Cidofovir: clinical experience and future perspectives on an acyclic nucleoside phosphonate analog of cytosine in the treatment of refractory and premalignant HPV-associated anal lesions

Abstract

Background: Cidofovir, a nucleotide analog with antiviral activity against a broad range of DNA viruses including human papilloma viruses (HPV), is available off label to clinicians. Objective: To provide a better knowledge of pharmacology and effects when topically applied. Methods: After reviewing the chemistry, physiology, and animal studies, an overview of clinical studies is provided. Results/conclusions: Cidofovir, as a result of its antiviral and antiproliferative activity and its ability to induce apoptosis, can offer a solution for the treatment of severe recurrent HPV-induced lesions. It can also be used to attempt to treat dysplastic lesions and as an adjuvant treatment. The long-lasting antiviral activity allows infrequent dosing. As a rule, cidofovir applied on the skin is well tolerated, even in long-term treatment. The dose-limiting nephrotoxicity of the drug is not a concern in patients with a glomerular filtration rate within the normal range. Cidofovir has clearly influenced the landscape of refractory and dysplastic anogenital condylomata acuminata and its use has increased over the last decade. However, further controlled clinical trials are needed to assess the role of cidofovir and its derivatives.

Keywords::

• AIN
• antiviral activity
• apoptosis
• cidofovir
• condylomata acuminata
• HPMPC
• HPV-associated anogenital lesions
• nephrotoxicity
• phosphorylated metabolites