Concordance between the CC chemokine receptor 5 genetic determinants that alter risks of transmission and disease progression in children exposed perinatally to human immunodeficiency virus

If CC chemokine receptor 5 (CCR5)-dependent mechanisms at the time of initi al virus exposure are important determinants of virus entry and disease out come, then the polymorphisms in CCR5 that influence risk of transmission an d disease progression should be similar; this hypothesis was tested in a co hort of 649 Argentinean children exposed perinatally to human immunodeficie ncy virus type 1 (HIV-1). Two lines of evidence support this hypothesis. Fi rst, CCR5 haplotype pairs associated with enhanced risk of transmission wer e the chief predictors of a faster disease course. Second, some of the hapl otype pairs associated with altered rates of transmission and disease progr ession in children were similar to those that we previously found influence d outcome in European American adults. This concordance suggests that CCR5 haplotypes may serve as genetic rheostats that influence events occurring s hortly after initial virus exposure, dictating not only virus entry but, by extension, also the extent of early viral replication.