A Phase I/II Study of the Safety and Efficacy of Topical 1-(S)-(3-Hydroxy-2-Phosphonylmethoxypropyl)Cytosine Dihydrate (Cidofovir; HPMPC) in the Treatment of Refractory Mucocutaneous Herpes Simplex Disease in Patients With AIDS

A Phase I/II Study of the Safety and Efficacy of Topical 1-(S)-(3-Hydroxy-2-Phosphonylmethoxypropyl)Cytosine Dihydrate (Cidofovir; HPMPC) in the Treatment of Refractory Mucocutaneous Herpes Simplex Disease in Patients With AIDS

To evaluate the safety and tolerance of topical cidofovir (HPMPC) therapy for refractory mucocutaneous herpes simplex virus disease in AIDS patients. To determine whether topical HPMPC therapy can induce re-epithelialization and healing of refractory mucocutaneous herpes simplex virus disease in AIDS patients. To evaluate the virologic effects of topical HPMPC therapy on herpes simplex virus shedding from refractory lesions.

Patients are randomized to receive topical therapy with placebo (vehicle alone) or HPMPC at either 0.3 or 1.0 percent once daily for 5 days. Patients are assessed to day 15; those with no significant toxicity are eligible to receive open-label topical HPMPC for up to 6 months.

Inclusion Criteria

Concurrent Medication:

Allowed:

• Antiretroviral therapy with AZT, ddI, ddC, or d4T.
• Oral trimethoprim/sulfamethoxazole.
• Dapsone.
• Atovaquone.
• Fluconazole.
• Rifabutin.
• Clarithromycin.

Patients must have:

• HIV seropositivity.
• Mucocutaneous herpes simplex virus (HSV) infection confirmed by previous viral culture and persisting without improvement despite at least 10 days of acyclovir at a minimum dose of 1 g/day (oral) or 15 mg/kg/day (intravenous).
• Measurable lesions.
• Consent of parent or guardian if less than 18 years of age.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

Active medical problems sufficient to hinder study compliance or assessment of treatment effect.

Concurrent Medication:

Excluded:

• Acyclovir.
• Immunomodulators (such as corticosteroids or interferons).
• Lymphocyte replacement therapy.
• Biologic response modifiers.
• Ganciclovir.
• Foscarnet.
• Vidarabine.
• Topical trifluridine.
• Other investigational drugs (except d4T).
• Amphotericin.
• Intravenous therapy for PCP.
• Chemotherapeutic agents.

Prior Medication:

Excluded within 14 days prior to study entry:

• Immunomodulators (such as corticosteroids or interferons).
• Lymphocyte replacement therapy.
• Biologic response modifiers.
• Ganciclovir.
• Foscarnet.
• Vidarabine.
• Topical trifluridine.
• Other investigational drugs with potential anti-HSV activity.
• Amphotericin.
• Intravenous therapy for PCP.

Excluded within 4 weeks prior to study entry:

• Chemotherapeutic agents.

Required:

• At least 10 days of prior acyclovir at a minimum dose of 1 g/day (oral) or 15 mg/kg/day (intravenous).

Substance abuse.