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 h uman immunodeficiency virus (HIV) infection. The availability of two e asily distinguishable virus isolates, SIVmac251 and the simian/human i mmunodeficiency 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 postinocul ation treatment regimens with 9-[2-(phosphonomethoxy)propyl]adenine (P MPA) to protect newborn macaques against simultaneous oral SIVmac251 a nd intravenous SHIV-SF33 inoculation. Untreated newborns became persis tently infected following virus inoculation. When three pregnant macaq ues were given a single subcutaneous dose of PMPA 2 hr before cesarean section, their newborns became SIV-infected following SIV and SHIV in oculation shortly after birth. In contrast, when four newborn macaques were inoculated simultaneously with SIV and SHIV, and started immedia tely on PMPA treatment for 2 weeks, only one animal became persistentl y SIV-infected; the remaining three PMPA-treated newborns, however, ha d some evidence of an initial transient virus infection but were seron egative 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.