US, EU Warn About Birth Defect Risk From Dolutegravir

Troy Brown, RN

May 18, 2018

The US Food and Drug Administration (FDA) and the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) have warned that women with HIV who take dolutegravir (Tivicay, GlaxoSmithKline) at the time of conception or during the first trimester of pregnancy appear to be at higher risk of giving birth to infants with neural tube defects, including spina bifida.

The FDA advises healthcare providers to explain the risks and benefits of dolutegravir to women of childbearing age and consider other non–dolutegravir-containing antiretroviral medications because neural tube defects can develop before women are aware they are pregnant. Women of childbearing age should undergo pregnancy testing before initiating the medication and consistently use effective contraception while taking dolutegravir.

Women who are already taking dolutegravir should not stop the medication before talking with their healthcare provider because doing so can worsen the infection.

Dolutegravir is an integrase inhibitor that prevents the virus from multiplying. It is not a cure for HIV or AIDS but may slow immune system damage and the development of infections and AIDS-associated diseases.

The FDA approved dolutegravir in 2013. It is also available in a fixed-dose combination with lamivudine and abacavir (Triumeq, ViiV Healthcare) and with rilpivirine (Juluca, ViiV Healthcare).

The warnings follow consideration of preliminary data from a study conducted in Botswana that included 11,558 HIV-infected women in which infants born to mothers taking the medication appeared to have an increased risk for neural tube defects.

Of 426 women who became pregnant while taking the medication, 4 (0.9%) infants were born with neural tube defects, such as spina bifida, compared with 14 (0.1%) of 11,173 mothers who took other HIV medications. Final study results will be available in approximately 1 year.

The risk appears to be higher among women who received dolutegravir at the time of conception or early in the first trimester, when the spinal cord, brain, and related structures are forming. No neural tube defects were reported among women who began the drug later in pregnancy.

EMA Also Issues Warning

The EMA issued similar warnings, according to an EMA news release.  

Women who are taking dolutegravir and have a confirmed pregnancy during the first trimester should change to an alternative HIV treatment unless none are available. The EMA also advises that the medication should not be prescribed for women of child-bearing potential who are trying to become pregnant and that women of child-bearing potential who are using the drug to use contraception throughout treatment.

While the EMA awaits final study results, it also advises women against stopping the medication without consulting their physician. The EMA will update its recommendations as needed after it completes its assessment.

Reproductive toxicology studies, data from the Antiretroviral Pregnancy Registry, clinical trials, and postmarketing use have shown no increased risk for neural tube defects.

These recommendations will be sent by letter to healthcare professionals in the European Union.

Dolutegravir was authorized in the European Union in 2014 and is also authorized in combination with lamivudine and abacavir (Triumeq). The EMA's Committee for Medicinal Products for Human Use gave a positive opinion for the combination of dolutegravir and rilpivirine (Juluca) in March 2018 and is waiting for a decision from the European Commission.

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