No developmental toxicity observed with dolutegravir in rat whole embryo culture.

Background: An in vitro rat whole embryo culture study investigated whether direct exposure to dolutegravir (Tivicay ) during the critical period for neural tube development would result in abnormal development.

Methods: Dolutegravir (DTG), and HIV integrase inhibitor, was administered at 0 (vehicle), 5.3 μg/mL and 9.

Absence of developmental and reproductive toxicity in animals exposed to dolutegravir.

The success of new antiretroviral medicines for HIV resulted in a change to guidelines of standard therapy where continuation of antiretroviral therapy is recommended to maintain the low viral load during pregnancy, thereby preventing transmission of the virus to the fetus. As a result, pregnancy related exposure to HIV medicines has increased. Understanding the safety of these medicines during pregnancy is of paramount importance to ensure health of mothers and their offspring; well-designed animal studies that evaluate the reproductive life cycle play a key role in this effort.

Clinical Extrapolation of the Effects of Dolutegravir and Other HIV Integrase Inhibitors on Folate Transport Pathways.

Preliminary analysis of ongoing birth surveillance study identified evidence of potential increased risk for neural tube defects (NTDs) in newborns associated with exposure to dolutegravir at the time of conception. Folate deficiency is a common cause of NTDs. Dolutegravir and other HIV integrase inhibitor drugs were evaluated in vitro for inhibition of folate transport pathways: proton-coupled folate transporter (PCFT), reduced folate carrier (RFC), and folate receptor (FR)-mediated endocytosis.