Introduction to Cidofovir
Cidofovir is a potent antiviral medication administered intravenously, primarily to combat serious viral infections, especially in immunocompromised individuals. The FDA approved cidofovir in 1996 specifically for treating cytomegalovirus (CMV) retinitis in patients with AIDS. CMV retinitis is a serious eye infection that can cause blindness if not addressed. Cidofovir helps manage the symptoms without curing the infection.
Mechanism of Action
Cidofovir works by selectively inhibiting viral DNA synthesis. Unlike some other antivirals, it doesn't need activation by a viral enzyme. Host cell enzymes convert it to its active form, cidofovir diphosphate, which then competitively inhibits viral DNA polymerase, preventing viral replication. This mechanism is effective against many DNA viruses, including herpesviruses, adenovirus, polyomavirus, papillomavirus, and poxviruses.
Approved Indication: CMV Retinitis
Intravenous cidofovir's only FDA-approved use is for treating CMV retinitis in AIDS patients. Due to the risk of kidney damage, cidofovir requires prehydration with saline and co-administration with probenecid, which reduces cidofovir concentration in the kidneys.
Common Off-Label Uses
Cidofovir is widely used off-label for various other DNA virus infections, often when standard treatments are ineffective.
Cutaneous and Mucocutaneous Infections
Topical and intralesional cidofovir treats skin conditions like recalcitrant warts (verruca vulgaris), plantar warts, and anogenital warts (condyloma acuminata) caused by HPV, especially in immunocompromised patients. It is also effective for widespread or resistant molluscum contagiosum and acyclovir-resistant herpes simplex virus (HSV) infections.
Systemic Viral Infections
Intravenous cidofovir is used off-label for systemic infections in immunocompromised individuals, such as transplant recipients. This includes managing BK virus (BKV) associated hemorrhagic cystitis in hematopoietic stem cell transplant recipients and treating severe adenovirus infections. It is also considered for severe mpox infections due to its activity against poxviruses.
Comparison with Other Antivirals
For CMV retinitis, cidofovir is typically a second or third-line option due to its toxicity, with valganciclovir or ganciclovir being first-line therapies.
| Feature | Cidofovir | Ganciclovir | Foscarnet |
|---|---|---|---|
| Mechanism | Nucleotide analog; inhibits DNA polymerase | Nucleoside analog; requires viral kinase for activation | Non-nucleoside pyrophosphate analog; inhibits DNA polymerase |
| Administration | Administered intravenously | IV infusion, oral (valganciclovir), or ocular implant | IV infusion |
| Major Toxicity | Nephrotoxicity (kidney damage) | Myelosuppression (bone marrow suppression) | Nephrotoxicity, electrolyte imbalances |
| Resistance | Associated with mutations in the UL54 gene | Associated with mutations in UL97 and UL54 genes | Associated with mutations in the UL54 gene |
Cidofovir's advantages include less frequent dosing and effectiveness against some ganciclovir-resistant CMV. However, its significant kidney toxicity and the need for hydration and probenecid limit its routine use.
Conclusion
In summary, cidofovir's primary approved use is for treating CMV retinitis in AIDS patients, crucial for preventing vision loss. Its broad activity against DNA viruses also makes it a valuable off-label treatment for various infections, such as HPV-related skin conditions and life-threatening adenovirus and BK virus infections in transplant recipients. Despite its effectiveness, intravenous cidofovir carries a significant risk of kidney damage, requiring careful monitoring and a specific administration protocol with hydration and probenecid.
For more information on the use of cidofovir for cutaneous applications, you can review this article from the National Institutes of Health: Cutaneous Applications of the Antiviral Drug Cidofovir: A Review
