Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Revista
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
AIDS ; 38(4): 439-446, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37382903

RESUMO

OBJECTIVES: In 2018, the Botswana Tsepamo Study reported a nine-fold increased risk of neural tube defects in infants whose mothers were treated with dolutegravir (DTG) from the time of conception. As maternal folate supplementation and status is a well known modifier of neural tube defect (NTD) risk, we sought to evaluate birth outcomes in mice fed normal and low folic acid diets treated with DTG during pregnancy. DESIGN: DTG was evaluated for developmental toxicity using pregnant mice fed normal or low folic acid diet. METHODS: CD-1 mice were provided diet with normal (3 mg/kg) or low (0.3 mg/kg) folic acid. They were treated with water, a human therapeutic-equivalent dose, or supratherapeutic dose of DTG from mouse embryonic day E6.5 to E12.5. Pregnant dams were sacrificed at term (E18.5) and fetuses were inspected for gross, internal, and skeletal defects. RESULTS: Fetuses with exencephaly, an NTD, were present in both therapeutic human equivalent and supratherapeutic exposures in dams fed low folic acid diet. Cleft palates were also found under both folate conditions. CONCLUSIONS: Recommended dietary folic acid levels during mouse pregnancy ameliorate developmental defects that arise from DTG exposure. Since low folate status in mice exposed to DTG increases the risk for NTDs, it is possible that DTG exposures in people living with HIV with low folate status during pregnancy may explain, at least in part, the elevated NTD risk signal observed in Botswana. Based on these results, future studies should consider folate status as a modifier for DTG-associated NTD risk.


Assuntos
Infecções por HIV , Defeitos do Tubo Neural , Oxazinas , Piperazinas , Piridonas , Humanos , Gravidez , Feminino , Animais , Camundongos , Ácido Fólico/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA