VIRAL PHENOTYPE AND HOST-CELL SUSCEPTIBILITY TO HIV-1 INFECTION AS RISK-FACTORS FOR MOTHER-TO-CHILD HIV-1 TRANSMISSION

Objective: To investigate the role of maternal HIV-1 isolate phenotype and a child's cell susceptibility/resistance to viral infection in mo ther-to-child HIV-1 transmission. Patients and methods: Forty-nine wom en were studied at the time of delivery. Primary isolates, obtained by culturing patient peripheral blood mononuclear cells (PBMC) with PBMC from healthy donors, were characterized for tropism and syncytium-ind ucing capability in monocyte-derived macrophages (MDM), peripheral blo od lymphocytes (PBL), and in the MT-2 and MOLT-3 T-cell lines. Results : Seven women transmitted HIV-1 to their children. Primary isolates we re obtained from six and 28 transmitting and non-transmitting mothers, respectively. All primary isolates from transmitting mothers and thei r infants but only 50% of those from non-transmitting mothers replicat ed in MDM, regardless of their replication capacity in T-cell lines. P BL and MDM cells from six uninfected children were exposed to the corr esponding maternal isolates. Polymerase chain reaction analysis of HIV -1 DNA in cells and p24 antigen assay in culture supernatants disclose d that two PBL and five MDM cultures were resistant to viral infection ; two other PBL cultures, although HIV-l-infected, were negative for p 24 production. Depletion of CD8+ cells only partially restored product ive infection in CD4+ cell cultures. Moreover, all six PBL but only on e MDM cultures were productively infected by an isolate obtained from a transmitting mother, thus suggesting that MDM resistance to HIV-1 in fection is not viral isolate-restricted. Conclusions: Our findings str ongly suggest that mother-to-child HIV-1 transmission is influenced by both monocyte-macrophage tropism of the maternal isolate and suscepti bility of the child's target cells, in particular monocyte-macrophages , to HIV-1 infection.