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

Koen K.A. Van Rompay, Marta Marthas, Jeffrey D. Lifson, Christopher J. Berardi, Gabriela M. Vasquez, Elmo Agatep, Zia A. Dehqanzada, Kenneth C. Cundy, Norbert Bischofberger, Niels C Pedersen

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67 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)761-773
Number of pages13
JournalAIDS Research and Human Retroviruses
Volume14
Issue number9
StatePublished - Jun 10 1998

ASJC Scopus subject areas

  • Immunology
  • Infectious Diseases
  • Virology

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    Van Rompay, K. K. A., Marthas, M., Lifson, J. D., Berardi, C. J., Vasquez, G. M., Agatep, E., Dehqanzada, Z. A., Cundy, K. C., Bischofberger, N., & Pedersen, N. C. (1998). Administration of 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) for prevention of perinatal simian immunodeficiency virus infection in rhesus macaques. AIDS Research and Human Retroviruses, 14(9), 761-773.