PEPFAR Statement on Potential Safety Issue Affecting Women Living with HIV Using Dolutegravir at the Time of Conception

May 18, 2018

The U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) takes note of the May 18, 2018 statement by the World Health Organization (WHO) on “Potential safety issue affecting women living with HIV using dolutegravir at the time of conception.”

The investigator of an independent study funded by the U.S. National Institutes of Health has identified a potential safety issue with the HIV antiretroviral medicine dolutegravir (DTG), and reported it to the WHO and ViiV Healthcare. The potential safety issue is related to neural tube defects in infants born to women who were taking DTG at the time of conception; however, it is important to note that the data are very limited at this time.

The safety issue has been identified from a preliminary unscheduled analysis of an ongoing observational study in Africa, which has found four cases of neural tube defects out of 426 women who became pregnant while taking DTG. This rate of approximately 0.9 percent compares with a 0.1 percent risk of neural tube defects in infants born to women taking other antiretroviral medicines at the time of conception. More than 2,500 women who began taking DTG after the time of conception have not reported cases of neural tube defects.

The observational study in question is ongoing, and it is projected that there will be approximately 600 more births from pregnant women who were using DTG at time of conception. Their pregnancies will be monitored closely over the next nine months (May 2018 to February 2019), and the results from this group are expected to be known soon thereafter. These data will help provide more information about the safety of DTG for women living with HIV during conception.

The health and safety of patients PEPFAR supports remain its top priority. We look forward to the availability of further data from the ongoing observational study as well as that from additional studies of pregnant women. PEPFAR is working closely with the U.S. Centers for Disease Control and Prevention to understand the current limited data, and we will continue to coordinate closely with other relevant stakeholders and partners. We hope that future data will provide greater clarity about any potential safety issue with DTG for women during conception.

At this time, PEPFAR encourages countries to continue with their transition to DTG through the implementation of its 2018 Country Operational Plans. DTG offers many benefits, including that it is better tolerated by the patient, leads to improved outcomes such as faster viral suppression, and often costs less. DTG also has fewer side effects for most populations, which makes adherence to treatment easier. These factors are especially important for patients who are early in their progression of HIV disease and still feeling well.

Moving forward, PEPFAR will independently review all data and provide updates to its country programs. The transition times for tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) may be altered to allow for the use of efavirenz-based regimens for certain women. Until further data are available, under PEPFAR-supported programs, HIV-infected women who desire to become pregnant should take efavirenz-based regimens as a safe and effective first-line regimen. Given the lack of signals of potential safety issues with the use of DTG for all other populations, DTG should be used as their first-line regimen in all PEPFAR-supported programs.