The Therapeutic Goods Administration (TGA) has issued a safety advisory regarding the use of dolutegravir during pregnancy. Dolutegravir is an integrase inhibitor indicated for the treatment of HIV infection in combination with other antiretroviral agents. It can be found in Tivicay® and the fixed-dose combination product Triumeq®.
Preliminary results from the Botswanan Tsepamo Study identify a potential increased risk of neural tube defects in babies born to women taking dolutegravir at the time of conception. This study followed the babies of 11,558 HIV-positive women. Of the babies whose mothers took dolutegravir at conception, 0.94% (4/426) had a neural tube defect compared to 0.13% (14/11,173) of babies whose mothers took other antiretroviral medications. No cases of neural tube defects were reported in the more than 2,500 infants born to mothers who began treatment with dolutegravir later in their pregnancy.
Previous studies have not shown an increased risk of foetal abnormalities when dolutegravir is initiated during pregnancy. However, more data is required regarding the effects of dolutegravir when taken during the crucial development period following conception. Final results of the Tsepamo Study are expected to be delivered within 12 months. In the interim, the TGA makes the following recommendations:
- Do not prescribe dolutegravir to women who are trying to become pregnant;
- Exclude pregnancy before initiating dolutegravir in women of child-bearing potential;
- Advise women of child-bearing potential to use effective contraception during treatment with dolutegravir; and
- Switch to an alternative agent (if appropriate) if pregnancy is confirmed in the first trimester in a woman taking dolutegravir.
- Department of Health. Dolutegravir: safety advisory – new study suggests possible risk of birth defects. Woden: Therapeutic Goods Administration; 2018.
- Mofenson LM. In-utero ART exposure and the need for pharmacovigilance. Lancet Glob Health. 2018; pii: S2214-109X(18): 30272-9.