Metabolic implications and safety of dolutegravir use in pregnancy

Abstract

Dolutegravir is recommended for all people living with HIV because of its efficacy, high barrier to resistance, favourable safety and tolerability profile, and affordability. Dolutegravir has the highest rates of viral suppression in pregnancy, therefore preventing perinatal HIV transmission. In view of these benefits, particularly for pregnant women, an important question is if dolutegravir is safe in pregnancy. Dolutegravir has been associated with metabolic complications, including weight gain and rare events of hyperglycaemia, that could affect maternal, fetal, and postnatal health. We review the current clinically and experimentally based literature on the implications of dolutegravir use for pregnant women and for developing embryos and fetuses. Possible effects on folate status, energy metabolism, adipogenesis, and oxidative stress are considered. In many instances, insufficient data are available, pointing to the need for additional research in this important area of HIV treatment.

Figure 1.

Summary of the observed effects associated with DTG from animal and in vitro studies. DTG effects on folate metabolism^,–, cellular energy homeostasis^,, adipocyte function^,,,, and matrix metalloproteinases are shown (anticlockwise from top left). Dotted line indicates variable effects reported. Red arrows indicated increase/higher; blue arrows indicate decrease/lower, black arrow indicates unchanged. FRa, folate receptor 1; RFC, reduced folate carrier; PCFT; proton-coupled folate transporter; MMP, matrix metalloproteinases; PPARγ, peroxisome proliferator-activated receptor gamma; CEBPα, CCAAT/enhancer-binding protein alpha; UCP1, uncoupling protein 1; ROS, reactive oxygen species.