Two low doses of tenofovir protect newborn macaques against oral simian immunodeficiency virus infection

Simple affordable interventions are needed to reduce vertical human immunod eficiency virus (HIV) transmission in developing countries. The efficacy of 2 low doses (4 mg/ kg, subcutaneously) or 1 high dose (30 mg/kg, subcutane ously) of the reverse-transcriptase inhibitor 9[2-(phosphonomethoxy) propyl ] adenine (PMPA; tenofovir) to protect newborn macaques against simian immu nodeficiency virus (SIV) infection was investigated. Thirteen newborn macaq ues were inoculated orally with virulent SIVmac251. The 4 placebo-treated a nimals (group A) became persistently infected. Groups B and C (n=4 in each group) received 2 4- mg/kg doses of PMPA, either 4 h before and 20 h after (group B) or 1 and 25 h after SIV inoculation (group C). One animal (group D) received a single 30-mg/kg dose of PMPA 1 h after SIV inoculation. Despi te evidence of an initial transient infection, 3 group B animals, 2 group C animals, and the group D animal were SIV negative and seronegative at ages 19-23 months. Immune activation with recall antigens or pharmacologic immu nosuppression with corticosteroids failed to reactivate viral replication. These data suggest that 1 or 2 doses of PMPA may protect human newborns aga inst intrapartum HIV infection.