Pilot Study of Topical Trifluridine for the Treatment of Acyclovir-Resistant Mucocutaneous Herpes Simplex Disease in Patients with AIDS (ACTG 172)

Abstract

Twenty-six AIDS patients were enrolled in an open label pilot study to evaluate the efficacy and toxicity of topical 1 percent ophthalmic trifluridine solution for the treatment of chronic mucocutaneous herpes simplex virus disease unresponsive to at least 10 days of acyclovir therapy. Susceptibility testing to acyclovir, trifluridine, and foscarnet was determined by plaque reduction assay. Twenty-four patients were evaluable for efficacy and 25 for toxicity analyses. Seven patients (29 percent) had complete healing of lesions. The overall estimated median time to complete healing was 7.1 weeks. An additional seven patients had > or = 50 percent reduction in lesion area. The overall estimated median time to 50 percent healing was 2.4 weeks. Ten (42 percent) patients discontinued treatment for reasons other than primary treatment failure and seven (29 percent) for failure to respond to therapy. Baseline patient characteristics associated with greater reduction in lesion area included higher Karnofsky score (p = 0.05), fewer lesions (p = 0.07), smaller lesion area (p = 0.11), and trifluridine susceptibility (p = 0.07). Eight (33 percent) patients developed new lesions outside of the treatment area while on study, reflecting the local nature of this therapy. No dose-limiting toxicity attributable to trifluridine was reported. Given the limited options for the treatment of acyclovir-resistant herpes simplex disease, topical trifluridine may be a useful alternative in selected patients.

Viral infections in atopic dermatitis Pathogenic aspects and clinical management

“…57 Trifluorothymidine 1% eye drops 7 to 9 times per day, as well as 3% acyclovir ointment 3 to 5 times per day, are typically instituted prophylactically, as well as in patients with established epithelial keratitis. 58,59 Topical idoxuridine and brivudin, which is not licensed yet, also demonstrate good activity in the treatment of herpetic keratitis. 60,61 Future treatment techniques for HSV infection.…”

Antiviral Therapy of Herpes simplex and Varicella-zoster Virus Infections

“…In such cases, the development of resistance of host cells to the antiviral drug during long-lasting expo sure should be considered [105]. In patients with mucocu taneous lesions caused by aciclovir-resistant strains, topi cal treatment with trifluridine or foscamet may be an alternative therapy [106,107], Topical cidofovir has also been used successfully for the treatment of persistent mucocutaneous HSV infections that were refractory to therapy w'ith aciclocir and/or foscamet [108], Since most severe diseases are caused by reactivation of latent herpesviruses, prophylactic use of antiviral drug in immunosuppressed patients is indicated [109]. Almost complete suppression of latent HSV and VZV infections during intravenous or oral prophylaxis with aciclovir has been demonstrated in most patients at increased risk of recurrence because of bone marrow transplantation, ra diotherapy or cytotoxic chemotherapy.…”

Resistance of Herpes Simplex Virus Infections to Nucleoside Analogues in HIV‐Infected Patients

“…A much more common problem is that of recurrences of HSV at oral or genital sites. These outbreaks are often more frequent, more extensive and necrotic, of longer duration, atypical in appearance, and complicated by oral mucositis or esophagitis [2,5,7,[10][11][12][13]. The more severe the immunosuppression, the more likely the episode is to be clinically complex.…”