As a pharmacist my ears perked up at this topic and I listened with avid interest as medication safety in pregnancy is a question we are often asked about. One month ago the WHO issued a statement regarding a caution notification due to 4/426 babies with neural tube defects born to women in a study in Botswana who became pregnant whilst taking dolutegravir. This equated to 0.9% vs. 0.1% in the general population. The panel opened up this topic for discussion the implications of this data.
Dr Nicholas Paton from the National University of Singapore commented that our region has seen a massive uptake of dolutegravir, without, in his opinion, a lot of clinical data. Dr Paton advised given that “the train has left the station” i.e. dolutegravir is well and truly out there and in use in many countries globally, and given the recent outcomes from Botswana that we should “slow the train down”. Dr Paton highlighted the difficulty that if dolutegravir goes “full steam ahead” at this stage would cause significant standardization complexity in terms of 1st, 2nd and 3rd line treatments in regard to public health regimens and equity issues – i.e. different regimens / fixed dose combinations for men, women and pregnancy guidelines.
It was pointed out that conception is different to pregnancy, and WHO indicated dolutegravir can be started in the 3rd trimester. So where does this leave women already initiated on dolutegravir who have fallen pregnant or are wishing to become pregnant?
In terms of already being pregnant, the panel consensus appeared to be continue to take dolutegravir given that generally by the time you find out you are pregnant it is generally past the critical 28 days where neural tube development occurs. However, as a result of the data out of Botswana and the WHO statement, it is now recommended that women of child bearing age should have adequate contraception whilst taking dolutegravir.
This brought up a very relevant question from the audience regarding provision of adequate contraception being made available to countries and communities where access to preventative sexual health is limited. It was proposed that this needs to be part of the discussion and as health professionals we should advocate for contraceptive access for those women taking dolutegravir.
The question was raised as to whether this data was just a coincidence or a regional anomaly? The Botswana general population has a slightly higher neural tube defect rate and up to a .75% variation for neural tube defects opposed to some other countries like the USA. Were other factors at play such as folate deficiency? Clearly more intense data gathering is needed and at this time keep in mind that a “safety signal does not necessarily translate to causality” (Dr Kessler).
Watch this space – hopefully this time next year at the next APACC 4th annual conference more data will have emerged and may be able to provide more answers.
