Biological mechanisms of vertical human immunodeficiency virus (HIV-1) transmission

Abstract

In the absence of interventions, 30-45% of exposed infants acquire human immunodeficiency virus type 1 (HIV-1) through mother-to-child transmission. It remains unclear why some infants become infected while others do not, despite significant exposure to HIV-1 in utero, during delivery and while breastfeeding. Here we discuss the correlates of vertical transmission with an emphasis on factors that increase maternal HIV-1 levels, either systemically or locally in genital secretions and breast milk. Immune responses may influence maternal viral load, and data suggest that maternal neutralising antibodies reduce infection rates. In addition, infants may be capable of mounting HIV-specific cellular immune responses. We propose that both humoral and cellular responses are necessary to reduce infection because cell-free as well as cell-associated virus appears to play a role in vertical transmission. These distinct forms of the virus may be targeted most effectively by different components of the immune system. We also discuss the use of antiretrovirals to reduce transmission, focusing on the mechanisms of action of regimens currently used in developing country settings. We conclude that prevention relies not only on reducing maternal HIV-1 levels within blood, genital tract and breast milk, but also on pre- and/or post-exposure prophylaxis to the infant. However, HIV-1 has the capacity to mutate under drug pressure and rapidly acquires mutations conferring antiretroviral resistance. This review concludes with data on persistence of low-level resistance after delivery as well as recent guidelines for maternal and infant regimens designed to limit resistance.