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

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.

• Authors: K K Van Rompay, M L Marthas, J D Lifson, C J Berardi, G M Vasquez, E Agatep, Z A Dehqanzada, K C Cundy, N Bischofberger, N C Pedersen
• Journal: AIDS research and human retroviruses (AIDS Res Hum Retroviruses) Vol. 14 Issue 9 Pg. 761-73 (Jun 10 1998) ISSN: 0889-2229 [Print] United States
• PMID: 9643376 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-HIV Agents
• Antibodies, Viral
• Organophosphonates
• Organophosphorus Compounds
• RNA, Viral
• Tenofovir
• Adenine

Topics

• Adenine (administration & dosage, analogs & derivatives, blood, therapeutic use)
• Animals
• Animals, Newborn
• Anti-HIV Agents (administration & dosage, blood, therapeutic use)
• Antibodies, Viral (blood)
• Cesarean Section
• Chimera
• Drug Administration Schedule
• Female
• HIV (drug effects, genetics, immunology)
• HIV Infections (prevention & control)
• Humans
• Macaca mulatta
• Organophosphonates
• Organophosphorus Compounds (administration & dosage, blood, therapeutic use)
• Pregnancy
• RNA, Viral (blood)
• Simian Acquired Immunodeficiency Syndrome (drug therapy, immunology, prevention & control)
• Simian Immunodeficiency Virus (drug effects, genetics, immunology)
• Tenofovir
• Treatment Outcome