Topical cidofovir for severe warts in a patient affected by AIDS and Hodgkin's lymphoma

Introduction

Human papillomavirus (HPV)-derived cutaneous warts are common, benign, usually self-limited lesions with a preference for the hands and feet. In patients suffering from haematological malignancies and HIV infection, the HPV infections are difficult to resolve due to their compromised and suppressed immune systems. ¹ In these clinical conditions, HPV-induced lesions tend to be more aggressive and may be particularly difficult to treat. We present to our knowledge the first case of severe cutaneous warts in a patient affected by AIDS and Hodgkin's lymphoma successfully treated with topical cidofovir (CDV).

Case Report

A 42-year-old Caucasian male, in May 2007 presented an 8–10-year history of multiple, progressively enlarging verrucous papules of the hands and the feet indicating a clinical diagnosis of verruca vulgaris. The patient was HIV-1 infected prior to 1984. He had a history of advanced immunodepression and hepatitis C virus-related hepatitis. AIDS-defining diseases (cerebral toxoplasmosis and cytomegalovirus retinitis) were diagnosed in 1996. In September 2001, CD4+ T-lymphocyte count fell to 0/mm³, plasma HIV-1 RNA was 330.000 copies/mL and the patient had received multiple antiretroviral regimens without adequate adherence. In August 2003, CD4 cell count was 24/mm³ and HIV-1 RNA was 2829 copies/mL. Since September 2003, the patient takes regularly antiretroviral therapy (ART), with stavudine, tenofovir, atazanavir boosted by ritonavir and enfuvirtide. Enfuvirtide was administered for a period of 12 months. At follow-up HIV-1 RNA results always at undetectable levels (<40 copies/mL) and CD4 cell count had progressively increased (from March 2004 to June 2005 CD4 cell count range was between 100 and 200/mm³). In 2005, he developed Hodgkin's lymphoma (stage IV B) and subsequently was treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, which resulted in complete haematological remission, since November 2006. In May of 2007 CD4 cell count was 239/mL (23%). Despite this increase of CD4 cells, the remission of haematological disease and a variety of therapeutic modalities administered, including liquid nitrogen cryosurgery, topical tretinoin solution, podophyllin and multiple surgical excisions, these verruca vulgaris lesions were not resolved. These treatments were all clinically ineffective. A biopsy of the lesions revealed a typical HPV infection with no evidence of cell dysplasia and by HPV INNO-LiPA genotyping test (Innogenetics, Ghent, Belgium) HPV genotype 16 and 66 was identified. Given the failure of previous treatments, the patient was treated with a cream containing 1% of CDV (Vistide vial) and a combination vehicle (cold cream), prepared in the pharmacy of the hospital. The patient was informed that the drug was not approved for this indication and he gave the consent for the treatment. The cream was applied in occlusive topical application twice daily, five days for a week in two weeks. In the first week, a reduction in the size of the lesions was observed with no apparent negative side-effects. At the completion of the treatment period of twoweeks, all lesions had completely resolved with the exception of one remaining lesion, which was subsequently removed by a single surgical excision. A follow-up examination six months later showed no reoccurrence of lesions on his hands or feet. Figure 1 shows the hands and the feet of the patients before and after CDV therapy.

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Figure 1

(a) Hands before cidofovir therapy; (b) Hands after two weeks of cidofovir therapy; (c) Foot before cidofovir therapy; (d) Foot after two weeks of cidofovir therapy

Discussion

In advanced HIV disease, especially when haematological malignancies are present, cutaneous warts may be difficult to treat. In some patients, the HPV lesions may improve following ART treatments leading to a decrease in HIV viral load (VL) and increases in CD4 cell count. However, this was not observed in our case study. The patient did not have any improvement in his HPV lesions even after the ART treatment resulted in stable decrease of HIV VL (<40 copies/mL) and increase of CD4 cell count.

HPV-induced skin lesions in HIV-positive individuals have been reported to be successfully treated by topical CDV administration,^2,3 even if appropriate clinical studies to support this approach are scanty. CDV is a broad-spectrum antiviral agent with activity against all human herpes viruses and HPV. ⁴ In our case topical CDV therapy results effective and safe. Differently from other approved therapy the advantage of this drug is the specific antiviral effect on HPV. Previous studies have used CDV intravenously as an effective treatment against HPV-derived lesions. However, the drug is expensive and the systemic use is limited by adverse effects, including nephrotoxicity, neutropenia, metabolic acidosis and possible teratogenicity.^5–7 Although a CDV topical cream is not available commercially, in selected cases may be easily prepared by the hospital pharmacy. Here, we first describe a patient affected by AIDS and Hodgkin's lymphoma successfully treated with topical CDV. The treatment of HPV-associated skin lesions with the local application of CDV seems to be a promising strategy in severely immunocompromised patients in whom classical regimens have failed.