Cellular replication of human immunodeficiency virus type 1 occurs in vaginal secretions

Most human immunodeficiency virus type 1 (HIV-1) transmission worldwide is the result of exposure to infectious virus in genital secretions. However, current vaccine candidates are based on virus isolates from blood. In this study, vaginal secretions from HIV-1-infected women were examined for evide nce of cellular viral replication that produced virus with properties diffe rent from that in blood. Multiply spliced HIV-1 messenger RNA, which is fou nd only in cells replicating virus, was detected in all vaginal lavage samp les tested. There was a strong correlation between the amounts of multiply spliced HIV-1 messenger RNA and of cell-free HIV-1 RNA in the lavage sample s. In addition, significant genotypic differences were found in cell-free v irus from matched blood plasma and vaginal secretions. Moreover, drug resis tance-associated mutations appeared in plasma virus several months before a ppearing in vaginal virus. These findings indicate that cellular replicatio n of HIV-1 occurs in vaginal secretions and can result in a virus populatio n with important differences from that in blood.