Insufficient data on risk of neural tube defects with exposure to elvitegravir or bictegravir exposure during preconception or first trimester
Polly Clayden, HIV i-Base
A review of the Gilead global safety database, found no evidence of increased risk of neural tube defects (NTDs) with elvitegravir (EVG)- and bictegravir (BIC)-exposed pregnancies.
But this conclusion was based on limited (and extremely limited) numbers with all the usual caveats when many cases originate from retrospective reports drawn from a population in which the denominator is unknown.
Findings from this review, conducted by the company, were presented at Glasgow HIV 2018. All pregnancies reported for women exposed to EVG- and BIC-containing products from the beginning of clinical development to 31 May 2018 were retrieved from the database. These cases were from clinical trials, Antiretroviral Pregnancy Registry (APR), spontaneous post marketing reports and literature review.
There were 630 EVG-exposed pregnancies of which 155 were prospectively reported and included preconception or first trimester exposure. There were no prospectively reported NTD cases.
One retrospective NTD was reported: a 34-year-old woman in the US who received EVG/cobicistat (COBI)/emtricitabine (FTC)/tenofovir alafenamide (TAF) before conception and then switched to raltegravir (RAL) + FTC/tenofovir disoproxil fumarate (TDF) 48 days after her last menstrual period. Medications started before conception were folate and metronidazole. An ultrasound 19 weeks after her last period showed anencephaly. She had a medical abortion at 19 weeks.
On 10 October 2018 (after the data lock for this review), another retrospective NTD case from 2014 was reported: a French woman of unknown age started EVG/COBI/FTC/TDF two weeks after her last menstrual period. Myelomeningocele was reported at 14 weeks gestational age and she had a medical abortion two weeks later.
For BIC-containing products, 25 pregnancy cases were identified, of which 18 were prospectively reported and included preconception or first trimester exposure. There were no cases of NTD found with review of the limited data from BIC.
The study investigators concluded: “Viewed in the context of more than 600 EVG-exposed pregnancies these two cases cannot be distinguished from the background rate in the general population”.
Yet they also wrote: “A prevalence rate could not be derived from these data, as many cases originated from retrospective reports, drawn from a population in which the number of exposed pregnancies is unknown”.
And finally: “Currently, there is no evidence of an increased risk of EVG- or BIC-containing products during pregnancy”.
It is always encouraging to see originator companies present safety reviews of their products publicly (and not only for birth outcomes). But as the 600 EVG-exposed pregnancies had a lot of missing data, including timing of exposure, and there were only 25 BIC-exposed ones, a better conclusion might be that there is insufficient evidence to dismiss or confirm a potential risk of NTDs with EVG or BIC.
Farrow T et al. Cumulative safety review of elvitegravir and bictegravir use during pregnancy and risk of neural tube defects.HIV Glasgow.
28–31 October 2018. Glasgow, UK. Poster abstract P030.