Lack of autologous neutralizing antibody to human immunodeficiency virus type 1 (HIV-1) and macrophage tropism are associated with mother-to-infant transmission

Abstract

To investigate factors that affect mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1), autologous neutralizing antibody, viral load, and viral tropism were evaluated in 28 pregnant women infected with HIV-1, of whom 8 were transmitters and 20 nontransmitters. One (12%) of 8 transmitters versus 11 (55%) of 20 nontransmitters had autologous neutralizing antibody (P = .04). Plasma levels of HIV-1 RNA and infectious HIV1 titers (mean τ SD) in peripheral blood mononuclear cells (PBMC) at delivery did not differ significantly between transmitters and nontransmitters (24,266 τ 10,101 vs. 31,589 τ 9128 copies/mL and 29 τ 12 vs. 42 τ 17 infected cells per 106 PBMC, respectively). However, only transmitters (4 [50%] of 8) were HIV p24 antigen positive. The ability of HIV-1 strains to induce syncytium did not differ between groups (P = .6); however, only non-syncytium-inducing isolates were transmitted. Isolates from 4 (80%) of 5 transmitters versus 2 (18%) of 12 nontransmitters (P = .03) demonstrated increasing replication in macrophages. Thus, lack of autologous neutralizing antibody and increased replication in macrophages were significantly associated with mother-to-infant transmission. In addition, autologous neutralizing antibody was associated with reduced viral load.