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A highly effective HIV/AIDS drug often used by pregnant women may limit folate transport to the fetus, increasing the risk of birth defects. With new research funding, Reina Bendayan, a professor with the Leslie Dan Faculty of Pharmacy, will study whether dolutegravir and other antiretroviral drugs interfere with folate movement across the placenta to understand the effect of these drugs on neural tube defects.
Dolutegravir has been widely used to treat HIV/AIDS throughout much of the world, based on its high safety and effectiveness, as well as its reasonable cost. However, a recent study suggested that women in Botswana taking this drug at conception and throughout their pregnancy had babies with higher rates of neural tube defects, compared to women taking other antiretroviral drugs.
Based on this study, the World Health Organization stopped recommending this drug for women with HIV/AIDS of reproductive age, a major shift in its guidelines.
With her expertise in how drugs move across biological tissue barriers, Bendayan was immediately interested in this finding. “My team is well positioned to look at this question,” she says. “We have been working on HIV and antiretroviral drugs for years, and a few years ago we started a new line of research looking at folate transporters in the brain.” It was a natural fit to look at similar folate transporters in another tissue – the placenta.
With funding from the Ontario HIV Treatment Network, a non-profit supported by the Ontario Ministry of Health, her team will use human placenta cell lines and tissues to explore how dolutegravir and other antiretroviral drugs may interfere with the molecular mechanisms of that regulate folate movement across the placenta, potentially causing folate deficiency in the fetus.
They will also use models to study whether these drugs increase the risk of neural tube defects when the diet is either supplemented with or deficient in folate. This is a particularly important question, given that some populations with high rates of HIV also have poor access to folate-fortified diets and supplements, such as the women in the Botswana study.
“It is possible that countries with folate supplementation, such as Canada and the United States, may not have the same increase in neural tube defects due to these drugs as in developing countries,” says Bendayan. “But even here we have populations, such as Indigenous communities, that don’t have access to a folate-fortified diet or supplement.” For these at-risk populations, it may be particularly important to use HIV/AIDS drugs that do not affect folate transport, in order to reduce the risk of these defects.
“Our findings will inform on treatment guidelines in women of reproductive age who are living with HIV worldwide,” says Bendayan. “
