Coadministration of ARV (Atripla) and Topiramate disrupts quail cardiac neural crest cell migration

Congenital anomalies such as ventricular septal defects and truncus communis have been reported with the prenatal use of antiretroviral therapy. The mechanism of antiretroviral therapy teratogenicity is unclear and is therefore the focus of this study. Some human immunodeficiency virus patients on antiretrovirals are placed on antiepileptic drugs which are also teratogenic. The interactive effects arising from this therapeutic combination may affect their teratogenic propensity through their effects on neural crest cell migration.

Appropriately cultured neural crest cells from dissected neural tubes of 32-hr old quail embryos exposed to culture media containing peak plasma levels of Atripla, Topiramate and the combination of both were studied. Distance of migration of neural crest cells was measured using the migration assay and the cells were stained with rhodamine phalloidin to evaluate the cell actin. Also quail neural crest cells were brought into suspension and microinjected into chick hosts to determine the migration of the cells to the interventricular septum.

Migration of cultured neural crest cells was extensive in the control cultures, but inhibited in the treated groups. The experimental cultures showed a disarray of actin cytoskeleton contrary to normal distribution of actin filaments in controls. Significantly, few quail neural crest cells migrated to the interventricular septum of chick host embryos compared to the control cultures. The coadministration of topiramate with antiretroviral therapy does not seem to affect the activity of the antiretroviral drug.

These results indicate that Atripla and Topiramate cause ventricular septal defects by inhibiting the migration of cardiac neural crest cells.