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Metabolic implications and safety of dolutegravir use in pregnancy
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The global HIV pandemic presents a severe health-care burden, which can be successfully managed by ART. Dolutegravir-based ART is a preferred treatment option in both resource-rich and resource-limited settings because of its efficacy, high barrier to resistance, favourable safety and tolerance profile, and affordability.
Dolutegravir-associated changes to maternal physiology, such as weight change, hyperglycaemia, and folate metabolism, along with changes to adipose tissue, oxidative stress, and potential interference with metal-binding enzymes, might affect fetal development and influence metabolic health in the child. However, the degree to which the reported cellular changes affect physiology remains unclear, and whether targeting these pathways in treatment would improve the dolutegravir-specific side-effects observed clinically is unknown. Furthermore, despite increasing evidence of dolutegravir-associated metabolic changes in non-pregnant adults, there have not been similar reports in pregnancy, and their connection to fetal development has not yet been studied. Studies investigating maternal metabolic health, such as weight and adipose change, plasma lipid profile, adipokine concentrations, glucose homoeostasis correlating to pregnancy outcomes, and long-term fetal health, are warranted.
Specifically, addressing the following questions would provide great insight. Does dolutegravir affect maternal metabolic health? Do changes in maternal metabolic health resulting from dolutegravir treatment affect pregnancy outcomes and fetal metabolic health? How does maternal nutritional status interact with dolutegravir to influence birth outcomes? In clinical practice, increasing the focus on monitoring of maternal health and metabolic alterations occurring because of dolutegravir treatment is pertinent. Further, given the scale at which ART is being used in pregnancy, it is important that systematic monitoring of adverse events and pregnancy and birth outcomes is implemented because even small changes in risk have the potential to translate into many pregnancies and babies affected. In the absence of a mechanistic understanding, adequate nutrition and folic acid supplementation should be encouraged.
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