In infants the clinical course of HIV-1 infection is bimodal, differing considerably from that of adults. The effect of HIV-1 phenotypic features and plasma viral load on the clinical course of infection has been well established in adults, whereas in children it remains controversial. The aim of this study was to prospectively evaluate the effect of HIV-1 replication phenotypes during the first year of primary infection in the development of premature immunosuppression and early pediatric AIDS. In 62 vertically infected children replication rates of HIV-1 isolates from primary cultures and syncytium-inducing capability in MT-2 cell line were evaluated, together with plasma viral load. It was observed that rapid replication rate and syncytium-inducing phenotype accelerate the early onset of pediatric AIDS (p = 0.02 and p = 0.04, respectively). Rapid replication kinetics was the only significantly independent variable for early clinical outcome (risk ratio, 2.48; p = 0.02). Both viral properties contributed to rapid CD4+ T-cell depletion (p = 0.05 for rapid replication rate, p = 0.01 for syncytium-inducing viral phenotype). Plasma viral burden higher than 5.5 log(10) copies/mL after 6 mo of age tended to be associated with disease progression. In conclusion, initial HIV-1 biologic features in pediatric primary infection by vertical transmission may influence the progression to early immunosuppression and development of AIDS.