Efficacy and safety of dolutegravir containing ART regimens in HIV-1-infected pregnant women and their infants

Due to actual reasons, the press release of this week summarizes the latest news of the IMPACT 2010 study, investigating the efficacy and safety of dolutegravir containing antiretroviral therapy in pregnant women. So far, productive toxicology studies and other data on the use of dolutegravir in pregnancy, including data from the Antiretroviral Pregnancy Registry (APR), clinical trials and post-marketing use did not indicate a risk of neural tube defects.

The IMPACT 2010 study was launched by the National Institute of Healthy, is a phase 3 study, and aimed to enroll 639 women who are 14 to 18 weeks pregnant, are living with HIV, and are not currently taking antiretroviral treatment. The women were randomly assigned to be administered efavirenz/emtricitabine/tenofovir fumarate disoproxil (EFV/FTC/TDF), dolutegravir/FTC/tenofovir alafenamid fumarate (DTG/FTC/TAF), or DTG/FTC/TDF. Their infants were also enrolled in the study and received local standard-of-care interventions for HIV prophylaxis following birth. Both the women and their infants were followed for 50 weeks after delivery. Participating clinical trial sites included the United States, Zimbabwe, Botswana, Brazil, Haiti, India, Malawi, South Africa, Tanzania, Thailand, and Uganda. The final results of the study are expected in about a year.

So far, the study looked at babies born to 11’558 HIV-infected women in Botswana and showed that 0.9% of babies (4 of 426) whose mothers became pregnant while taking dolutegravir had a neural tube defect, compared with 0.1% of babies (14 of 11’173) whose mothers took other HIV medicines. No cases were reported in infants born to women who started dolutegravir later during pregnancy.

In conclusion, this preliminary data suggest that the potential safety issue arises from a woman’s exposure to dolutegravir at the time of conception, rather than during pregnancy. Currently, there is no evidence of any infant born with a neural tube defect to a woman who started dolutegravir during her pregnancy. As a precaution, healthcare are advised of the following:

• Do not prescribe dolutegravir for women of childbearing potential who are trying to become pregnant.
• Exclude pregnancy in women of childbearing potential before starting dolutegravir.
• Advise women of childbearing potential who are taking dolutegravir to use effective contraception throughout treatment
• If pregnancy is confirmed in the first trimester while a woman is taking dolutegravir, switch to an alternative treatment unless there is no suitable alternative

Comment Dr. Dominique Braun and Prof. Huldrych Günthard, SHCS
As a direct consequence from this preliminary results, HIV post-exposure prophylaxis (PEP) with dolutegravir should not be prescribed to women of childbearing potential unless a pregnancy has been ruled out before starting PEP. With regard to the consequences for the Simpl’HIV study, the sponsor team in Geneva is currently preparing an information letter that will distributed soon.