Transmission of HIV-1 in the Face of Neutralizing Antibodies

Abstract

In most cases of HIV-1 transmission, only a subset of variants is transmitted from the index case to the newly infected individual. Understanding the characteristics of these transmitted variants may aid in developing new methods to halt the spread of HIV-1. Studies evaluating the genotypic and antigenic properties of transmitted variants have provided insights into how the selective pressures applied during different modes of transmission uniquely imprint the infecting viruses. In the setting of sexual transmission, variants with increased neutralization sensitivity appeared to be selected during transmission in discordant subtype C-infected couples, although transmitted variants from different risk groups and HIV-1 subtypes did not demonstrate increased neutralization sensitivity, suggesting this may not be a consistent feature of transmitted variants. Studies of both mother to child transmission (MTCT) and superinfection, where preexisting NAbs are present at the time of exposure, provide opportunities to analyze whether the breadth and potency of the NAb response influence the incidence of new infections. MTCT resulted in selection for variants that were resistant to maternal antibodies, suggesting that maternal antibodies can protect the baby from those variants that are susceptible to the antibodies present. There are some data to suggest that poor neutralizing antibody (NAb) responses are present in cases of superinfection, although these data are preliminary. Defining the characteristics of the viruses transmitted in the presence and absence of NAbs as well as defining the NAb responses that fail to protect from infection during MTCT and superinfection may provide critical insights into the antibody responses that are needed for effective vaccines and other prophylactic therapeutics.