Viral phenotype in mother-to-child HIV-1 transmission and disease progression of vertically acquired HIV-1 infection.

Human immunodeficiency virus-1 (HIV-1) primary isolates differ in replicative capacity on peripheral blood mononuclear cells, tropism for primary monocyte-derived macrophages (MDM) and T-cell lines and syncytium-inducing (SI) capability on MT-2 cells in vitro. To assess the role of viral phenotype in mother-to-child HIV-1 transmission and the progression of vertically acquired HIV-1 infection, we studied 57 HIV-1-infected women at the time of delivery and 24 HIV-1-infected infants. Eight mothers transmitted the infection to their children. Primary isolates, obtained from 7 and 33 transmitting and non-transmitting mothers, respectively, differed in replicative capacity and SI activity, and no significant differences between the two groups were found regarding these viral properties. However, all primary isolates from transmitting mothers, but about half of those from non-transmitting mothers, were able to infect and replicate in MDM, regardless of their replicative capacity and/or SI activity; moreover, the monocyto-macrophage tropism of the maternal isolate correlated with an increased risk of transmission. Viral isolates from HIV-1-infected children were typed before 2 months of age; all but four showed a tropism for MDM, further supporting the notion that monocyto-macrophage tropic variants are selectively transmitted from mother to child and/or selectively replicated upon transmission. Clinical follow-up disclosed that 7/11 infants with a rapid/high replicating virus but none of the 17 with a slow replicating virus developed severe symptoms of disease and/or severe immunodepression by 1 year of age. By means of competitive RNA-polymerase chain reaction (PCR), a relationship was found between viral phenotype and dynamics of HIV-1 replication early in life in children who experienced different patterns of disease progression.