9-[2-(phosphonomethoxy)propyl]adenine therapy of established simian immunodeficiency virus infection in infant rhesus macaques

被引:94
作者
vanRompay, KKA
Cherrington, JM
Marthas, ML
Berardi, CJ
Mulato, AS
Spinner, A
Tarara, RP
Canfield, DR
Telm, S
Bischofberger, N
Pedersen, NC
机构
[1] UNIV CALIF DAVIS, DEPT VET MED & EPIDEMIOL, DAVIS, CA 95616 USA
[2] GILEAD SCI, FOSTER CITY, CA 94404 USA
关键词
D O I
10.1128/AAC.40.11.2586
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The long-term therapeutic and toxic effects of 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) were evaluated in simian immunodeficiency virus (SIV)-infected newborn rhesus macaques, Four untreated SIV-infected newborn macaques developed persistently high levels of viremia, and three of the four animals had rapidly fatal disease within 3 months, In contrast, long-term PMPA treatment of four newborn macaques starting 3 weeks after virus inoculation resulted in a rapid, pronounced, and persistent reduction of viremia in three of the four animals. Emergence of virus with fivefold-decreased susceptibility to PMPA occurred in all four PMPA-treated animals and was associated with the development of a lysine-to-arginine substitution at amino acid 65 (K65R mutation) and additional mutations in the reverse transcriptase; however, the clinical implications of this low-level drug resistance are unclear, No toxic side effects have been seen, and all PMPA-treated animals have remained disease-free for more than 13 months, Our data suggest that PMPA holds much promise for the treatment of human immunodeficiency virus-infected human infants and adults.
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收藏
页码:2586 / 2591
页数:6
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