HIV treatment guidelines were updated in 2019 by the World Health Organization (WHO) as dolutegravir, an inhibitor of the integrase enzyme becomes the preferred first-line and second-line treatment regimen in the highly active antiretroviral therapy (HAART).
The government of Uganda in support of its partners set out to roll out the countrywide switching of eligible patients living with HIV to a dolutegravir-based regimen. However, for women of childbearing age, the clinical team required written consent to prescribe the drug. The patient also assured the clinical team that she would use contraception for as long as she was taking dolutegravir or else they could not switch for fears that dolutegravir increased the risks of neural tube defects.
These fears were, however, alleviated by WHO following the 10th IAS Conference on HIV Science in Mexico City, Mexico, when data, particularly from the ADVANCE trial showed no relationship between dolutegravir and the development of neural tube defects whatsoever. The benefits outweighed the risks- if any.
We expound on these findings in this article to enable health care providers to attend to people living with HIV when they are on dolutegravir. To provide adequate information to them and help them make an informed decision in addition to alleviating any fears that may have arisen.
To not be misquoted on this matter, there are no ‘safe’ drugs in pregnancy. We instead have those that are generally acceptable to use in pregnancy. Let’s get this started.
WHO recommended dolutegravir as the preferred first-line and second-line HIV treatment for all populations, pregnant women and those of childbearing capability inclusive. There was an alarm about the safety concerns of dolutegravir in Botswana when 4 of the newborns developed neural tube defects in 426 women who had conceived whilst taking dolutegravir.
However, the following two large clinical trials conducted in Africa that compared the efficacy and safety of dolutegravir and efavirenz showed that the risk of delivering a baby with a neural tube defect by women taking dolutegravir was lower than initially stated.
The ADVANCE trial results were presented at the 10th IAS Conference on HIV Science in July 2019 and reaffirm the results from the studies from Africa. To summarize the ADVANCE trial, 65 pregnancies occurred, with 43 of these happened to women while taking dolutegravir. 43.1% live births occurred, 12.3% miscarriages occurred, 24.6% were elective abortions. There were one stillbirth and one neonatal death. The babies’ median birth weights were similar across all the groups throughout the trial but, 7.1% of the births were premature, and 17.2% were small for gestational age. Two infants had minor congenital anomalies. Of importance, there was no vertical transmission of HIV that occurred.
Another study conducted in Brazil with results presented at the same conference, researchers investigated the relationship between dolutegravir and neural tube defects. They enrolled 1468 women, with 382 receiving dolutegravir and 1086 receiving either efavirenz and raltegravir or raltegravir only. There were 6.5% stillbirths or abortions in the dolutegravir group: 4.5% in the efavirenz or raltegravir groups.
The primary outcome was that no neural tube defects occurred. It was, however, noted that in Botswana, there’s no fortification of food so, there’s a possibility that the four neural tube defects seen in that initial study could be related to lack of enough folic acid among the affected women.
Related article: COVID-19 in Pregnancy: Is there a need to worry?
Dolutegravir easily crosses the placenta. It is superior to the drug alternatives that the clinicians were using to combat the HIV pandemic. It is because it is more effective, friendly to take and has fewer side effects. Important to note, though, that the clinical committee rolled the drug following the survey pioneered by WHO among 18 countries, 12 of which had pretreatment drug resistance levels exceeding the recommended 10%.
Do not swallow dolutegravir within 2 hours of ingesting any preparation containing iron, calcium or prenatal vitamins. It is worth noting.
In a nutshell, there’s a need to increase community awareness, as well as, health care providers’ knowledge base about the HIV guidelines, especially when it comes to what information to disseminate among patients that can enable them to make informed choices. Together we can fight HIV.
Thanks for reading.