HIV-1 viruses transmitted at birth are resistant to antibodies in mother's blood

An infected mother can transmit HIV-1 to her child during pregnancy, while breastfeeding, or at the time of delivery. Antiretroviral drugs significantly reduce transmission risk, but these treatments are often not perfectly administered, particularly in resource-poor regions. Better understanding of how HIV-1 viruses are transmitted at delivery could inform new strategies to reduce infant HIV-1 infection.

Previous research has suggested that antibodies -- immune system proteins that can attack viruses -- in a mother might be less effective against certain genetic variants of HIV-1 in her body, thereby allowing for transmission of resistant viruses to her infant at delivery. However, this research has been inconclusive, so Kumar and colleagues designed a new study to address the question.

The research team analyzed HIV-1 viruses present in blood samples from 16 infants infected at delivery and their mothers; the samples had been collected in the early 1990s in the Women and Infants Transmission Study, before antiretroviral treatments were available. The researchers sequenced the HIV-1 variants, and for each mother-infant pair, they tested the sensitivity of both transmitted and non-transmitted viruses to antibodies concurrently present in the mother's blood.

The analysis revealed that most HIV-1 variants transmitted to the 16 infants at delivery were more resistant to the mothers' antibodies than were non-transmitted variants. However, the transmitted viruses were sensitive to a separate panel of broadly neutralizing HIV-1 antibodies, which can block infection of diverse HIV-1 strains. Genetic analysis uncovered particular sites in the membrane-proximal external region (MPER) and variable loop 3 (V3) of the HIV-1 envelope glycoprotein may be important in mediating maternal antibody resistance.

These findings could help guide development of a new vaccine for pregnant mothers with HIV-1. Such a vaccine would boost maternal antibody attack of HIV-1 variants circulating in the blood, so that transmission risk is reduced when an infant is exposed to maternal blood during delivery.