Topical Acyclovir Therapy Research Articles

Effectiveness of photodynamic therapy as an adjunct to topical antiviral therapy in the treatment of herpes labialis: A randomized controlled clinical trial

BackgroundThe present clinical trial assessed the effectiveness of photodynamic therapy in association with topical acyclovir in the treatment of herpes labialis in adolescent patients. Materials and methods45 individuals with herpes labialis were divided into three groups on the basis of provision of treatment. (a) Group I: Topical acyclovir therapy (AVT) (n = 15, mean age: 17.5 years) (b) Group 2: photodynamic therapy (PDT) (n = 15, mean age:16.8 years) and (c) Group III: AVT + adjunctive PDT (n = 15, mean age: 17.0 years) respectively. HSV-1 quantification and pain scales [visual analogue scale (VAS) and McGill Pain Questionnaire (MPQ)] were calculated. Pro-inflammatory biomarkers including interleukin (IL-6) and tumor necrosis factor-alpha (TNF-α) were quantified using enzyme linked immunosorbent assay (ELISA). Shapiro-Wilk test was used to assess the normality. The Friedman test was employed to compute the comparison for changes recorded in pain scores, proinflammatory cytokines and HSV-1 quantification, whereas Mann-Whitney test was used to analyze the mean values and establish inter-group comparisons. All assessments were performed at baseline, immediate post op, 2-weeks, 4-weeks, 3-months, and 6-months. ResultsA total of 44 individuals completed the clinical trial. According to the data obtained from the clinical assessment, all the study groups reported a decrease in the parameters being observed. However, Group III (anti-viral (acyclovir) therapy + adjunctive PDT) showed a statistically significant decrease, in comparison to Group II (PDT) and Group I [AVT] respectively. The quantified HSV-1 among all groups showed significant reduction among all groups at each successive follow-up. However, Group-III (AVT + PDT) showed statistically significant reduction as compared to Groups I and II, respectively (p < 0.05). ConclusionTopical anti-viral therapy with adjunctive PDT significantly helped in reducing the pain and pro-inflammatory biomarkers in adolescent herpes labialis patients.

Herpetic ulcer of the eyelids in an immunocompromised patient

A 24-year-old black female (HIV-positive) was referred to our clinic with a 4-week history of an ulcerative lesion of the right upper and lower eyelids. She was on treatment for pulmonary tuberculosis and had been admitted to a secondary level hospital. She had no other ocular symptoms or signs. A tissue biopsy of the lesion revealed multinucleate squamous cells with ground glass viral nuclear inclusion bodies, indicative of herpes simplex virus (HSV) infection. The ulcer healed with oral and topical acyclovir therapy, confirming a herpetic origin. There is only one other reported case of this type of ulcerative eyelid lesion caused by HSV; the patient in this case was also immunocompromised.

Acyclovir Therapy in Prevention of Recurrent Herpetic Keratitis Following Penetrating Keratoplasty

To compare systemic vs topical acyclovir therapy for the prevention of recurrence of herpetic keratitis following penetrating keratoplasty (PK). A retrospective observational study. Patients who underwent PK for herpetic eye disease (HED) and prophylactically received acyclovir therapy postoperatively, either systemically (26 eyes) or topically (29 eyes), were analyzed. The main parameters evaluated were recurrence of herpetic keratitis, graft rejection, visual acuity, and graft survival rate. Mean average follow-up period was 24.7 +/- 3.6 months and 23.5 +/- 2.3 months in the systemic and topical group, respectively (P = 0.73). The average duration of prophylactic antiviral therapy in systemic group was 16.1 +/- 4.8 months and in topical group was 15.1 +/- 3.5 months (P = .59). Recurrence of herpetic keratitis was seen in 12% in the systemic group compared to 55% in the topical group (P < .001). More eyes in topical group 15 (52%) had rejection episodes than in the systemic group 5 (19%) (P < .001). A best-corrected visual acuity of > or = 20/40 was achieved in 31% and 7% eyes in the systemic and topical group, respectively, at the end of two years (P = .002). The clear graft survival rate in the systemic and topical acyclovir receiving group was 96.2% vs 86.2% at 12 months, and 88.5% vs 65.5% at 24 months, respectively. Systemic acyclovir is more effective than topical acyclovir in achieving better graft outcomes after PK for HED.

Pathogenicity and response to topical antiviral therapy in a murine model of acyclovir-sensitive and acyclovir-resistant herpes simplex viruses isolated from the same patient

Background Acyclovir-resistant herpes simplex viruses (HSV) are commonly recovered from immunocompromised individuals who exhibit chronic and/or disseminated herpetic lesions. Objectives and study design The virulence and response to topical acyclovir therapy were evaluated in a mouse model of zosteriform cutaneous HSV infection using two HSV-1 isolates from the same immunocompromised patient (one susceptible and one resistant to acyclovir). Results The acyclovir-resistant virus, with a Thr63Ile change in the ATP-binding site of the thymidine kinase gene, produced almost as many skin lesions as the wild-type susceptible virus. As expected from in vitro susceptibility data, the herpetic lesions of the mice infected with the drug-resistant virus did not respond to topical acyclovir therapy. Conclusions Some thymidine kinase HSV mutants associated with drug resistance may retain their pathogenicity at least in the mouse model described in this study.

Management of genital herpes.

Oral acyclovir is the therapy of choice for treatment of first-episode genital herpes, for suppression of frequently recurrent genital herpes, and, in selected patients, for episodic treatment of recurrent genital herpes. Topical acyclovir therapy is relatively or totally ineffective and is therefore discouraged. Indications for intravenous acyclovir therapy of mucocutaneous HSV infections include patients hospitalized with severe first-episode genital herpes and immunocompromised patients who have severe infections or who cannot swallow the oral preparation. The most promising investigational drugs are the oral prodrugs valaciclovir and famciclovir. Famciclovir is licensed in the U.S. for treatment of zoster but not for treatment of mucocutaneous genital herpes. When used for episodic therapy of recurrent genital herpes, both famciclovir and valaciclovir effectively reduce the duration of viral shedding, lesion healing times, and the duration of symptoms. Suppressive therapy with famciclovir has also been shown to be effective in reducing the frequency of episodes in women with frequently recurring genital herpes. Although these drugs can be given less frequently than oral acyclovir, there is yet no clear indication that they are more effective or better tolerated than oral acyclovir.

Topical Interferon Alpha-2A Treatment of Herpes Simplex Keratitis Resistant to Multiple Antiviral Medications in an Immunosuppressed Patient

The treatment of herpes simplex keratitis has ranged from simple debridement to the use of prototypic antiviral agents specific to the herpes family, such as acyclovir. The various treatment modalities for dendritic keratitis, for the most part, have been effective. However, in recent years numerous reports of antiviral-resistant strains of herpes simplex have appeared, particularly in immunocompromised patients receiving chronic acyclovir. Interferon has been proposed as a possible treatment adjunct in these cases. We report the case of a 46-year-old man on chronic immunosuppressive and acyclovir therapy after a renal transplant who developed ulcerative keratitis due to a strain of herpes simplex virus that was resistant to multiple antiviral agents both in vivo and in vitro. After 7 weeks without improvement on multiple treatment regimens, including trifluridine, vidarabine, debridement, and topical and systemic acyclovir, interferon alpha-2a was added to topical acyclovir therapy, and the keratitis quickly resolved. Topical interferon alpha-2a appears to be an effective treatment adjunct for refractory herpes simplex keratitis in patients with cell-mediated immune dysfunction and subsequent lack of endogenous interferon. Its value in nonimmunocompromised patients remains to be determined.

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.

Characterization of acyclovir-resistant and -sensitive herpes simplex viruses isolated from a patient with an acquired immune deficiency.

Several different genital and non-genital HSV isolates were obtained from a patient with an acquired immune deficiency of unknown aetiology. The patient was initially treated with topical acyclovir (ACV) and later with topical and intravenous ACV. In spite of treatment with antiviral drugs the patient continued to shed virus and to have extensive genital ulcerations. Restriction endonuclease (RE) analyses of the viral DNA revealed that all the isolates had characteristic HSV-2 patterns and that there were three genetically distinct virus groups among the ten isolates tested. Three post-therapy isolates, with the same RE pattern, were found to be devoid of thymidine kinase activity (TKD), highly resistant to ACV in cell culture, but sensitive to vidarabine (ara-A), phosphonoacetate and phosphonoformate. Two of these TKD isolates were obtained during and after topical ACV therapy and before intravenous treatment. Mice inoculated intracerebrally with a lethal dose of each of the three TKD viruses were refractory to ACV, but responded to vidarabine or a combination of ACV and ara-A. Mice inoculated with the TK+ viruses (including the pre-therapy isolate) responded to ACV and/or ara-A treatment. The results indicate that: (i) TKD variants may be produced in humans after topical ACV therapy; (ii) different ACV-resistant or sensitive HSV-2 variants can establish latency at different body sites and reactivate; and (iii) when drug-resistant viruses are isolated from patients with multiple reactivations, the drug in question should not be discontinued, since the patients may also be shedding drug-sensitive virus at a different body site.

Evaluation of the antiherpetic activity of acyclovir in rabbits

Acyclovir (3 percent ointment) used topically one to five times a day on acute ocular herpes simplex virus (HSV) infection gave beneficial results as measured by a reduction in corneal involvement, conjunctivitis, iritis, and corneal clouding. Early intensive acyclovir topical treatment every two hours beginning 24 hours after inoculation prevented all but conjunctivitis. Topical treatments did not prevent the establishment of latent HSV infection. Effects of topical acyclovir treatment on rabbit eyes infected with parent McKrae, idoxuridine-resistant, and vidarabine-resistant strains of HSV-1 were studied. Topical acyclovir therapy given four times a day was significantly more effective than idoxuridine and vidarabine in suppressing acute herpetic ocular disease induced by either sensitive or drug-resistant strains of HSV-1. Virus isolation from neural tissues indicated that none of the therapy prevented viral infection of the nervous system. Intravenous acyclovir used twice a day (50 mg/kg) on rabbits with latent HSV infection appeared to suppress HSV in the nervous system but did not eradicate established latent HSV infection.