Efficacy and tolerability of topical 1% cidofovir cream for the treatment of external anogenital warts in HIV-infected persons

BACKGROUND: Treatment options for anogenital warts in patients with HIV-1 are unsatisfactory because they fail to eradicate latent human papillomavirus. GOAL: To determine tolerability and efficacy of topical 1% cidofovir cream for the treatment of external anogenital warts in HIV-infected patients. STUDY DESIGN: A randomized, placebo-controlled, single-blind, crossover pilot study of either 1% cidofovir cream or placebo applied once daily 5 days a week for 2 weeks followed by 2 weeks of observation was performed. RESULTS: Six patients were randomized to 1% cidofovir cream and six to placebo. The latter patients eventually received 1% cidofovir cream. Thus, 12 treatment rounds of cidofovir were compared with six rounds of placebo. A reduction of more than 50% in the total wart area achieved by seven cidofovir treatments (58%), as compared with no placebo regimen (P = 0.02). Local reactions occurred in 10 of the 12 patients treated with cidofovir, as compared with 0 of the 6 subjects in the placebo group (P < 0.001). CONCLUSIONS: For the initial clearance of anogenital warts in HIV-infected patients, 1% cidofovir cream is significantly more effective than vehicle cream. Local mucosal erosion is a common side effect.     

Extensive oral condylomas treated by in situ cidofovir injection in an HIV patient

BACKGROUND: Human papillomavirus infections are difficult to treat and have a high rate of recurrence, especially in a setting of human immunodeficiency (HIV) infection. Moreover, there is no standard treatment for oral condylomas. PATIENTS AND METHODS: We report the partial success of in situ injections of cidofovir in an HIV patient, presenting extensive oral condylomas. The injections were well tolerated and the response was still present at one year while the immune status of the patient was unchanged. DISCUSSION: The efficacy of topical cidofovir against condyloma acuminata has been reported and the value of in situ cidofovir injections for the treatment of laryngeal papillomatosis is well established. This case report shows the need for further investigation of in situ cidofovir injections as an alternative treatment for human papillomavirus lesions that are difficult to treat because of both site and extension.     

Topical 1% cidofovir for the treatment of basal cell carcinoma

Cidofovir, a purine nucleotide analogue of deoxycytidine, is a drug effective against a wide number of DNA viruses. Recently, cidofovir has been supposed to exert antineoplastic activity, through the induction of apoptosis and the inhibition of angiogenesis. Four patients affected by basal cell carcinoma (BCC), who refused conventional surgery, were treated with a cream containing 1% cidofovir. The cream was applied every day for 10 days, then every other day for another 50 days. Histopathologic clearing was assessed with a skin biopsy performed on the previous lesional area 3 months after the end of treatment. All four patients achieved clinical healing of their lesion. Histological tumour regression was achieved in three patients. The treatment was well tolerated and the cosmetic results were excellent. No recurrences after an average 24-month follow up period were detected. The potential effectiveness of topical cidofovir for the non-surgical treatment of BCC have been shown. Nevertheless, appropriate clinical trials and prolonged follow-up periods are needed to confirm the efficacy and safety of topical cidofovir.     

Cidofovir inhibits growth of B16 melanoma cells in vivo

BACKGROUND: Cidofovir [(S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl) cytosine] is a commercially available nucleotide analogue that has antiviral activity against a broad range of DNA viruses and is effective against human cytomegalovirus infection. OBJECTIVES: We aimed to study the effect of cidofovir on growth of the highly aggressive melanoma tumour arising from mouse melanoma B16 cells grafted subcutaneously in C57B16/J mice. METHODS: Mice were treated daily with systemic cidofovir at several doses. In treated and control groups, tumour growth was measured using a calliper, and histological studies were performed. RESULTS: In untreated mice, massive invasive melanoma tumours were observed on day 5 after tumour cell grafting. Cidofovir treatment gave a dose-dependent reduction in tumour size. Tumour growth was inhibited by 62% at a dose of 37.5 mg kg(-1) three times weekly, as compared with control mice treated with saline alone. At 67 mg kg(-1) three times weekly, tumour growth was inhibited by 90%. Increasing the cidofovir dose to 50 or 100 mg kg(-1) daily resulted in a gradual increase in the antitumoral effect of the compound. In one experiment, cidofovir was administered at 100 mg kg(-1) five times weekly from the eighth day after the injection of tumour cells, when the tumour already had a volume of approximately 100 mm(3). In the treatment group, on the 14th day the tumour volume was approximately 200 mm(3), while in the control group it had increased to 750 mm(3). CONCLUSIONS: Although the mechanism is unknown, an antitumoral or antiangiogenic effect may be the reason for the activity of cidofovir in this model. In view of our findings, use of cidofovir should be further explored in the treatment of neoplastic diseases.     

The management of oral human papillomavirus with topical cidofovir: a case report

Cidofovir, a purine nucleotide analog of cytosine, has showed significant promise against a number of DNA viruses. In 1997, the US Food and Drug Administration approved the use of cidofovir intravenously in the treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. Recent studies and reports suggest that a topical form of cidofovir may be useful for treating viral cutaneous lesions recalcitrant to traditional treatments. We report the case of a 36-year-old man with human immunodeficiency virus (HIV) and recalcitrant human papillomavirus (HPV) lesions on the gingiva that were successfully treated with cidofovir gel 1%.     

Successful treatment of periungual warts with topical cidofovir

Periungual warts represent a treatment challenge because of its high recurrence rate and recalcitrance. These are benign lesions produced by the human papilloma virus (HPV) that often do not respond to habitual treatment. Cidofovir is a potent antiviral drug that acts inactivating viral DNA polymerase. Topical cidofovir for the treatment of HPV‐related cutaneous and mucous lesions is becoming increasingly common. Our aim was to assess the efficacy and safety of cidofovir cream for the treatment of viral periungual warts. We undertook a retrospective observational study of patients with periungual warts who received treatment with topical cidofovir between January 2010 and December 2013 at the Dermatology Service of the Hospital Costa del Sol, Marbella, Spain. Data were recorded about the rate of treatment response, the adverse effects and recurrences, as well as the characteristics of the patient cohort. We identified 41 patients who had received some previous treatment. The concentration of cidofovir was 3% in all cases, usually applied twice a day (in 37 of the 41 cases). A greater or lesser response was noted in 35 cases. There were six recurrences in the follow‐up period. Topical cidofovir seems to be a useful alternative for the therapeutic management of recalcitrant periungual common warts that fail to respond to usual treatment. Our experience with the use of this antiviral agent has been satisfactory, although in our opinion, it should be reserved for specific cases as its economical cost represents an important limitation.     

Cidofovir Intralesional Injection for Recalcitrant Common Warts: A Comparison with Sodium Tetradecyl Sulfate Intralesional Injection

BackgroundA novel treatment method is required for recalcitrant common warts.ObjectiveThis study aimed to compare the complete wart removal rate of cidofovir, a broad-spectrum antiviral agent, intralesional injection and sodium tetradecyl sulfate intralesional injection.MethodsThis retrospective study included 45 patients with recalcitrant common warts on the hands and/or feet, treated with cidofovir or sodium tetradecyl sulfate intralesional injection.ResultsThe treatment results were evaluated in three groups as follows: (1) failure - recalcitrant common warts remaining despite three or more injections, (2) success - free from warts for more than 6 months after the injection, and (3) recurrence. The cidofovir group (n=22) showed significantly higher treatment success rates than the sodium tetradecyl sulfate group (n=23) (90.91% vs. 26.09%, p<0.001). Two immunosuppressed patients in the cidofovir group had recurrent lesions after 2 months of being declared free from warts. Considering adverse effects, two patients in the cidofovir group complained of bulla formation with severe pain requiring narcotic painkillers.ConclusionAlthough this study has the limitations of a small sample size and retrospective design, patients with recalcitrant common warts showed a dramatic response to the treatment with cidofovir intralesional injection, with minimal complications.     

A review of topical and intralesional cidofovir

Cidofovir is a potent nucleoside analog antiviral drug approved for the treatment of cytomegalovirus (CMV) retinitis in patients with the Acquired Immune Deficiency Syndrome (AIDS). It is currently available only for intravenous infusion. Several small studies and case reports describe the successful use of cidofovir applied either topically or by intralesional injection in several virally induced cutaneous diseases. Available information demonstrates that cidofovir is a potent antiviral agent with activity against several DNA viruses that cause cutaneous disease when applied topically or administered by intralesional injection. No significant systemic side effects have been noted, although application site reactions are common and can occasionally be severe. The effective use of topical and intralesional cidofovir for the treatment of diseases of the skin caused by DNA viruses has been demonstrated in animals and a limited number of patients including those infected with human immunodeficiency virus (HIV). This article reviews the pharmacology of cidofovir and the utility of topical and intralesional cidofovir for the treatment of viral infections caused by human papillomavirus, herpesviruses (including acyclovir resistant strains), Kaposi's sarcoma-associated herpesvirus, molluscum contagiosum and monkeypox.     

Treatment of cutaneous human papilloma virus, poxvirus and herpes simplex virus infections with topical cidofovir in HIV positive patients

INTRODUCTION: Cidofovir (Vistide) is an antiviral marketed for the treatment of cytomegalovirus retinitis. Clinical efficacy has been reported with its broad antiviral spectrum that includes poxvirus, human papilloma virus and Herpes simplex. In immunodepressed patients, these infectious dermatoses are often recurrent and resistant. In an open study, we assessed the efficacy and clinical tolerance of cidofovir gel at 1 p. 100. PATIENTS AND METHODS: Twelve HIV-infected adults were included. Cidofovir gel at 1 p. 100 was applied directly on the lesions, once a day, for two weeks on the molluscum and condylomas, four weeks on the warts and one week on the chronic herpes. RESULTS: Four patients presented with warts and 3 of them with verruca plana. In 2 of the verruca plana patients, regression was complete although relapse was observed. Two failures were noted. Local application of the gel was not tolerated by one patient suffering from condylomas of the penis. Four patients presented with molluscum contagiosum. Two complete regressions with strong local reaction and two partial regressions were observed. The latter two patients exhibited severe immunodepression, one of them subsequently received infusions of cidofovir. Two women suffering from vulvar and perianal herpes resistant to acyclovir were treated for one week with cidofovir gel at 1 p. 100: no response was obtained. One of the patients stopped treatment because of local intolerance. A third, less immunodepressed, woman responded partially. COMMENTS: In HIV-positive patients, cidofovir in topical form appears to be indicated in extensive and confluent molluscum contagiosum. However, the effect occurs at the cost of local inflammation. The results are disappointing in papillomavirus lesions and in chronic acyclovir-resistant herpes ulcerations, efficacy is debatable.     

Topical Cidofovir for Refractory Verrucae in Children

Abstract: Warts are common and are a challenge to treat in some children, especially immunocompromised children and those who fail or cannot tolerate salicylic acid preparations and cryotherapy. Cidofovir, a nucleotide analogue with antiviral activity, has demonstrated promising results when compounded into a topical form to treat refractory warts. We present a retrospective institutional review of 12 children with refractory verrucae treated with 1% to 3% topical cidofovir compounded in an unscented moisturizing cream, applied every other day to daily. In our institutional series, only three patients (25%) demonstrated complete clearance of their verrucae. An additional four patients (33%) demonstrated partial clearance. Our experience using topical cidofovir has been less successful than previous institutional reviews, possibly because we used a lower concentration and less‐frequent dosing. More studies are needed to better characterize the efficacy, safety, and dosing of topical cidofovir for the treatment of refractory warts.     

Topical cidofovir for the treatment of recalcitrant viral warts and molluscum contagiosum in Jacobsen syndrome

Jacobsen syndrome is caused by a terminal deletion on the long arm of chromosome 11 and can be associated with immunodeficiency. Patients with Jacobsen syndrome can be predisposed to cutaneous viral infections that are difficult to treat. We report successful use of topical 1% cidofovir as treatment of recalcitrant verruca vulgaris in one patient and molluscum contagiosum in another patient with Jacobsen syndrome. Topical cidofovir appears to be a good treatment option in this cohort and should be considered early for treatment-resistant cutaneous viral infections.     

Efficacy of cidofovir in an HIV infected patient with an acyclovir and foscarnet resistant herpes simplex virus infection]

BACKGROUND: We report the case of an AIDS patient, whose persistant HSV2 ulceration was clinically and phenotypically resistant to acyclovir and foscarnet. Only five clinical isolates of simultaneous acyclovir and foscarnet resistance have been previously described. CASE REPORT: This patient, without history of opportunistic infection, was hospitalized for a recurrent scrotal ulceration resistant to several antiviral treatment such as acyclovir, valacyclovir or foscarnet. The CD4 count was stable at 150/mm(3) and the HIV viral load was below detection level. The last recurrence appeared rapidly under valacyclovir therapy which had been introduced after 65 days of foscarnet therapy. Thus, the patient received a new dose of foscarnet. After initial efficacy, the ulceration increased once again. HSV2 phenotypic determination was done and detected, at that time, a double resistance to acyclovir and foscarnet. Healing was obtained with intravenous cidofovir. DISCUSSION: Foscarnet and acyclovir resistance in an HSV2 isolate is rare. This report presents several particularities. First, whereas the earlier published patients with an acyclovir and foscarnet resistant strain were widely immunocompromised, this was not the case for our patient. Secondly, in contrast with most precedent observations in which acyclovir-resistant strain disappeared after foscarnet therapy, in our case the acyclovir resistant strain remained after foscarnet therapy. Finally, few reports concerned the clinical efficacy of cidofovir in HSV infection. In this case, we proved that intravenously cidofovir was highly and rapidly effective on acyclovir and foscarnet resistant strains.     

Intravenous cidofovir-induced resolution of disfiguring cutaneous human papillomavirus infection

Human papillomavirus infection is one of the most common and most distressing cutaneous diseases in patients with HIV infection. It is also a common, and often therapeutically challenging, infection in individuals who are immunologically competent. A wide range of therapeutic options exists for treating cutaneous human papillomavirus infections, but none is uniformly effective. In this report we describe a man with HIV-1 infection and disfiguring facial verruca vulgaris who demonstrated complete clinical response to intravenous cidofovir. Our report provides further support for the use of intravenous cidofovir as therapy for treatment-resistant and/or widespread cutaneous human papillomavirus infection.     

Resolution of recurrent perianal condylomata acuminata by topical cidofovir in patients with HIV infection

Anogenital condylomata acuminata are the most frequent clinical manifestation of genital human papillomavirus (HPV) infection. Association between human immunodeficiency virus (HIV) and HPV infections is frequent (range: 26-60% in males). Topical cidofovir (a nucleotide analogue antiviral drug active against a broad range of DNA viruses) is a potential treatment for anogenital warts in immunocompromised patients. We treated three HIV-infected patients with HPV perianal condylomas with topical 1% cidofovir in flexible collodion once a day for 2 weeks. The treatment resulted in complete clearance of the HPV lesions. The patients experienced mild transient erythema without any other side-effects. None of the patients relapsed during the 10-14-month follow-up period.     

Topical cidofovir for plantar warts

Plantar warts are a common reason for dermatological consultations and their treatment can occasionally be a challenge. Plantar warts are benign lesions produced by the human papillomavirus (HPV) that often fail to respond to habitual treatment. Cidofovir is a potent antiviral drug that acts competitively, inhibiting viral DNA polymerase. Our aim was to assess the efficacy and safety of cidofovir cream for the treatment of viral plantar warts. We undertook a retrospective observational study of patients with plantar warts who received treatment with topical cidofovir between July 2008 and July 2011 at the Dermatology Service of the Hospital Costa del Sol, Marbella, Spain. Data about the rate of treatment response, the adverse effects, and recurrences, as well as the characteristics of the patient cohort, were recorded. We identified 35 patients who had received some previous treatment. The usual concentration was 3% (in 33 of 35 cases), applied twice a day (in 31 of 35 cases). A greater or lesser response was noted in 28 cases. There were two recurrences. Topical cidofovir seems to be a useful alternative for the therapeutic management of recalcitrant plantar common warts that fail to respond to usual treatment.     

Topical cidofovir for severe cutaneous human papillomavirus and molluscum contagiosum infections in patients with HIV/AIDS. A pilot study

BACKGROUND: Cidofovir is a nucleoside analogue of deoxycytidine with a strong activity against several DNA viruses, including herpes, pox and human papilloma virus (HPV). MATERIAL AND METHODS: Fourteen acquired immunodeficiency syndrome patients, 10 with extensive HPV lesions and four with molluscum contagiosum (MC) infections, unresponsive to conventional therapies, were treated with a cream containing cidofovir 1%. All the subjects had been on treatment with highly active antiretroviral therapy for almost 1 year before starting the cream. Measured end-points of therapy were efficacy, tolerability, side-effects and freedom from recurrence. RESULTS: Thirteen of the 14 patients (92.8%) completed the therapy, one dropped out. These 13 eventually cleared their MC or warts, over varying periods of time. In nine, the lesions regressed 2 weeks from the end of the first cycle of therapy. Three patients needed two cycles and the last three consecutive courses of topical therapy before the cutaneous lesions healed. No recurrence was observed in nine patients over an average follow-up period of 24.1 months (range 12-30 months). Four patients had isolated relapses, which were successfully treated with simple curettage. SIDE-EFFECTS: All the patients experienced side-effects where they applied the cream. Inflammation, erosion and a burning sensation were the most frequent. Postinflammatory hyperpigmentation was observed in six cases, while two developed a transient alopecia on the beard area. No systemic side-effects or alteration of laboratory data were noted. CONCLUSION: Cidofovir appears to offer an effective therapeutic alternative option for lesions that are unresponsive to conventional methods. Appropriate clinical trials are required, however, to confirm the true efficacy and safety of topical cidofovir.     

Trichodysplasia Spinulosa in a 7‐Year‐Old Boy Managed Using Physical Extraction of Keratin Spicules

Trichodysplasia spinulosa (TS) is an uncommon skin disease characterized by a folliculocentric papular eruption and keratin spine formation, classically appearing on the central face and ears. It occurs in immunosuppressed patients and is linked to a viral etiology. Diagnostic tests including polymerase chain reaction (PCR) are available for detection of the TS‐associated polyomavirus. Effective treatment options include topical cidofovir and oral valganciclovir. We present a case diagnosed using PCR with skin scrapings and treated using physical extraction of the keratin spicules. Significant improvement was noted, suggesting a safe, cost‐effective treatment alternative.     

Acyclovir-resistant herpes exulcerans et persistens. Type II

Immunocompromised patients are developing in an increasing frequency acyclovir-resistant herpes simplex infections. Different treatment options need to be evaluated considering the possible side effects in regard to the patients' immunocompromised status. A 73-year-old woman with B-cell lymphatic leukemia with a secondary antibody deficiency syndrome and anemia suffered for one year with perianal ulcerations caused by acyclovir-resistant herpes simplex infection Type II. Based on previous reports about successful treatment of acyclovir-resistant herpes simplex infections with foscarnet, cidofovir or vidarabine and considering the different side effects of these drugs as well as the underlying diseases of the patient, we treated her with foscarnet intravenously. After 3 months the ulcers showed a nearly complete remission.     

Successful treatment of an aciclovir-resistant herpes simplex type 2 infection with cidofovir in an AIDS patient

Management of the increasing frequency of aciclovir-resistant herpes simplex virus (HSV) infections among immunocompromised human immunodeficiency virus-infected people demands additional treatment options. We report the case of a 38-year-old patient with acquired immune deficiency syndrome who suffered from a perianal butterfly ulcer, which was HSV-2 positive by polymerase chain reaction (PCR) analysis. The ulcer appeared during treatment of a cytomegalovirus (CMV) pneumonitis with ganciclovir. Despite additional valaciclovir therapy the lesion gradually progressed in size. Investigations including histology, PCR analysis and in situ hybridization of a biopsy from the growing ulcer margin confirmed the presence of HSV-2 infection. Importantly, HSV isolates from this specimen were resistant to aciclovir. Based on a report about the successful treatment of aciclovir-resistant HSV infection with cidofovir, our patient received this drug intravenously at a dose of 5 mg kg-1 body weight once weekly for a total of 3 weeks. Concomitant oral probenecid and prehydration were administered to minimize nephrotoxicity. Within 30 days of treatment the ulcer had almost (> 95%) completely healed. We conclude that cidofovir is a potent antiviral drug with a potential usefulness in the treatment of aciclovir-resistant HSV-2 infection. It deserves further investigation in clinical trials.     

Intravenous cidofovir for resistant cutaneous warts in a patient with psoriasis treated with monoclonal antibodies

Human papilloma virus is a common and often distressing cutaneous disease. It can be therapeutically challenging, especially in immunocompromised patients. We report a case of recalcitrant cutaneous warts that resolved with intravenous cidofovir treatment. The patient was immunocompromised secondary to monoclonal antibody therapy for psoriasis.