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Antiviral therapeutics for viral infections of the central nervous system
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
In addition to its approved use of treatment of AIDS-associated CMV retinitis, cidofovir has a broad spectrum of activity, and can be used against acyclovir- and ganciclovir-resistant strains of HSV and CMV, respectively. Its potential therapeutic role has been tested in other clinical situations as well. Case reports also suggest that cidofovir may be beneficial in the treatment of BK virus nephritis in renal transplant patients [50,51]. Cidofovir was used to treat progressive multifocal leukoencephalopathy caused by JC virus in patients with AIDS, but failed to prove efficacious [52,53]. Importantly, cidofovir does not cross the blood brain barrier well and is not recommended for the treatment of CNS disease.
Implantation of a sustained-release ganciclovir implant
Published in A Peyman MD Gholam, A Meffert MD Stephen, D Conway MD FACS Mandi, Chiasson Trisha, Vitreoretinal Surgical Techniques, 2019
April Harris, Stephen A Meffert, Mandi D Conway
The ganciclovir implant has demonstrated the longest median time (226 days) to progression of CMV retinitis of all FDA-approved treatments for this disease. Left untreated, the median time to progression of CMV retinitis is 15 days.18 Administration of intravenous ganciclovir, foscarnet, or low-dose cidofovir delays the median time to progression to 47, 53, or 64 days, respectively.4,5 The median time to progression has not yet been successfully delineated in patients receiving high-dose cidofovir, but comparison with ganciclovir implants might be complicated by recent advances in AIDS therapy that elevate CD4 counts. The median time to progression with oral ganciclovir is 64 days, which is similar to intravenous therapy.29
Juvenile-Onset Recurrent Respiratory Papillomatosis
Published in John C Watkinson, Raymond W Clarke, Christopher P Aldren, Doris-Eva Bamiou, Raymond W Clarke, Richard M Irving, Haytham Kubba, Shakeel R Saeed, Paediatrics, The Ear, Skull Base, 2018
Based on their animal work, Chhetri and Shapiro45 have proposed a schedule for treatment of JORRP based on intralesional injections of cidofovir at a concentration of 1 mg/mL. Injections were given at 2-weekly intervals for four treatments and then the interval between treatments extended by 1 week after each and every subsequent treatment. Concomitant laser surgery was reserved for bulky lesions. Five patients were treated with this schedule with a mean follow-up time of 66 weeks. The mean papilloma stage decreased from 9.2 at initial presentation to 3.4 within 2 weeks of the first injection, and continued to decrease for the remainder of the follow-up period. After 9 weeks of treatment, no patients required further laser surgery. The authors counsel caution that the potential long-term carcinogenic effects of cidofovir are unknown and a ‘response’ may be related to the natural history of the disease.46
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].
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.
HIV-induced Retinitis
Published in Ocular Immunology and Inflammation, 2020
Juliana Wons, John Kempen, Justus G. Garweg
Alternative systemic drugs for induction and maintenance in cases of resistance to ganciclovir are foscarnet and cidofovir.40 Cidofovir and foscarnet have shown substantial nephrotoxicity requiring dose adaptation in more than 30% of cases and quite frequently treatment interruption.13 Compared to foscarnet, which needs to be taken twice daily, cidofovir has the advantage of a dosing interval of several weeks although the latter can lead to severe iritis and ocular hypotony.4,13 Cidofovir should be given in parallel with saline hydration and high-dose probenecid; the presence of even trace amounts of urinary protein must be excluded before each cidofovir dose as the drug’s long intracellular half-life may otherwise lead to progressive renal failure.64 In vision-threatening conditions such as fovea-sparing macular involvement, intravitreal ganciclovir or foscarnet may be added to enhance the effect of intravenous treatment. If retinitis extension cannot be controlled within a few days of systemic therapy, and if full-dose systemic therapy is not supported due to side effects, intravitreal injections of ganciclovir, foscarnet, or cidofovir have also been considered as an adjunct. Since systemic anti-CMV therapy treats or prevents possible affections of other organs and decreases mortality in the window before immune recovery occurs, it is preferred as the primary modality of treatment.2,65