BHIVA statement on Potential Safety Signal in Infants Born to Women Conceiving on Dolutegravir (on behalf of the BHIVA HIV in Pregnancy Guidelines Committee)

Tuesday 22nd May 2018

A preliminary unscheduled analysis of an ongoing birth surveillance study in Botswana has reported an increased risk of neural tube defects amongst infants of women who become pregnant whilst taking dolutegravir (DTG)-based regimens. The study reported 4 cases of neural tube defects out of 426 infants born to women who were on DTG-based regimens at the time of conception.

This rate of approx. 0.9% compares to a 0.1% of neural tube defects amongst infants born to women taking non DTG-based regimens at the time of conception.

We are awaiting prospective data on 600 women from Botswana and 400 in Brazil who were on DTG-based regimens at conception and have ongoing pregnancies.

Of note there have been no reported neural tube defects in infants born to a further 2000 women in the Botswana study who started DTG during pregnancy, including in first trimester.

In light of these preliminary findings the BHIVA HIV in Pregnancy Guidelines Writing group makes the following recommendations:

  • All women wishing to conceive should be started on folic acid 5mg OD regardless of their cART regimen

  • All women commencing DTG should have a negative pregnancy test prior to initiation and ongoing method of contraception documented

  • We advise a review of all patient records of women aged up to 50yo on DTG with regards to conception plans, documented method of contraception and current pregnancy status

  • We recommend that women at risk of pregnancy be contacted by their clinic to discuss the DTG safety report, which should be clearly documented, and the woman seen in person if pregnant

1. For a woman on DTG wishing to conceive

a. We advise switching to an alternative effective cART regimen

b. The best safety data for pregnancy is for efavirenz or atazanavir/r as per BHIVA HIV in Pregnancy Guidelines 2014

2. For a woman on DTG not planning children but of child bearing age

a. We advise a discussion on current method of contraception to be clearly documented

3. For a woman on DTG who becomes or is pregnant

a. We acknowledge the neural tube has closed within 4 weeks of conception but the EMA are recommending that women on DTG in the first trimester discontinue DTG. We therefore recommend that women in the first trimester on DTG switch to a regimen on which there is more safety data in pregnancy, such as efavirenz or atazanavir/r as per BHIVA HIV in Pregnancy Guidelines 2014

b. We do not recommend switching off DTG if in the second or third trimesters

c. If the physician/woman choose(s) to switch, use a regimen on which there is more safety data in pregnancy, such as efavirenz or atazanavir/r as per BHIVA HIV in Pregnancy Guidelines 2014

d. Detailed anomaly scans should be performed as per national pregnancy guidelines with no additional scans required

4. For a woman who is pregnant and not yet on cART

a. We advise using recommended cART such as efavirenz or atazanair/r as per BHIVA HIV in Pregnancy Guidelines 2014 (currently being updated and due for release this summer) available on www.bhiva.org/guidelines.aspx

Note that these findings are very preliminary and advice may change

For safety data on antiretrovirals please refer to the Antiviral Pregnancy Registry (www.apregistry.com) or seek advice from an expert colleague.

This report highlights the need to continue to prospectively report pregnancies to the National Study of HIV in Pregnancy and Childhood (www.ucl.ac.uk/nshpc) and the antiretroviral Pregnancy Registry (www.apregistry.com).

For further information:

European Medicines Agency (EMA)
http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2018/05/news_detail_002956.jsp&mid=WC0b01ac058004d5c1

WHO guidance
http://www.who.int/medicines/publications/drugalerts/Statement_on_DTG_18May_2018final.pdf?ua=1

FDA Statement
https://www.fda.gov/Drugs/DrugSafety/ucm608112.htm