Topical Acyclovir Research Articles

Acyclovir and post-herpetic neuralgia and ocular involvement.

Herpes zoster infection is a common clinical problem in elderly people. Three of the consequences of such infection are acute rash, post-herpetic neuralgia, and, for those with trigeminal infection, ocular complications. Post-herpetic neuralgia is a severe, prolonged, debilitating complication with no known effective treatment. Acyclovir treats acute rash,*RF 1-4* but its role in preventing post-herpetic neuralgia and ocular complications remains controversial. These complications can be severe and sight threatening and can require prolonged treatment. Topical acyclovir has been shown to be beneficial when given prophylactically and in established cases.5 We examined whether high oral doses of acyclovir (800 mg five times a day for seven days) have a beneficial effect on post-herpetic neuralgia and reduce ocular involvement in the long term. Of the …

(Mis)Treatment of Acute Herpes Zoster

Recent attention has been focused on new antiviral agents for the treatment of herpes zoster both in the medical literature 1 and in the lay press ( Wall Street Journal . July 12, 1933;B1, 5). Since acyclovir was approved for treatment of herpes zoster in April 1990, we have kept a log at the University of Texas Medical Branch, Galveston, of patients presenting at our clinics who inform us that they were previously treated for shingles by their local physician. Interestingly, only 33 (17%) of 197 of these patients had received acyclovir at the recommended dosage of 800 mg orally five times per day for 7 to 10 days. Another 56% of the patients reported being treated with acyclovir at lower oral dosages and/or with topical acyclovir. The remaining 27% of patients were treated with oral antibacterial agents and/or a variety of other non-antiviral drugs. As we actively enroll patients in clinical

Acanthamoeba Keratitis

Two patients presented with dendritiform epithelial irregularities of the cornea that were unresponsive to topical acyclovir. Both were soft contact lens wearers who had practiced inadequate lens hygiene. Acanthamoeba was cultured from a shallow corneal biopsy of one patient and from the contact lens of the other. Epithelial debridement resolved the condition in both patients without concomitant treatment with antiamoebic agents.

Epidermal Growth Factor in the Topical Treatment of Herpetic Corneal Ulcers

The tolerability and efficacy of epidermal growth factor (EGF) in the topical treatment of herpetic corneal ulcers in addition to topical acyclovir have been evaluated in a double-blind, placebo-controlled, randomized study in two groups of patients. The time required for complete reepithelialization of the cornea was recorded, and the data obtained were analyzed statistically. In the EGF group, the reepithelialization was significantly faster than in the control group. Tolerability of EGF was always excellent. These results indicate that EGF is safe and effective in reducing the healing time of herpetic corneal ulcers.

Acyclovir: is it an effective virostatic agent for orofacial infections?

Oral and intravenous acyclovir formulations provide effective virostasis against many herpes viruses infections, especially severe herpes simplex or varicella-zoster infections in ambulatory and immunocompromised patients. The therapeutic virostatic efficacy of topical acyclovir formulations requires further development, however, especially for orolabial herpetic infections.

An application of the [formula omitted] concept in predicting the topical efficacy of finite dose acyclovir in the treatment of cutaneous HSV-1 infections in hairless mice

This study has examined C ∗ (and its temporal pattern) as a parameter for predicting topical antiviral efficacy of acyclovir (ACV) formulations in a recently developed hairless mouse model for the treatment of HSV-1 cutaneous infections. C ∗ referred to here is the free drug concentration at the target site, which is believed to be the basal cell layer of the epidermis. Two different topical ACV formulations, one available commercially (Zovirax 5% ointment) and the other prepared in our laboratories (3% ACV suspension) were investigated in a finite dose multiple dosing regimen (twice a day application) to simulate the clinical situation. C ∗ was calculated from in vitro flux data and information obtained from previous baseline studies. In vitro ACV flux determinations involved an in vivo-in vitro experimental design that was believed to approximate closely the actual in vivo antiviral treatment protocol. For the in vivo antiviral efficacy studies, a 1-day delayed (after virus inoculation) 4-day treatment protocol was implemented and the animals wore a Velcro jacket to protect the formulations from being removed during the drug application period. With Zovirax 5% ointment given 3 mg every 12 h, our results showed a 0% topical efficacy which was consistent with the C ∗ predictions. In the case of the laboratory prepared 3% ACV suspension, a dose of 2 μl was given every 12 h and our results showed a modest level (33–44%) of topical effectiveness, which was somewhat higher than predicted (0–25%) from C ∗ considerations. Also, in the efficacy studies (but not in the in vitro flux studies) with the laboratory prepared formulation, there were instances (20–33%) of severe skin irritation/damage noted at the end (day 5) of the experiments. Taking this into consideration, it is suggested that these studies represent a good correlation between predictions (C ∗) based on the in vitro data and the in vivo antiviral efficacy and validate the predictive value of this approach.

Pharyngitis associated with herpes simplex virus in college students

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.

Management of genital herpes by genitourinary physicians: does experience or doctor's gender influence clinical management?

To determine the variation in management of genital herpes by genitourinary physicians, and whether their duration of experience or gender influence their clinical management. A postal questionnaire was sent to UK consultant genitourinary physicians with detailed questions about management of primary and recurrent herpes. The gender and duration of genitourinary medicine experience of the physicians were also recorded. One hundred and eighty two questionnaires were sent, 112 (62%) returned. Eighty-one (72%) physicians treat all patients with primary genital herpes, but physicians with more than 20 years experience were significantly (p < 0.05) more likely to treat only "severe" primary attacks. Most experienced physicians were also most likely (p < 0.05) to prescribe topical acyclovir. Prescription of suppressive acyclovir was also influenced by the experience of the physician, the least experienced physicians being more likely to prescribe to patients who were HIV antibody positive or to those entering new relationships, whereas the more experienced prescribed to those patients who were particularly anxious (p < 0.05 for each of these). Male physicians were significantly more likely to agree with the proposition that men cope better with genital herpes (54%) than female physicians (24%, p < 0.01). The response to the questionnaire illustrates that management of genital herpes is influenced by the duration of the physicians clinical experience. Gender of the physician may have an indirect role to play as we have shown that physicians differ in their perception of how the sexes cope with genital herpes.

Genital herpes: natural history and treatment of acute episodes.

Genital herpes is a common, distressing infection whose incidence has been underestimated. Recent serological surveys, employing type-specific antibody assays, show a rising prevalence of previous herpes simplex virus (HSV) type 2 infections in post-adolescent populations in developed countries; many of these infections have been asymptomatic. In some geographical locations, HSV-1 infections are a common cause of first episodes. They may occur in stable, monogamous relationships and are less likely to recur than genital infections caused by HSV-2. The clinical features of first episode genital herpes show marked individual variation in severity; they tend to be more severe in women than in men. Local and distant complications are common in immunocompetent individuals and may be life-threatening in those who are immunocompromised. The psychological and social consequences which result from the life-long infection and its risks of transmission to new sexual partners often prove more disabling to affected individuals than do the milder physical symptoms associated with recurrent episodes. Counselling, support, and patient education are essential components of management. Acyclovir is clearly established as the first choice therapy in both first and recurrent episodes of genital herpes. This drug has potent antiviral effect and provides significant clinical benefit in first episodes. Systemic therapy for initial episodes does not prevent either the establishment of latency or the development of future recurrences even when used in high or prolonged dosage. Episodic treatment of recurrences, with either oral or topical acyclovir, requires early patient initiation of therapy to provide significant clinical benefit.

Prophylactic chemotherapy with acyclovir for recurrent herpes simplex labialis.

The medical literature was reviewed and 11 clinical trials of prophylactic topical or peroral acyclovir for the suppression of recurrent herpes simplex labialis were identified. The results of these trials showed that prophylactic topical acyclovir was mostly ineffective, but that prophylactic peroral acyclovir, in doses ranging from 400 to 1,000 mg/day, reduced the frequency of herpes labialis during treatment by 50-78%. The reduction in the frequency of episodes of herpes labialis with acyclovir prophylaxis is less than the suppressive effect that has been reported for herpes genitalis (50-78% vs. 80-90%). In trials of prophylactic acyclovir for herpes labialis induced by experimental ultraviolet radiation, 26% of induced lesions developed within 48 hours of radiation exposure ("immediate" lesions) and, in contrast to "delayed" lesions that developed 2-7 days post-irradiation, were not suppressed by the antiviral compound. It is proposed that these treatment-unresponsive immediate lesions have an atypical pathogenesis, possibly involving latency of herpes simplex virus in the labial epithelium, and that these may be responsible for the apparent difference between herpes labialis and genitalis in the degree of benefit from prophylactic acyclovir therapy.

Management of ophthalmic zoster

The natural history of herpes zoster ophthalmicus and aspects of its treatment and prevention are presented. Intraocular complications occur in 50 percent of cases. Anterior uveitis and the various varieties of keratitis are commonest, affecting 92% and 52% of patients with ocular involvement, respectively. Sight-threatening complications include neuropathic keratitis, perforation, secondary glaucoma, posterior scleritis/orbital apex syndrome, optic neuritis, and acute retinal necrosis. Twenty-eight percent of initially involved eyes develop long-term ocular disease (6 months), with chronic uveitis, keratitis, and neuropathic ulceration being the commonest. Acute pain occurs in 93% of patients and is still present in 31% at 6 months. Of patients aged 60 and over pain persists in 30% for 6 months or longer, and this rises to 71% in those aged 80 and over. Current evidence favours the use of topical acyclovir alone for treatment of established ocular complications, with topical steroids being withheld in all but the most severe cases. Stellate ganglion block has proved useful in the treatment of established acute pain. Amitryptiline, and to a lesser extent sodium valproate, are useful in established chronic pain. Evidence of the efficacy of early oral acyclovir on ocular complications is conflicting, with two studies reporting significant improvement in differing disease parameters. A similar situation exists for pain, with published studies showing differing effects on pain at varying times after the onset of disease. The use of systemic steroids to prevent pain is not supported by currently available evidence, but its therapeutic relationship with acyclovir requires further evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term clinical and psychological management of genital herpes.

Many patients with genital herpes will have recurrences, and for some the recurrences may be frequent and severe and accompanied by profound psychosexual morbidity. Some patients can successfully be managed with intermittent courses of oral or topical acyclovir to be used with each recurrence. However this treatment is of limited efficacy, and longterm acyclovir suppression may be useful. This form of treatment is highly successful for patients with frequent recurrences most of whom will have no episodes during treatment. The optimum dosage for commencing acyclovir suppression is 200 mg four times daily, and the dose may subsequently be reduced. Some patients can successfully be managed on 400 mg twice daily. Treatment should be stopped after 1-2 years as there is some evidence of a decrease in the frequency of recurrences. Selecting patients for suppression should be based on the frequency, severity, and duration of recurrences as well as any associated emotional problems. Some patients may recur on suppression, usually due to inadequate dosage. Many patients with first episode genital herpes experience emotional and psychological problems. However these problems only continue if patients have recurrences and continued psychological support is essential. Long-term acyclovir suppression improves psychological well-being but is not a substitute for information, counselling, and expert psychosexual support.

Acyclovir Bioavailability in Human Skin

Clinical experience demonstrates that oral acyclovir (ACV) is superior to topical ACV in treating recurrent cutaneous herpes simplex virus type 1 (HSV-1) infections. Cutaneous HSV-1 infections are complex in their pathology, affecting the basal epidermis in skin as well as establishing a latency phase in sensory ganglia. In vitro and in vivo human skin model systems were used in the present study to quantitate ACV disposition and absorption in skin and blood following two routes of administration and to investigate whether bioavailability differences were the result of insufficient drug delivery. Physiochemical and physiologic parameters determined from these experiments were used to develop a mathematical model to predict ACV disposition and absorption in human subjects. Model predictions and in vivo data agree; topical administration of commercial 5% ACV ointment and cream result in a 48 times greater total epidermal ACV concentration than after oral administration. Mathematical modeling of the ACV concentration gradient through the epidermis revealed, however, that the drug concentration in the target site of HSV-1 infections, the basal epidermis, is 2-3 times less after topical administration than after oral administration. Thus, the observed lack of clinical efficacy with topical ACV therapy in the recurring HSV-1 infection likely reflects the insufficient delivery of the drug to the target site of the HSV-1 infection, the basal epidermis.

Double-masked trial of topical acyclovir and steroids in the treatment of herpes zoster ocular inflammation.

Ninety seven new patients with ophthalmic zoster were randomly allocated to three topical treatment groups: acyclovir (ACV) ointment and placebo drops (AP), placebo ointment with steroid drops (PS), and acyclovir ointment with steroid drops (AS). The dosage administered was determined by the score of the ocular inflammation. Follow-up was for at least one year. The results showed that topical ACV alone is insufficient for severe ocular inflammation but is not inclined to lead to recurrences in milder cases. Topical steroid alone is effective but tends to necessitate prolonged treatment. Combined steroid and ACV is questionably better than steroid alone and causes marginally fewer rebound inflammations.

The Natural History of Ultraviolet Radiation-Induced Herpes Simplex Labialis and Response to Therapy with Peroral and Topical Formulations of Acyclovir

The lips of 196 patients with a history of sun-induced herpes labialis were exposed to experimental ultraviolet radiation (UVR) and treated with acyclovir (ACV) or placebo at different times and by different routes. Of 98 placebo recipients, 39 (40%) developed 43 lesions inside or within 10 mm of the irradiated zone. The temporal distribution of lesions was bimodal. 11 (26%) occurring within 48 h (immediate) and 32 (72%) 2-7 days after UVR exposure (delayed). Prophylactic peroral ACV begun 7 days before or 5 min after UVR prevented the development of the delayed but not the immediate lesions (P less than .001). When peroral ACV was started 48 h after UVR, delayed lesions developed but were less severe (P = .01-.05). Prophylactic topical ACV begun 5 min after UVR did not reduce lesion frequency or severity. ACV therapy can be efficacious, but some rapidly developing lesions are unresponsive to treatment. This suggests that more than one process may contribute to the pathogenesis of herpes labialis.

Chronic ocular zoster

In a prospective open trial 40 patients suffering from acute herpes zoster ophthalmicus were treated with systemic acyclovir. An additional 10 patients were treated by topical acyclovir alone and dexamethasone eye-drops were administered to 5 of them to suppress ocular inflammation. In the topical treatment group the period of new skin lesion formation and progression of ocular inflammatory signs were significantly prolonged. Therapy with systemic acyclovir however resulted in a quick and complete resolution of ocular inflammation in all patients. Chronic ocular inflammation developed in 4 out of 10 patients treated with topical acyclovir. We consider chronic ocular zoster as a distinct clinical entity, possibly expressing a failing local immune response against VZV.

High-dose oral acyclovir in acute herpes zoster ophthalmicus: The end of the corticosteriod era

Systemic acyclovir (ACV), a new potent anti-herpes drug, was shown to reduce effectively the morbidity in the acute phase of herpes zoster ophthalmicus (AHZO). Using high dose oral ACV (5 X 800 mg/day) our aim in this study was: (1) to compare disease profiles in the ACV-treated group and in a group of zoster patients having had no ACV, analysed retrospectively; (2) to establish if high-dose ACV was able to prevent severe long term complications of AHZO; and (3) to determine the present role of corticosteroids in AHZO. From 1984 to 1988, 48 patients with AHZO of less than 3 days' duration were included. All patients received at least 7 days of oral ACV (5 X 800 mg/d) associated with topical ACV. Steroids were not given unless severe uveitis occurred. Follow-up was 2 years in 43 patients and 1 year in all 48 patients. Main conclusions from our study are: 1. Ocular involvement occurred in 67% of ACV-treated cases, a rate comparable to our retrospective group (59%) and to the literature (71%). However the rate of severe long term complications was minimal (4%) when compared to our non-treated retrospective group (21%). 2. Steroid treatment was not necessary in any of the ACV-treated patients. 3. ACV was well tolerated and did not have to be discontinued in any of the patients. High dose ACV and avoidance of steroids seems to eliminate the severe complications of AHZO.

Recurrent genital herpes in the guinea pig augmented by ultraviolet irradiation: Effects of treatment with acyclovir

The guinea pig model of genital herpes simplex virus infection has proven useful in the evaluation of antiviral drugs. We have recently demonstrated that recurrent herpetic infections can be induced in latently infected guinea pigs by ultraviolet irradiation. In this report we have examined the effect of acyclovir on ultraviolet radiation-induced recurrent genital herpes. Prophylactic topical acyclovir decreased the severity but not the incidence of ultraviolet radiation-induced recurrences while intraperitoneal acyclovir initiated before ultraviolet irradiation reduced both the incidence and severity of induced recurrences. When treatment was begun after ultraviolet exposure, neither topical nor intraperitoneal acyclovir were effective in reducing the incidence or severity of induced recurrent disease. The effectiveness of acyclovir in the control of induced recurrent genital infections in the guinea pig is similar to what has been observed in human trials. This model of ultraviolet radiation-induced recurrent herpes simplex virus infection should prove useful in the evaluation on new putative antiviral drugs.

Treatment of experimental ultraviolet radiation(UVR)-induced herpes labialis with peroral and topical acyclovir(ACV) : SL Spruance, DJ Freemanm, JCB Stewart, MB McKenough, G Wenerstrom, GG Krueger, and NH Rowe. U of Utahm Salt Lake Citym UT; U of Pittsburgh, Pittsburgh, PA; and U of Mich, Ann Arbor, MI, USA

Treatment of experimental ultraviolet radiation(UVR)-induced herpes labialis with peroral and topical acyclovir(ACV) : SL Spruance, DJ Freemanm, JCB Stewart, MB McKenough, G Wenerstrom, GG Krueger, and NH Rowe. U of Utahm Salt Lake Citym UT; U of Pittsburgh, Pittsburgh, PA; and U of Mich, Ann Arbor, MI, USA

Topical acyclovir cream in the treatmentof genital herpes

Topical acyclovir cream in the treatmentof genital herpes