Cidofovir (Vistide)

Cidofovir (Vistide) is an antiviral drug, which is used to treat a range of different viruses. It comes either as a liquid for intravenous injection marketed under the trade name Vistide, or as a gel, which the manufacturer plans to market under the trade name Forvade.

Gilead has commenced trials of a pro-drug of cidofovir called GS 930 or cyclic HPMPC. The pro-drug is converted into cidofovir within the body.

Cidofovir was formerly known as HPMPC or by the codename GS-0504.

Intravenous cidofovir was approved in Europe and the United States for treating cytomegalovirus retinitis after two studies showed that it delayed the time to progression of the disease. One study enrolled people with newly diagnosed retinitis, while the other enrolled people with retinitis that had relapsed despite extensive treatment with other intravenous therapies.

For induction therapy, cidofovir is infused once per week for two weeks. Maintenance therapy consists of one infusion every two weeks. Because of this infrequent dosing schedule, patients do not need to have a catheter surgically implanted, as is required for other intravenous drugs for cytomegalovirus.

Probenecid (Benuryl / Probecid) tablets are given on the day of the infusion, to minimise the risk of kidney damage, the major side-effect from intravenous cidofovir. Kidney damage can be permanent or even fatal, so it is critical that proper precautions are observed. Cidofovir is always given in the clinic so that kidney function can be monitored. No other drugs that may damage the kidneys, including tenofovir (Viread), should be given with cidofovir or within a week before starting cidofovir, and it should never be used by people who already have impaired kidney function.

Cidofovir does not interact with any currently available protease inhibitors or non-nucleoside reverse transcriptase inhibitors (NNRTIs).

In May 1997, it was reported that intravenous cidofovir can cause inflammation of the eye in around 5% of recipients, usually within the first three months of treatment. Higher doses of cidofovir have been associated with hair loss in clinical studies.

Gilead has also developed a formulation of cidofovir that is injected directly into the eye. Trials in which cidofovir was injected into the eyes of people with cytomegalovirus retinitis found that pressure within the eye was reduced. Some people developed detached retinas, possibly because of reduced eye pressure. This therapy is not widely used.

The development of cytomegalovirus strains with reduced sensitivity to cidofovir has been noted among treated people. The risk of developing cidofovir resistance may be increased among people with prior exposure to anti-cytomegalovirus therapy, particularly ganciclovir (Cymevene).1 Cidofovir-resistant cytomegalovirus is expected to be cross-resistant to ganciclovir, but to remain susceptible to foscarnet (Foscavir).

Cidofovir gel is also being tested as a treatment for herpes simplex infections, warts and Molluscum contagiosum, following reports of improvement in a number of case studies.2 3 4 5 6 7 8 9 Preliminary studies suggest that the gel reduces the time to healing of herpes simplex lesions compared with placebo in both HIV-positive and HIV-negative people, although in May 1997 the United States Food and Drug Administration decided that the evidence was insufficient to allow cidofovir gel to be marketed.

There have been several reports of the use of intravenous cidofovir to try to treat progressive multifocal leukoencephalopathy (PML) but outcomes have been disappointing.10 However, combining cidofovir with antiretroviral therapy, particularly protease inhibitors, may lead to better response rates and survival.11 12 13 14 15 An American study is investigating the effectiveness of intravenous cidofovir for treating Kaposi’s sarcoma, after test-tube studies found that it was a potent inhibitor of human herpes virus-8.16

References

  1. Cherrington JM et al. In vitro antiviral susceptibilities of isolates from cytomegalovirus retinitis patients receiving first- or second-line cidofovir therapy: relationship to clinical outcome. J Infect Dis 78: 1821-1825, 1998
  2. Kopp T et al. Successful treatment of an aciclovir-resistant herpes simplex type 2 infection with cidofovir in an AIDS patient. Br J Dermatol 147: 134-138, 2002
  3. Calista D et al. Resolution of recalcitrant human papillomavirus gingival infection with topical cidofovir. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 90: 713-715, 2000
  4. Matteelli A et al. Efficacy and tolerability of topical 1% cidofovir cream for the treatment of external anogenital warts in HIV-infected persons. Sex Transm Dis 28: 343-346, 2001
  5. de Rossi SS et al. The management of oral human papillomavirus with topical cidofovir: a case report. Cutis 73: 191-193, 2004
  6. Hivnor C et al. Intravenous cidofovir for recalcitrant verruca vulgaris in the setting of HIV. Arch Dermatol 140: 13-14, 2004
  7. Martinelli C et al. Resolution of recurrent perianal condylomata acuminate by topical cidofovir in patients with HIV infection. J Eur Acad Dermatol Venereol 15: 568-569, 2001
  8. Calista D Topical cidofovir for severe cutaneous human papillomavirus and molluscum contagiosum infections in patients with HIV / AIDS. A pilot study. J Eur Acad Dermatol Venereol 14: 484-488, 2000
  9. Toro JR et al. Topical cidofovir. A novel treatment for recalcitrant molluscum contagiosum in children infected with human immunodeficiency virus 1. Arch Dermatol 136: 983-986, 2000
  10. Wyen C et al. Progressive multifocal leukencephalopathy in patients on highly active antiretroviral therapy: survival and risk factors for death. J Acquir Immune Defic Syndr 37: 1263-1268, 2004
  11. Portilla J et al. Progressive multifocal leukoencephalopathy treated with cidofovir in HIV-infected patients receiving highly active anti-retroviral therapy. J Infect 41: 182-184, 2000
  12. Razonable RR et al. Cidofovir treatment of progressive multifocal leukoencephalopathy in a patient receiving highly active antiretroviral therapy. Mayo Clin Proc 76: 1171-1175, 2001
  13. Robinson LG et al. Progressive multifocal leukoencephalopathy successfully treated with highly active antiretroviral therapy and cidofovir in an adolescent infected with perinatal human immunodeficiency virus (HIV). J Child Neurol 19: 35-38, 2004
  14. Roberts MT et al. Prolonged survival in AIDS-related progressive multifocal leucoencephalopathy following anti-retroviral therapy and cidofovir. Int J Antimicrob Agents 21: 347-349, 2003
  15. Garvey J et al. Progressive multifocal leukoencephalopathy: prolonged survival in patients treated with protease inhibitors and cidofovir: a case series. AIDS 20: 791-793, 2006
  16. Medveczky MM et al. In vitro antiviral sensitivity of the Kaposi's sarcoma-associated herpesvirus. AIDS 11: 1327-1332, 1997

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