Early short-term 9-[2-(R)-(phosphonomethoxy)propyl]adenine treatment favorably alters the subsequent disease course in simian immunodeficiency virus-infected newborn rhesus macaques

Simian immunodeficiency virus (SIV) infection of newborn macaques is a usef ul animal model of human pediatric AIDS to study disease pathogenesis and t o develop intervention strategies aimed at delaying disease. In the present study, we demonstrate that very early events of infection greatly determin e the ultimate disease course, as short-term antiviral drug administration during the initial viremia stage significantly delayed the onset of AIDS. F ourteen newborn macaques were inoculated orally with uncloned, highly virul ent SIVmac251. The four untreated control animals showed persistently high virus levels and poor antiviral immune responses; they developed fatal immu nodeficiency within 15 weeks. In contrast, SIV-infected newborn macaques wh ich were started on 9-[2-(R)-(phosphonomethoxy)propyl] adenine (PMPA) treat ment at 5 days of age and continued for either 14 or 60 days showed reduced virus levels and enhanced antiviral immune responses. This short-term PMPA treatment did not induce detectable emergence of SIV mutants with reduced in vitro susceptibility to PMPA. Although viremia increased in most animals after PMPA treatment was withdrawn, all animals remained disease-free for at least 6 months. Our data suggest that short-term treatment with a potent antiviral drug regimen during the initial viremia will significantly prolo ng AIDS-free survival for HIV-infected infants and adults.