14-day follow up, allowed earlier corneal re-epithelialisation. Vidarabine resulted in a significantly better outcome than placebo in one trial (RR 1.96; 95% CI 1.10 to 3.49). Compared to idoxuridine, in combined direct and indirect analyses, vidarabine (RR 1.11; 95% CI 1.03 to 1.19), trifluridine (RR 1.31; 95% CI 1.20 to 1.42), acyclovir (RR 1.23; 95% CI 1.16 to 1.31), brivudine (RR 1.38; 95% CI 1.18 to 1.61), and ganciclovir (RR 1.40; 95% CI 1.25 to 1.57) were significantly more effective. Trifluridine (RR 1.12; 95% CI 1.04 to 1.21) and acyclovir (RR 1.11; 95% CI 1.05 to 1.19) appeared more effective than vidarabine. No significant differences were found in comparisons between acyclovir, trifluridine and brivudine. The comparison of ganciclovir to acyclovir was limited by heterogeneity and possible publication bias. The joint use of two topical antivirals (RR 1.00; 95% CI 0.89 to 1.12) and the use of oral acyclovir alone (RR 0.92; 95% CI 0.79 to 1.07) or combined with a topical antiviral (RR 1.08; 95% CI 0.99 to 1.17) appeared as effective as topical antiviral therapy. Compared to antiviral monotherapy, the combination of an antiviral with interferon (RR 1.03; 95% CI 0.99 to 1.07) or with débridement (RR 1.04; 95% CI 0.95 to 1.14) did not yield significantly better outcomes but may have accelerated healing. The corneal epithelial healing outcome was improved when antiviral therapy was added to débridement (RR 1.21; 95% CI 1.04 to 1.42).
AUTHORS' CONCLUSIONS: Trifluridine and acyclovir are more effective than idoxuridine or vidarabine, and similar in therapeutic effectiveness. Brivudine and ganciclovir are at least as effective as acyclovir. While not improving outcome, the combination of interferon and an antiviral agent may speed healing. The effectiveness of corneal epithelial débridement is improved by an antiviral agent.
Abstract/Text
During a 16-month period patients who presented to the Syracuse University Health Center with upper respiratory complaints had throat swabs obtained for viral, streptococcal and Mycoplasma pneumoniae cultures. Thirty-five of 613 patients (5.7%) had herpes simplex virus (HSV) isolated. All but 2 of the HSV isolates were found to be type 1 by immunofluorescent staining. Two HSV-positive patients also grew Group A Streptococcus, one grew M. pneumoniae and three had serum heterophile antibody tests that were positive. On physical examination 25 of the 35 HSV-positive patients had pharyngeal erythema and 14 had pharyngeal exudate. Twelve of these patients had vesicular lesions of the lips, throat or gums associated with their other symptoms. For 29 of the 35 HSV-positive students the primary diagnosis assigned was pharyngitis, for 2 the diagnosis was stomatitis and the remainder were assigned a primary diagnosis of upper respiratory infection, pneumonia, bronchitis or dental infection. Thirty-two of the 35 HSV-positive patients were treated with oral antibiotics and 7 were treated with oral or topical acyclovir. During the same 16-month period 89 (6.9%) of 1297 students presenting with sore throat were culture-positive for influenza A or B, 30 (2.3%) of 1283 were culture-positive for M. pneumoniae and 169 (2.8%) of the 6016 cultured for Group A Streptococcus were positive. Serum was tested for heterophile antibody in 2438 students, and 257 (10.5%) were positive. Herpes simplex virus is associated with pharyngeal symptoms in college students, and herpes simplex pharyngitis cannot easily be distinguished clinically from other causes of acute pharyngitis in this age group.
Abstract/Text
OBJECTIVES: To examine the efficacy of aciclovir suspension for treating herpetic gingivostomatitis in young children.
DESIGN: Randomised double blind placebo controlled study.
SETTING: Day care unit of a tertiary paediatric hospital.
SUBJECTS: 72 children aged 1-6 years with clinical manifestations of gingivostomatitis lasting less than 72 hours; 61 children with cultures positive for herpes simplex virus finished the study.
MAIN OUTCOME MEASURES: Duration of oral lesions, fever, eating and drinking difficulties, and viral shedding.
INTERVENTION: Aciclovir suspension 15 mg/kg five times a day for seven days, or placebo.
RESULTS: Children receiving aciclovir had oral lesions for a shorter period than children receiving placebo (median 4 v 10 days (difference 6 days, 95% confidence interval 4.0 to 8.0)) and earlier disappearance of the following signs and symptoms: fever (1 v 3 days (2 days, 0.8 to 3.2)); extraoral lesions (lesions around the mouth but outside the oral cavity) (0 v 5.5 days (5.5 days, 1.3 to 4.7)); eating difficulties (4 v 7 days (3 days, 1.31 to 4.69)); and drinking difficulties (3 v 6 days (3 days, 1.1 to 4.9)). Viral shedding was significantly shorter in the group treated with aciclovir (1 v 5 days (4 days, 2.9 to 5.1)).
CONCLUSIONS: Oral aciclovir treatment for herpetic gingivostomatitis, started within the first three days of onset, shortens the duration of all clinical manifestations and the infectivity of affected children. Further studies are needed to evaluate the ideal dose and length of treatment.
Abstract/Text
BACKGROUND: Reactivation of herpes simplex virus-1 (HSV-1) after facial resurfacing has led to severe outbreaks, delayed reepitheliazation, and scarring. Current recommendations regarding the dosing of antivirals used prophylactically are based mostly on anecdotal experience. No studies have addressed the question of when such antiviral prophylaxis should begin.
OBJECTIVE: The purpose of this study was to compare the efficacy of valacyclovir used as an antiviral prophylaxis when started the morning before versus the morning of facial resurfacing procedures.
METHODS: Eighty-four patients who presented for facial resurfacing were enrolled. Resurfacing was performed using laser (CO2, Er:YAG), chemical peeling, dermabrasion/dermasanding, or some combination of these techniques. Patients were randomly assigned to start valacyclovir 500 mg twice daily either the morning before or the morning of the procedure. Viral cultures were performed at baseline on all patients, at any sign of infection, and at the end of the 14-day treatment period. All patients were followed for 21 days postoperatively.
RESULTS: Valacyclovir was 100% effective in the prevention of HSV reactivation in both regimens with no adverse effects reported.
CONCLUSION: This study demonstrates the efficacy of valacyclovir as a preventive agent against HSV outbreaks following facial resurfacing whether started the day before or the day of surgery.
Abstract/Text
Acyclovir was shown to limit herpes simplex reactivation in a controlled trial to prevent herpes labialis after surgical intervention for trigeminal neuralgia. Of 14 patients receiving acyclovir, unambiguous herpes labialis developed in only one, compared with 12 of 16 in the placebo group.
Abstract/Text
BACKGROUND AND METHODS: Most strains of herpes simplex virus that are resistant to acyclovir are susceptible in vitro to both foscarnet and vidarabine. We conducted a randomized trial to compare foscarnet with vidarabine in 14 patients with the acquired immunodeficiency syndrome (AIDS) and mucocutaneous herpetic lesions that had been unresponsive to intravenous therapy with acyclovir for a minimum of 10 days. The patients were randomly assigned to receive either foscarnet (40 mg per kilogram of body weight intravenously every 8 hours) or vidarabine (15 mg per kilogram per day intravenously) for 10 to 42 days. In the isolates of herpes simplex virus we documented in vitro resistance to acyclovir and susceptibility to foscarnet and vidarabine.
RESULTS: The lesions in all eight patients assigned to foscarnet healed completely after 10 to 24 days of therapy. In contrast, vidarabine was discontinued because of failure in all six patients assigned to receive it. The time to complete healing (P = 0.01), time to 50 percent reductions in the size of the lesions (P = 0.01) and the pain score (P = 0.004), and time to the end of viral shedding (P = 0.006) were all significantly shorter in the patients assigned to foscarnet. Three patients had new neurologic abnormalities while receiving vidarabine. No patient discontinued foscarnet because of toxicity. Although initial recurrences of herpes simplex infection after the index lesion had healed tended to be susceptible to acyclovir, acyclovir-resistant infection eventually recurred in every healed patient, a median of 42.5 days (range, 14 to 191) after foscarnet was discontinued.
CONCLUSIONS: For the treatment of acyclovir-resistant herpes simplex infection in patients with AIDS, foscarnet has superior efficacy and less frequent serious toxicity than vidarabine. Once the treatment is stopped, however; there is a high frequency of relapse.
Abstract/Text
In a double-blind, randomized, patient-initiated clinical trial, 174 nonimmunocompromised patients with a history of virus-culture-confirmed herpes simplex labialis were treated with acyclovir capsules, 400 mg five times daily for 5 days, or placebo capsules. For 97% of the patients, treatment started within 1 h of the first sign or symptom of a recurrence. The frequency of positive lesion virus cultures was significantly lower among acyclovir-treated subjects (29/114, 25%) than among placebo-treated subjects (29/60, 48%; P = .004). Drug treatment did not affect the development of lesions, measured by the frequency of macular and papular (aborted) lesions and mean maximum lesion size. However, acyclovir hastened lesion resolution among the patients who could start treatment in the prodrome or erythema lesion stage. For this group, the mean duration of pain was reduced by 36% (P = .02) and the mean healing time to loss of crust by 27% (P = .03). Thus, oral acyclovir alleviated some of the clinical manifestations of herpes simplex labialis.
Abstract/Text
OBJECTIVE: To determine whether oral acyclovir reduces the incidence of recurrent herpes labialis in otherwise healthy patients with proven frequently recurrent disease.
DESIGN: Randomized, double-blind, placebo-controlled, crossover trial.
SETTING: Outpatient facility of the Clinical Center, National Institutes of Health, Bethesda, Maryland.
PATIENTS: Fifty-six otherwise healthy adults who reported frequently recurrent herpes labialis (> or = 6 episodes/y) were enrolled into the study. During a 4-month observation period, 22 patients had herpes labialis two or more times and were eligible for study treatment.
INTERVENTIONS: Twenty-two patients were randomized to receive either acyclovir, 400 mg twice daily, or matched placebo for 4 months. After the first treatment period, patients were given the alternate treatment for another 4 months and were then taken off study medication to observe the first post-treatment recurrence. Recurrent outbreaks were determined by examination and by viral culture.
RESULTS: Twenty patients completed blind treatment with both acyclovir and placebo. The median time to first clinically documented recurrence was 46 days for placebo courses and 118 days for acyclovir courses (P = 0.05). The mean number of recurrences per 4-month treatment period was 1.80 episodes per patient during placebo treatment and 0.85 episodes per patient during acyclovir treatment (P = 0.009). The mean number of virologically confirmed recurrences per patient was 1.40 with placebo therapy compared with 0.40 with acyclovir (P = 0.003).
CONCLUSIONS: Oral acyclovir, 400 mg twice daily, is effective in suppressing herpes labialis in immunocompetent adults confirmed to have frequently recurrent infection. Treatment with acyclovir in this study resulted in a 53% reduction in the number of clinical recurrences and a 71% reduction in virus culture-positive recurrences compared with placebo therapy.
Abstract/Text
The oral antiviral valacyclovir, which is 3 to 5 times more bioavailable than its parent compound acyclovir, is a good candidate for effective therapy to suppress recurrent herpes labialis lesions. The efficacy of oral valacyclovir in the suppression of herpes labialis has not previously been reported. Two identical, randomized, double-blind, parallel-group studies were conducted to evaluate the efficacy of oral valacyclovir 500 mg (n=49) versus placebo (n=49) once daily for 16 weeks in the suppression of herpes labialis among patients with a history of 4 or more recurrent lesions in the previous year. Data from the studies were pooled for analysis. Twenty-eight patients (60%) in the valacyclovir group compared with only 18 patients (38%) in the placebo group were recurrence-free throughout the 4-month treatment period (P=.041). The mean time to first recurrence was significantly longer with valacyclovir (13.1 weeks) compared with placebo (9.6 weeks) (P=.016). The total number of recurrences in patients using valacyclovir was 24 compared with 41 in patients using placebo. The incidence of adverse events during the 4-month treatment period was slightly lower in the valacyclovir group (22 events, 33% of patients) compared with the placebo group (29 events, 39% of patients). The results of these small double-blind, placebo-controlled studies suggest that oral valacyclovir 500 mg once daily for 4 months is effective and well tolerated for the prevention of recurrent herpes labialis. More research with larger patient numbers is warranted to corroborate and extend these findings.
Spotswood L Spruance, Terry M Jones, Mark M Blatter, Mauricio Vargas-Cortes, Judy Barber, Joanne Hill, Donna Goldstein, Margaret Schultz
High-dose, short-duration, early valacyclovir therapy for episodic treatment of cold sores: results of two randomized, placebo-controlled, multicenter studies.
Antimicrob Agents Chemother. 2003 Mar;47(3):1072-80.
Abstract/Text
Oral valacyclovir is better absorbed than oral acyclovir, increasing acyclovir bioavailability three- to fivefold. This provides the opportunity to explore whether high systemic acyclovir concentrations are effective in the treatment of cold sores (herpes labialis). Two randomized, double-blind, placebo-controlled studies were conducted. Subjects were provided with 2 g of valacyclovir twice daily for 1 day (1-day treatment), 2 g of valacyclovir twice daily for 1 day and then 1 g of valacyclovir twice daily for 1 day (2-day treatment), or a matching placebo and instructed to initiate treatment upon the first symptoms of a cold sore. In study 1, the median duration of the episode (primary endpoint) was reduced by 1.0 day (P = 0.001) with 1-day treatment and 0.5 days (P = 0.009) with 2-day treatment compared to placebo. Similarly, the mean duration of the episode was statistically significantly reduced by 1.1 days with 1-day treatment and 0.7 days with 2-day treatment compared to placebo. The proportion of subjects in whom cold sore lesion development was prevented and/or blocked was increased by 6.4% (P = 0.096) with 1-day treatment and 8.5% (P = 0.061) with 2-day treatment compared to placebo. The time to lesion healing and time to cessation of pain and/or discomfort were statistically significantly reduced with valacyclovir compared to placebo. In study 2, results similar to those in study 1 were obtained. AEs were similar across treatment groups. These studies provide evidence supporting a simple, 1-day valacyclovir treatment regimen for cold sores that is safe and effective. The 1-day valacyclovir regimen offers patients a unique and convenient dosing alternative compared to available topical therapies.
Abstract/Text
Acyclovir cream has been available for the treatment of herpes labialis in numerous countries outside the United States for over a decade. Evidence for its efficacy comes from a few small clinical trials conducted in the 1980s. To examine more comprehensively the efficacy and safety of this formulation, we conducted two independent, identical, parallel, randomized, double-blind, vehicle-controlled, large-scale multicenter clinical trials. Healthy adults with a history of frequent herpes labialis were recruited from the general population, screened for eligibility, randomized equally to 5% acyclovir cream or vehicle control, given study medication, and told to self-initiate treatment five times daily for 4 days beginning within 1 h of the onset of a recurrent episode. The number of patients who treated a lesion was 686 in study 1 and 699 in study 2. In study 1, the mean duration of episodes was 4.3 days for patients treated with acyclovir cream and 4.8 days for those treated with the vehicle control (hazards ratio [HR] = 1.23; 95% confidence interval [CI], 1.06 to 1.44; P = 0.007). In study 2, the mean duration of episodes was 4.6 days for patients treated with acyclovir cream and 5.2 days for those treated with the vehicle control (HR = 1.24; 95% CI, 1.06 to 1.44; P = 0.006). Efficacy was apparent whether therapy was initiated "early" (prodrome or erythema lesion stage) or "late" (papule or vesicle stage). There was a statistically significant reduction in the duration of lesion pain in both studies. Acyclovir cream did not prevent the development of classical lesions (progression to vesicles, ulcers, and/or crusts). Adverse events were mild and infrequent.
