Administration of 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) for prevention of perinatal simian immunodeficiency virus infection in rhesus macaques

被引:64
作者
Van Rompay, KKA [1 ]
Marthas, ML
Lifson, JD
Berardi, CJ
Vasquez, GM
Agatep, E
Dehqanzada, ZA
Cundy, KC
Bischofberger, N
Pedersen, NC
机构
[1] Univ Calif Davis, Calif Reg Primate Res Ctr, Davis, CA 95616 USA
[2] NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, AIDS Vaccine Program,Lab Retroviral Pathogenesis, Frederick, MD 21702 USA
[3] Gilead Sci Inc, Foster City, CA 94404 USA
[4] Univ Calif Davis, Dept Vet Med & Epidemiol, Davis, CA 95616 USA
关键词
D O I
10.1089/aid.1998.14.761
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Simian immunodeficiency virus (SIV) infection of newborn macaques is a useful animal model to explore novel strategies to reduce perinatal human immunodeficiency virus (HIV) infection. The availability of two easily distinguishable virus isolates, SIVmac251 and the simian/human immunodeficiency virus chimera SHIV-SF33, allows tracing the source of infection following inoculation with both viruses by different routes. In the present study, we evaluated the efficacy of pre-and postinoculation treatment regimens with 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) to protect newborn macaques against simultaneous oral SIVmac251 and intravenous SHIV-SF33 inoculation. Untreated newborns became persistently infected following virus inoculation. When three pregnant macaques were given a single subcutaneous dose of PMPA 2 hr before cesarean section, their newborns became SIV-infected following SIV and SHIV inoculation shortly after birth. In contrast, when four newborn macaques were inoculated simultaneously with SIV and SHIV, and started immediately on PMPA treatment for 2 weeks, only one animal became persistently SIV-infected; the remaining three PMPA-treated newborns, however, had some evidence of an initial transient virus infection but were seronegative and healthy at 8 months of age. Our data demonstrate that PMPA treatment can reduce perinatal SIV infection and suggest that similar strategies may also be effective against HIV.
引用
收藏
页码:761 / 773
页数:13
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