1.Biochemical basis for increased susceptibility to Cidofovir of herpes simplex viruses with altered or deficient thymidine kinase activity.
Mendel DB1, Barkhimer DB, Chen MS. Antimicrob Agents Chemother. 1995 Sep;39(9):2120-2.
It has been observed that herpes simplex virus mutants with deficient or altered thymidine kinase activity are more susceptible to Cidofovir (CDV; 1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate) in tissue culture than are the parental strains. During infection of cells, the elevation of the dCTP pool by thymidine kinase mutant viruses is less than that induced by the wild-type virus. The competition between CDV diphosphate and dCTP at the viral polymerase is therefore changed in favor of CDV diphosphate, enhancing its activity.
2.Evaluation of Cidofovir (HPMPC, GS-504) against adenovirus type 5 infection in vitro and in a New Zealand rabbit ocular model.
de Oliveira CB1, Stevenson D, LaBree L, McDonnell PJ, Trousdale MD. Antiviral Res. 1996 Jul;31(3):165-72.
The antiviral inhibitory activity of Cidofovir [1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate, HPMPC, GS-504] against adenovirus type 5 (Ad5) in the New Zealand rabbit ocular replication model was evaluated. The 50% inhibitory dose (ID50) of Cidofovir was determined to be 4.7-9.5 micrograms/ml against four adenoviruses (two Ad5, Ad8 and Ad14) by plaque reduction assay in A549 cells. Twenty-four New Zealand rabbits received intrastromal inoculation and topical application of 2 x 10(6) plaque-forming units (PFU) per eye of Ad5 McEwen, a clinical isolate. Cidofovir was administered topically at three different concentrations twice per day, beginning 16 h postinoculation and continuing for 20 consecutive days. The inhibitory effects were determined by measuring suppression of virus replication and by observation of the clinical effects. Compared to the placebo group, the 1% and 0.5% Cidofovir-treated groups showed significantly reduced Ad5 ocular titers, fewer days of viral shedding and less severe subepithelial opacities (P = 0.
3.Iritis and hypotony after treatment with intravenous cidofovir for cytomegalovirus retinitis.
Davis JL1, Taskintuna I, Freeman WR, Weinberg DV, Feuer WJ, Leonard RE. Arch Ophthalmol. 1997 Jun;115(6):733-7.
OBJECTIVE: To describe intraocular inflammation due to treatment with intravenous cidofovir dihydrate for cytomegalovirus retinitis.
4.Intraocular pressure and aqueous humor dynamics in patients with AIDS treated with intravitreal cidofovir (HPMPC) for cytomegalovirus retinitis.
Banker AS1, Arevalo JF, Munguia D, Rahhal FM, Ishimoto B, Berry C, De Clercq E, Ochabski R, Taskintuna I, Freeman WR. Am J Ophthalmol. 1997 Aug;124(2):168-80.
PURPOSE: To evaluate the decrease in intraocular pressure associated with cidofovir (1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate; HPMPC) intravitreal injections.
