Biological correlates of HIV-1 heterosexual transmission

Objectives: To study the role of HIV-1 biological phenotype, viral load and neutralizing antibodies in male-to-female heterosexual transmission of HIV-1. Methods: Seven transmitting and seven non-transmitting HIV-l-seropositive heterosexual male index cases were included in the present study. All couples had engaged in unprotected sex for a period of over 1 year. Transmission was defined by the seroconversion of the female sexual partner. Virus isolates were tested in MT-2 cells for replication and syncytia induction. HIV-1 RNA plasma load was measured by the branched DNA technique. Serum neutralizing activity to primary HIV-1 isolates was tested by using peripheral blood mononuclear cells (PBMC) as target cells. Results: Non-transmitting index cases had a lower HIV-1 RNA concentration in plasma than transmitting index cases. Non-transmitting index cases also tended to have serum neutralizing activity with broad specificity and to have viruses with low replicative capacity, as characterized by 50% infectious dose titres in PBMC and by the lack of MT-2 tropism. Conclusions: The results indicate that plasma viral-RNA load is a marker for transmission. Moreover, an interplay between the host immune response and viral replication may modulate the level of viral load and thereby influence HIV-1 transmission.