DYNAMICS OF VIRAL REPLICATION IN INFANTS WITH VERTICALLY ACQUIRED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION

About one-third of vertically HIV-1 infected infants develop AIDS with in the first months of life; the remainder show slower disease progres sion. We investigated the relationship between the pattern of HIV-1 re plication early in life and disease outcome in eleven infected infants sequentially studied from birth. Viral load in cells and plasma was m easured by highly sensitive competitive PCR-based methods. Although al l infants showed an increase in the indices of viral replication withi n their first weeks of life, three distinct patterns emerged: (a) a ra pid increase in plasma viral RNA and cell-associated proviral DNA duri ng the first 4-6 wk, reaching high steady state levels (> 1,000 HIV-1 copies/10(5) PBMC and > 1,000,000 RNA copies/ml plasma) within 2-3 mo of age; (b) a similar initial rapid increase in viral load, followed b y a 2.5-50-fold decline in viral levels; (c) a significantly lower (> 10-fold) viral increase during the first 4-6 wk of age. All infants di splaying the first pattern developed early AIDS, while infants with sl ower clinical progression exhibited the second or third pattern. These findings demonstrate that the pattern of viral replication and cleara nce in the first 2-3 mo of life is strictly correlated with, and predi ctive of disease evolution in vertically infected infants.