FDA and EMA warns about birth defects from HIV drug dolutegravir

The infants born to women taking human immunodeficiency virus (HIV) drug dolutegravir (Tivicay) at the time of conception or during the first trimester of pregnancy, may develop neural tube defects, including spina bifida. The warning was issued by both US Food and Drug Administration (FDA) and the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA).

According to FDA, preliminary results from an ongoing observational study in Botswana found that women who received dolutegravir at the time of becoming pregnant or early in the first trimester appear to be at higher risk for these defects.

Neural tube defects are birth defects that can occur early in pregnancy due to malformation of the spinal cord, brain, and related structures.

Dolutegravir is an antiretroviral medicine which is used for the treatment of HIV in combination with other antiretroviral medicines. It was approved by FDA in 2013. It works by blocking integrase, an HIV enzyme, to prevent the multiplication of virus and reduce the amount of HIV in the body.

FDA recommendations for healthcare professionals:

• Weigh the benefits and the risks of dolutegravir when prescribing antiretroviral medicines to women of childbearing age. Alternative antiretroviral medicines should be considered. Discuss the relative risks and benefits of appropriate alternative antiretroviral therapies.


• If the decision is made to use dolutegravir in women of childbearing age, healthcare professionals should reinforce the consistent use of effective birth control.


• Perform pregnancy testing before initiating a dolutegravir-containing regimen in women of childbearing age to exclude pregnancy.


• Inform women of childbearing age about the potential risk of neural tube defects when a dolutegravir-containing regimen is used at the time of conception and early in pregnancy.

FDA recommendations for HIV patients:

• If you are already pregnant, stopping your dolutegravir-containing regimen without switching to alternative HIV medicines could cause the amount of virus to increase and spread HIV to your baby.


• Do not stop taking dolutegravir without first talking to your healthcare professional because stopping your medicine can cause the HIV infection to worsen.


• You should tell your healthcare professional if you are pregnant or are planning to become pregnant before you start a dolutegravir-containing regimen. Your health care professional may discuss other treatment options with you.


• Women of childbearing age who decide to take a dolutegravir-containing regimen should consistently use effective birth control (contraception) while on HIV treatment. Women should talk to their healthcare professionals about an effective birth control method to use while taking a dolutegravir-containing regimen.


• Before you start a dolutegravir-containing regimen you will need a pregnancy test to determine if you are already pregnant.


• Women of childbearing age should talk to their healthcare professional about other non-dolutegravir-containing antiretroviral medicines.

According to the observational study, whose final results are yet to published:

• 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.


• 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.

"To date, in this observational study there are no reported cases of babies born with neural tube defects to women starting dolutegravir later in pregnancy," the FDA added. "We are investigating this new safety issue and will update the public when we have more information."