Administration of 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) for prevention of perinatal simian immunodeficiency virus infection in rhesus macaques.
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.
Van Rompay
K K
KK
California Regional Primate Research Center, University of California, Davis 95616, USA. kkvanrompay@ucdavis.edu
Marthas
M L
ML
Lifson
J D
JD
Berardi
C J
CJ
Vasquez
G M
GM
Agatep
E
E
Dehqanzada
Z A
ZA
Cundy
K C
KC
Bischofberger
N
N
Pedersen
N C
NC
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000097:blood; D002585:Cesarean Section; D002678:Chimera; D004334:Drug Administration Schedule; D005260:Female; D006678:HIV / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control; D006801:Humans; D008253:Macaca mulatta; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D011247:Pregnancy; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D000068698:Tenofovir; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D000914:Antibodies, Viral; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D012367:RNA, Viral; D000068698:Tenofovir; D000225:Adenine