Features of HIV-1 that could influence maternal-child transmission

Abstract

Objective: To evaluate the biological and serological properties of the human immunodeficiency virus type 1 (HIV-1) for factors potentially involved in the mother-to-child transmission of HIV-1.

Design: Isolates of HIV-1 were recovered from the blood of 12 of 44 nontransmitting mothers and six of eight transmitting mothers and their corresponding infants. These 24 HIV-1 isolates were compared for their biological and immunologic properties to discern any parameters that correlate with vertical transmission of HIV-1.

Main outcome measures: Replication capabilities of the above-mentioned HIV-1 isolates in human peripheral blood mononuclear cells (PBMCs), human macrophages, and various T-cell lines and the susceptibilities of the viruses to neutralization or enhancement by anti-HIV-1 antibodies in autologous serum samples from mothers and infants.

Setting: San Francisco Bay Area, California.

Participants: A cohort of 52 HIV-1-infected women and their infants in a prospective study on perinatal HIV transmission by the Bay Area Perinatal AIDS Center.

Results: The viral isolates from the transmitting mothers and their infants differed from the isolates from the nontransmitting mothers in their efficient replication in human PBMCs and in their ability to infect one or more human T-lymphocytic cell lines. All the HIV-1 isolates were able to infect human macrophages with only low-level replication and were unable to form syncytia in the MT-2-lymphocytic cells. No correlation between transmission and reactivity of maternal serum samples to the peptide corresponding to the principal neutralization domain of the third hypervariable region of the viral envelope was observed. However, the majority (9/12) of maternal isolates from the nontransmitters were neutralized by their autologous serum samples compared with only two among six in the transmitter group (P < .07). Moreover, five infant isolates were resistant to neutralization by their respective mother's serum samples, and one was sensitive to infection enhancement by the mother's serum. Another infant isolate was enhanced by his autologous serum.

Conclusions: Viral factors that appeared to correlate with mother-to-child transmission of HIV-1 observed in a small cohort included rapid or high-titered replication in human PBMCs, T-cell line tropism, and resistance to neutralization or a sensitivity to enhancement of infection by the maternal serum.