Vulvar therapies
Miranda A. Farage, Howard I. Maibach in The Vulva, 2017
The antiviral cidofovir has been reported to be effective in limited case series. One study has shown a 65% response rate (90). Typically, this drug is used as a 1% gel applied for 5 days straight, followed by 1 week rest, for up to six cycles. Four hours after application, the area must be washed. In a placebo-controlled trial, 47% of cidofovir-treated patient achieved complete remission compared with none of the placebo controls (100). Another placebo-controlled trial in HIV-positive patients showed similar results (101). In HIV-infected patients, one randomized (but not placebo-controlled) study showed the efficacy of cidofovir combined with electrosurgery, with a significant reduction of recurrence in patients treated with both cidofovir and electrosurgery in comparison to patients treated by surgery alone (102). These data are based on few subjects and further investigation is necessary; however, cidofovir remains a promising option for the future.
Cytomegalovirus Retinitis
Glenn J. Jaffe, Paul Ashton, P. Andrew Pearson in Intraocular Drug Delivery, 2006
Cidofovir is an antiviral nucleotide analogue with significant activity against CMV and other herpesviruses. Cidofovir has a long intracellular half-life which allows for a prolonged interval (2 weeks) between intravenous maintenance doses, in contrast to daily administered intravenous ganciclovir and foscarnet (70). The efficacy of intravenous cidofovir has been demonstrated in AIDS patients with untreated CMV retinitis and with previously treated, relapsing CMV retinitis (71,72). Indirect comparisons of clinical trial data suggest that intravenous cidofovir appears to have similar efficacy to intravenous ganciclovir or foscarnet in delaying progression of CMV retinitis. Intravenous cidofovir is less invasive, more convenient due to its prolonged dosage interval and an indwelling catheter is not required. The major treatment-limiting side effect is potentially irreversible nephrotoxicity; thus, renal function tests, hydration, and simultaneous administration of probenecid are required. A relatively high rate of anterior uveitis, up to 40%, has been reported and a small number of patients have developed hypotony with intravenous cidofovir (73). These ocular complications were even more prevalent with trials of intravitreal cidofovir administration and have percluded its administration by this route (74).
Recurrent respiratory papillomatosis
Declan Costello, Guri Sandhu in Practical Laryngology, 2015
Cidofovir has been licensed for use in cytomegalovirus (CMV) retinitis of AIDS as a second-line treatment. CMV has its own viral DNA polymerase, which more avidly incorporates cidofovir than human DNA polymerase. However, HPV does not have its own viral DNA polymerase and sabotages the function of the human host polymerase. The mechanism of action of cidofovir in RRP is related to the kinetics of DNA synthesis: if the HPV-infected papillomas are growing more rapidly than normal mucosal cells infected with dormant HPV, cidofovir will have more potential for incorporation into the papilloma. There is evidence that cidofovir is useful against high-risk HPV-related tumours and it was probably this that prompted the use of cidofovir for RRP. Direct comparison of cidofovir effects of closely related cell lines transfected with HPV-6 and HPV-16 genes demonstrate a smaller effect on the former cell line.35
Drug-induced Uveitis in HIV Patients with Ocular Opportunistic Infections
Published in Ocular Immunology and Inflammation, 2020
Ilaria Testi, Aniruddha Agarwal, Rupesh Agrawal, Sarakshi Mahajan, Alessandro Marchese, Elisabetta Miserocchi, Vishali Gupta
CMV retinitis is the most common opportunistic ocular infection among patients with AIDS and CD4 + T cells <50 cells/mm3456-8 In the developed world, the incidence of CMV retinitis has decreased by 80-90% due to the availability of CART; however, the disease still has a prevalence of more than 25% in HIV-infected patients.7–9 Three drugs approved by the United States Food and Drug Administration (FDA) are available for the treatment of CMV retinitis: ganciclovir (and the pro-drug valganciclovir), foscarnet and cidofovir.10 Standard therapies include parenteral ganciclovir or foscarnet, oral ganciclovir or valganciclovir and intravitreal injections of these agents. Cidofovir is usually administered, either intravenously or locally, in patients who are intolerant or resistant to the other antiviral drugs.10,11
A comprehensive review of treatment options for recalcitrant nongenital cutaneous warts
Published in Journal of Dermatological Treatment, 2022
Kanchana Leerunyakul, Sasima Thammarucha, Poonkiat Suchonwanit, Suthinee Rutnin
Cidofovir is a potent nucleotide analog that functions through viral DNA polymerase inhibition. A retrospective review showed demonstrated that 98% of 280 resistant lesions disappeared after an average of 2–3 injections of 15 mg/mL of intralesional cidofovir monthly. Only local side effects (pain, burning sensation, erythema, and itch) were observed (128). The topical application of cidofovir cream also showed promising outcomes (129–133). A retrospective observational study of 126 patients in which 97.6% were resistant to previous therapies demonstrated a complete response in 53.2% of patients. Application under occlusion had better outcomes (81.2% vs. 49%). The 3% concentration showed a slightly better response (53.8% vs. 42.9%), while the frequency of application did not add an advantage (129). The side effects were similar to intralesional injection.
The discovery of novel antivirals for the treatment of mpox: is drug repurposing the answer?
Published in Expert Opinion on Drug Discovery, 2023
Ahmed A. Ezat, Jameel M. Abduljalil, Ahmed M. Elghareib, Ahmed Samir, Abdo A. Elfiky
N-methanocarbathymidine is a thymidine analog that depends on viral thymidine kinase to be activated (triphosphate form) [48]. N-methanocarbathymidine was discovered as an antiviral agent against herpes viruses; however, later work reported its antiviral activity against the vaccinia virus and cowpox virus in mice models if taken twice daily at 100–500 mg/kg of body weight [48]. Similarly, KAY-2-41 (1́-carbon-substituted 4́-thiothymidine derivative) was found to be more active than cidofovir (but lower than brincidofovir or tecovirimat) against the vaccinia virus, cowpox virus, and camelpox virus when tested in vitro [49]. It also retained its antiviral activity on cidofovir-resistant strains. Furthermore, mice models challenged with the vaccinia virus through the respiratory route survived the lethal infection when KAY-2-41 was intraperitoneally administered at a dose of 50 mg/kg once daily [49].
Related Knowledge Centers
- Antiviral Drug
- Cytomegalovirus
- Herpes Simplex Virus
- Progressive Multifocal Leukoencephalopathy
- Smallpox
- Topical Medication
- Injection
- Retinitis
- HIV/AIDS
- Aciclovir