In 2018, the Tsepamo study released an early warning of an association between Dolutegravir exposure and neural tube defects. Today, the long awaited follow up data was presented. The initial warning, in 2018, followed the discovery of four cases of neural tube defects in 426 women who were taking dolutegravir during conception. Resulting in a NTD rate of 0.94%, significantly higher than the background risk in Botswana of 0.09%.
To address and further study these concerning results, many more clinics were opened in Botswana to gather further data on neural tube defects. Results released today show that a total of 1683 women were exposed to dolutegravir during conception which resulted in a total of 5 births with neural tube defects. The overall prevalence then fell to 0.3%. Fortunately this is a lot lower figure than the original 0.94%, however it remains a statistically significant increase.
Notably, Botswana does not have folate fortified foods, leading to a background prevalence of 0.09% of neural tube defects. This can be compared with a prevalence of around 0.06% in countries which do have folate fortified foods.
A study from Brazil, which does have folate fortified foods, showed no neural tube defects in women taking dolutegraivr at conception. (No Occurrences of neural tube defects among 382 women on dolutegravir at pregnancy conception in Brazil. Speaker: Fernanda Fernandes Fonseca) Unfortunately, this study from Brazil, lacks power, given there were only 382 women included in the study.
The Tsepamo study raises several questions. Firstly, does the lack of folate supplementation in women in Botswana, in combination with dolutegravir, cause the raised rates of NTD? Would folate supplementation while using dolutegravir reduce the risk of NTD to the background rates? We know that women taking other medications (i.e. anti epileptics) are recommended to take higher levels of folate supplementation during the preconception and early pregnancy period. This hasn´t led to a blanket ban of those medications in all women.
Secondly, how does this small, yet increased risk of NTD affect our practice in Australia? Should dolutegravir only be recommended to women in combination with contraception? Or should this medication be offered to any woman with appropriate discussion of the risks/benefits? The WHO guidelines have recommended that dolutegravir be offered to all women as first line treatment for HIV infection. This is a result of modelling suggesting that the overall benefits of dolutegravir outweigh the risks when compared with efavirenz in these communities. However, women in Australia have access to alternate options and resistance profiling which is likely to reduce the benefits of dolutegravier as perceieved by the modelling. There is a lack of good data available in Australian settings to be able to give a clear answer. Clinicians will need to take a patient centred approach and discuss the risks and benefits of the various treatment options.
Dr Lucy Donovan has worked as a General Practitioner at Prahran Market Clinic (a high case load GP clinic in Victoria) since 2018. She is currently completing Sexual Health Physician Training through RACP. Prior to this she completed a Master of Public Health and Tropical Medicine through James Cook University.