Gene-nutrient interactions that impact magnesium homeostasis increase risk for neural tube defects in mice exposed to dolutegravir.

ABSTRACT: In 2018, data from a surveillance study in Botswana evaluating adverse birth outcomes raised concerns that women on antiretroviral therapy (ART) containing dolutegravir (DTG) may be at increased risk for neural tube defects (NTDs). The mechanism of action for DTG involves chelation of Mg²⁺ ions in the active site of the viral integrase. Plasma Mg²⁺ homeostasis is maintained primarily through dietary intake and reabsorption in the kidneys. Inadequate dietary Mg²⁺ intake over several months results in slow depletion of plasma Mg²⁺ and chronic latent hypomagnesemia, a condition prevalent in women of reproductive age worldwide. Mg²⁺ is critical for normal embryonic development and neural tube closure. We hypothesized that DTG therapy might

SUBMITTER: Gelineau-van Waes J 

PROVIDER: S-EPMC10292217 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature