Cyclic HPMPC is safe and effective against systemic guinea pig cytomegalovirus infection in immune compromised animals

Cidofovir (HPMPC) is licensed for the treatment of cytomegalovirus (CMV) re tinitis in patients with AIDS but its use is limited by nephrotoxicity. We evaluated the safely and efficacy of 1-[((s)-2-hydroxy-2-oxo- 1,4,2-dioxaph osphorinan-5-yl)methyl]cytosine dihydrate (CHPMPC) the cyclic congener of c idofovir. Treatment was well tolerated both in normal guinea pigs and in an imals immune compromised with cyclophosphamide. Further, blood chemistry an alysis showed no adverse effects of CHPMPC treatment on kidney or liver fun ction. In efficacy studies in immune compromised guinea pigs challenged wit h a virulent salivary gland passaged guinea pig CMV, CHPMPC treatment signi ficantly reduced mortality resulting from disseminated virus infection. Qua ntitative culture showed that treatment also significantly reduced virus re plication in the liver and spleen, but not the lungs of infected animals. T he efficacy of CHPMPC combined with its improved safety profile appear to m ake it an attractive alternative to cidofovir for the treatment of herpesvi rus infections. Further evaluation is warranted. (C) 2000 Elsevier Science B.V. All rights reserved.