Statement on Potential Safety Signal in Infants Born to Women Taking Dolutegravir from the HHS Antiretroviral Guideline Panels

The HHS Antiretroviral Guidelines Panels¹ are issuing this statement in response to a potential safety signal in infants born to women who were taking dolutegravir (DTG)-based antiretroviral (ARV) drug regimens at the time of conception in accordance with guidance from another federal agency.²

The concern stems from a preliminary unscheduled analysis of an ongoing NIH-funded birth surveillance study in Botswana, which has reported an increased risk of neural tube defects among infants of women who became pregnant while taking DTG-based regimens. The study reported 4 cases of neural tube defects out of 426 infants born to women who became pregnant while taking DTG-based regimens. This rate of approximately 0.9% compares to a 0.1% risk of neural tube defects among infants born to women taking non-DTG-based regimens at the time of conception.³

The same study has yielded no evidence of neural tube defects among infants born to women who initiated DTG-based regimens during pregnancy.

The study in Botswana is ongoing, and results from additional pregnant women who were using DTG-based regimens at the time of conception are expected over the next 9 to 12 months.

Until more information is available, the Panels’ INTERIM recommendations are:

• Health care providers are encouraged to counsel women of childbearing age with HIV currently receiving DTG about this newly identified potential risk.
• Pregnant women with HIV who are currently taking DTG should not stop their ARV therapy and should speak with their health care provider for additional guidance.
• Women of childbearing age with HIV who desire to become pregnant should discuss alternative ARV regimen options with their health care provider.
• Women of childbearing age with HIV who are not planning to become pregnant may be on DTG-based regimens provided their pregnancy test before initiation of therapy is negative, and they consistently use a reliable contraceptive method.
• Health care providers are encouraged to report all pregnancy data to the Antiretroviral Pregnancy Registry (1-800-258-4263; http://www.apregistry.com).

The Office of AIDS Research Advisory Council will review the proposed changes to the guidelines at the earliest opportunity.

1. The Panel on Antiretroviral Guidelines for Adults and Adolescents, the Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV, and the Panel on Treatment of Pregnant Women Living with HIV and Prevention of Perinatal Transmission
2. https://www.fda.gov/Drugs/DrugSafety/ucm608112.htm
3. http://www.who.int/medicines/publications/drugalerts/Statement_on_DTG_18May_2018final.pdf?ua=1