Mark B. McKeough

Combination Treatment with Famciclovir and a Topical Corticosteroid Gel versus Famciclovir Alone for Experimental Ultraviolet Radiation-Induced Herpes Simplex Labialis: A Pilot Study

To investigate the efficacy of corticosteroids for the treatment of herpes labialis, we compared famciclovir (Famvir, 500 mg 3x/day po [per os] for 5 days) and topical fluocinonide (0.05% Lidex Gel 3x/day for 5 days) with famciclovir and topical vehicle control for experimental ultraviolet radiation-induced herpetic recurrences. We irradiated 49 volunteers, and 29 (60%) of 48 developed signs or symptoms of a recurrence. They self-initiated treatment, and we were able to evaluate them. There was a trend in the combination group toward more aborted lesions, compared with those who received antiviral therapy alone (7 [41%] of 17 vs. 1 [8%] of 12; P=.09). Combination therapy significantly reduced the median maximum lesion size (48 vs. 162 mm(2); P=.02) and the number of patients who experienced lesion pain (10 [59%] of 17 vs. 12 [100%] of 12; P=.02). Adverse events were minimal. Corticosteroids in combination with an antiviral agent may be safe and beneficial for episodic treatment of herpes labialis. Larger studies are needed to confirm these findings.

Th1Th2-like immunity and resistance to herpes simplex labialis

To investigate potential immunologic mechanisms of resistance to recurrent herpes simplex labialis, we assayed serum antibody titers and cultured peripheral blood mononuclear cell (PBMC) cytokine production among patients with a history of frequent episodes (H+S+), herpes simplex virus (HSV)-seropositive individuals without a history of herpes labialis (H-S+) and HSV-seronegative persons (H-S-). In addition, H+S+ patients were exposed to experimental ultraviolet radiation (UVR) on the lips and the immunologic assay results compared among those who developed experimental lesions and those who did not. H+S+ patients were found to have higher median serum titers of HSV antibody and trends to lower levels of HSV-specific PBMC IFN-gamma and IL-2 than H-S+ control patients (123 vs 66, P = 0.04; 424 vs 548 pg/ml, P = 0.08; 14 vs 26 pg/ml, P = 0.14, respectively). Correlation of the results with the occurrence of experimental lesions showed the inverse: the subgroup of H+S+ patients with UVR-induced lesions had lower titers of antibody and trends to higher levels of IFN-gamma and IL-2 than H+S+ patients who could not be induced (93 vs 149, P = 0.02; 501 vs 347 pg/ml, P = NS; 26 vs 11 pg/ml, P = NS, respectively). The size and duration of UVR-induced lesions showed positive correlations with IFN-gamma and IL-2 levels (r = 0.60-0.67, P = 0.02-0.04). Although the small number of patients limited the power of this study, the overall pattern of the findings suggests that a Th1-like cytokine response (IFN-gamma and IL-2 production) may be associated with resistance to naturally occurring episodes of herpes labialis. The development and severity of experimental UVR-induced herpes labialis appears to be regulated differently and may involve an immunopathologic mechanism.

Treatment of acyclovir-unresponsive cutaneous Herpes simplex virus infection with topically applied SP-303

The naturally occurring polyphenolic biopolymer SP-303 has in vitro activity against both HSV-1 and HSV-2, including strains that are resistant to acyclovir. Nine AIDS patients with acyclovir-unresponsive mucocutaneous herpes simplex virus infection were treated with thrice daily topical SP-303T ointment in an open-label pilot study. Although a transient decrease in lesion size was observed in 4 patients during study drug therapy, and 3 patients sustained a quantitative decrease in virus burden, neither complete healing nor cessation of virus shedding occurred in any patient. Seven patients complained of pain or burning upon application of the study ointment, causing 1 patient to terminate the study. In summary, application of SP-303T ointment effected no significant improvement in the clinical course of 9 AIDS patients with acyclovir-unresponsive HSV infection.

Valacyclovir and topical clobetasol gel for the episodic treatment of herpes labialis: a patient-initiated, double-blind, placebo-controlled pilot trial.

Background  Treatment of herpes simplex labialis (HSL) has been associated with modest benefits. This difficulty results from the rapid resolution of the disease accomplished by the immune system, which narrows the window of therapeutic opportunity. The immune response is also responsible for important clinical manifestations, including oedema and pain. The dual role of immune responses (protection, pathology) is well recognized in other infectious diseases. The addition of corticosteroids to antimicrobial agents has been associated with improvement in some of these diseases.

Evaluation of antiviral treatments for recurrent herpes simplex labialis in the dorsal cutaneous guinea pig model.

Recurrent herpes simplex labialis has proved to be a difficult disease to treat. Despite 25 years of clinical research with established antiviral substances, only small benefits from experimental therapies have been demonstrated. Progress has been slow, in part, because of the time-consuming nature of large, patient-initiated clinical trials. The dorsal cutaneous guinea pig model is a rapid and efficient means to identify topical antiviral formulations with clinical promise. The cumulative results of our studies with 19 different test treatments show that 8 were equal in efficacy to 5% acyclovir ointment, one was worse and ten were better. Two of the treatments found to be better than 5% acyclovir ointment have been studied clinically, with limited but encouraging results. Differences between the guinea pig model and the human illness mandate caution in predicting the degree of clinical efficacy from experimental outcomes. An effective and conservative use of the model is to optimize the topical formulation of a single antiviral substance.