In the pre-
highly active antiretroviral therapy (
HAART) era, prenatal "vertical" mother-to-child transmission (MTCT) of HIV was about 25% and exposure of pregnant mothers to drugs of abuse (
illicit drugs and tobacco smoking) was a significant contributory factor of MTCT. However, with the introduction of
HAART, the rate of MTCT of HIV has decreased to less that 2%. But, it is estimated that currently about 5.1% of pregnant women use
illicit drugs and 16.4%
smoke tobacco. The residual prevalence of MTCT is of concern and may be related to this continued prevalence of
substance use among pregnant mothers. In this report, we review and present evidence that supports the hypothesis that drugs of abuse do have the potential to increase MTCT of HIV in the presence of
HAART. Exposure to drugs of abuse during pregnancy may increase MTCT of HIV through a variety of mechanisms that are addressed in detail including possible damage to the placenta, induction of
preterm birth, and increasing maternal plasma viral load though a variety of putative mechanisms such as: (a) promoting HIV replication in monocyte/macrophages; (b) increasing the expression of
CCR5 receptors; (c) decreasing the expression of
CCR5 receptor ligands; (d) increasing the expression of
CXCR4 receptors; (e) increasing the expression of
DC-SIGN; (f) impairing the efficacy of
HAART through
drug-drug interaction; and (g) promoting HIV mutation and replication through non-adherence to
HAART.