Dual infection with polyomavirus BK and acyclovir-resistant herpes simplex virus successfully treated with cidofovir in a bone marrow transplant recipient

A hematopoietic stem cell transplant recipient developed a mucosal herpes simplex virus-1 (HSV-1) infection while under acyclovir (ACV) treatment (HSV was later shown to be resistant to ACV). Concomitantly, the patient presented a hemorrhagic cystitis (HC) due to polyomavirus BK, for which intravenous cidofovir (CDV) was prescribed. The patient benefited from the broad-spectrum anti-DNA virus activity of CDV, and not only the HC resolved without signs of nephrotoxicity but also the HSV-1 lesions disappeared. This is the first report describing the effect of CDV on 2 simultaneous and unrelated DNA viral infections in an immunosuppressed transplant recipient. In addition, we describe here that this HSV-1 isolate possesses a unique phenotype and genotype.     

Intravesical cidofovir to treat BK virus‐associated hemorrhagic cystitis in children after hematopoietic stem cell transplantation

HC related to BK virus replication might be a severe complication following allogeneic HSCT. There are no clearly defined treatment guidelines in pediatric population. The data on the effectiveness of ICI to manage severe bleeding in children are very limited. We report our experience of intravesical cidofovir in four children, 6–15 yr of age, to manage grade III–IV BK virus‐associated HC. Three of four children had high CSA serum level prior to developing cystitis. Intravesical instillations of cidofovir resulted only in temporal relief of bleeding. After immune suppression was withdrawn or tapered, intravesical instillations of formalin solution had to be undertaken to abort severe bleeding. We concluded that intravesical cidofovir alone did not appear to be sufficiently effective in case of severe HC, necessitating complimentary procedures to stop macrohematuria.     

Effects of cidofovir on a novel cell-based test system for recurrent respiratory papillomatosis

BACKGROUND: Cidofovir has been reported to have activity against human papillomavirus (HPV) type 16, but no laboratory studies have been performed on HPV type 6, the main cause of recurrent respiratory papillomatosis (RRP). METHODS: HPV6b E6 cDNA-based C33A (non-HPV cervical carcinoma) cell line was produced. Two different doses of cidofovir were applied to parent C33A, C33AT6E6, and C33AT16E6 (HPV 16). Growth and flow cytometry analysis were performed. RESULTS: Polymerase chain reaction confirmed HPV6 E6 expression in C33AT6E6 cells. High-dose cidofovir was found to be toxic to all cell lines. Low-dose exposure was found to be toxic to C33AT16E6 cells at 3 days, whereas C33A and C33AT6E6 showed minimal toxicity at 6 days and earlier recovery following drug withdrawal. CONCLUSIONS: Cidofovir showed nonspecific toxicity against all 3 cell lines tested. HPV16 E6 expressing cells were more sensitive than parent or HPV6 E6 expressing cells. Cidofovir has no selective advantage for the RRP-related HPV6 E6 expressing cell line.     

The discovery of antiviral agents: ten different compounds, ten different stories

This review article, while autobiographical to some extent, describes the discovery of ten (classes of) antiviral compounds that have made (or just did not make) it to the market for the therapy of viral infections, but each in its own way influenced the landscape of our dealing with virus infections: (i) valaciclovir, (ii) BVDU, (iii) DHPA, (iv) cidofovir, (v) adefovir, (vi) tenofovir, (vii) stavudine, (viii) HEPT, (ix) TIBO, and (x) AMD3100. Successful drug development, as is certainly true for antiviral drugs and exemplified for the acyclic nucleoside phosphonates cidofovir, adefovir and tenofovir, requires patience and perseverance, and a close continuous and dedicated interaction between Chemistry, Biology/Medicine and Industry.     

Cidofovir treatment of human polyomavirus-associated acute haemorrhagic cystitis

Abstract: We report the case of an 18‐year‐old patient who received an allogeneic bone marrow transplant from an HLA‐identical unrelated donor for a Ph+ acute lymphoblastic leukemia, in his third complete remission. Cyclophosphamide and busulfan were used as conditioning treatment. Acute graft‐versus‐host disease developed on day +9, and the response to adequate treatment (steroids) was favourable. On day +45 the patient developed an acute severe haemorhragic cystitis, and BK polyomavirus was demonstrated in urine samples using electron microscopy and polymerase chain reaction. Urinary symptoms did not improve in spite of palliative treatment, but a response was evident after 2 weeks of cidofovir treatment.     

Treatment of cytomegalovirus infections beyond acute disease to improve human health

Human cytomegalovirus is a common virus that establishes latency and persistence after a primary infection in 50–90% of populations worldwide. In otherwise healthy persons, the infection is generally mild or asymptomatic, although it may cause mononucleosis, prolonged episodes of fever, and hepatitis. However, in AIDS patients and transplant recipients who are immunosuppressed, severe, life-threatening infections may develop. CMV is also the most common congenital infection and may cause birth defects and deafness. Emerging evidence shows a high prevalence of this virus in patients with chronic inflammatory diseases or tumours of different origin, such as breast, colon, and prostate cancer, neuroblastoma, medulloblastoma, and glioblastoma. Several drugs are available to treat CMV infections. This review will highlight the possibility of using anti-CMV therapy to improve outcome not only in patients with acute CMV infections but also in patients with inflammatory diseases and cancer.     

Squamous cell carcinoma associated with intralesional injection of cidofovir for recurrent respiratory papillomatosis

Recurrent respiratory papillomatosis is a common neoplasm of the larynx that may lead to severe, recurrent lesions. Intralesional injection of cidofovir has shown promise as an adjuvant therapy. There is concern for possible malignant transformation with its use but, to our knowledge, this has not been documented in the literature. We report a case of invasive squamous cell cancer arising from squamous papilloma in a patient treated with multiple injections of cidofovir. Although causation is not shown, we believe the association presented is a valuable addition to the literature and an important consideration in the use of cidofovir. Laryngoscope, 119:567–570, 2009