Efficacy of the acyclic nucleoside phosphonates (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) against feline immunodeficiency virus

被引:20
|
作者
Hartmann, K
Kuffer, M
Balzarini, J
Naesens, L
Goldberg, M
Erfle, V
Goebel, FD
De Clercq, E
Jindrich, J
Holy, A
Bischofberger, N
Kraft, W
机构
[1] Univ Munich, Med Tierklin 1, D-80539 Munich, Germany
[2] Univ Munich, Inst Physiol, D-80539 Munich, Germany
[3] Univ Munich, Med Poliklin, D-80539 Munich, Germany
[4] Katholieke Univ Leuven, Rega Inst Med Res, B-3001 Louvain, Belgium
[5] GSF, Forschungszentrum Neuherberg, Oberschleissheim, Germany
[6] Acad Sci Czech Republ, Inst Organ Chem & Biochem, Prague, Czech Republic
[7] Gilead Sci Inc, Foster City, CA 94404 USA
关键词
FIV; acyclic nucleoside phosphonates; PMEA; FPMPA; AIDS; chemotherapy;
D O I
10.1097/00042560-199802010-00004
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The acyclic nucleoside phosphonates (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) were evaluated for their efficacy and side effects in a double-blind placebo-controlled trial using naturally occurring feline immunodeficiency virus (FIV)-infected cats. This natural retrovirus animal model is considered highly relevant for the pathogenesis and chemotherapy of HIV in humans. Both PMEA and FPMPA proved effective in ameliorating the clinical symptoms of FIV-infected cats, as measured by several clinical parameters including the incidence and severity of stomatitis, Karnofsky's score, immunologic parameters such as relative and absolute CD4(+) lymphocyte counts, and virologic parameters including proviral DNA levels in peripheral blood mononuclear cells (PBMC) of drug-treated animals, in contrast with PMEA, FPMPA showed no hematologic side effects at a dose that was 2.5-foId higher than PMEA.
引用
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页码:120 / 128
页数:9
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