(195) Exposure to Integrase-inhibitor Antiretroviral Drugs During Pregnancy and Congenital Abnormalities: A Case/Non-case Study from the International Pharmacovigilance Database Vigibase®

Friday, August 26, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 526

Presenting Author(s)

Anna-Belle Beau, PhD
– Post doctoral fellow, Department of Pharmacology, University Toulouse Hospital CERPOP, INSERM, Toulouse University, Toulouse, France

Co-Author(s)

Agnès Sommet
– Professor, CIC 1436, Team PEPSS « Pharmacologie En Population cohorteS et biobanqueS », Toulouse University Hospital, France, France
Laura Saint-Lary
– Unite Mixte de Recherche INSERM-Université 1027, Toulouse, France
Isabelle Lacroix
– CHU de Toulouse, Universit� de Toulouse, Inserm 1027, Toulouse, France
Valériane Leroy
– CERPOP, Inserm, Université de Toulouse, Université Paul Sabatier III, Toulouse, France, France

Background: More than 1.3 million pregnant women were living with HIV in 2018 and were eligible to receive an antiretroviral therapy, raising concerns about potential foetal effects. In 2018, the WHO reported an increased number of neural tube defects (NTD) after pre-conceptional exposure to dolutegravir, an integrase inhibitor (INI).

Objectives: We assessed the association between exposure to any and each individual INI and congenital abnormalities, compared to other antiretroviral drugs, using the international pharmacovigilance database VigiBase®.

Methods: We selected reports on any antiretroviral drugs registered in VigiBase® between 01/01/2007 and 30/03/2021 in children younger than two years exposed in utero or in pregnant women aged 12-50 years. A case/non-case study was conducted to evaluate the association between congenital anomalies and prenatal exposure to any and each INI, compared to other antiretroviral drugs, by estimating reporting odds ratio (ROR) and 95% confidence intervals. Cases were defined using the System Organ Classes "Congenital, familial and genetic disorders" and "Pregnancy, puerperium and perinatal conditions". RORs have been adjusted on reports location and date, and concomitant exposure to teratogenic drugs.

Results: We identified 2521 unique reports: 664 (26.3%) related to any INI; 1857 (73.7%) to other antiretroviral drugs. We identified 520 congenital abnormalities, cited in 327 unique reports, including 31.0% related to INI. We did not highlight a significant disproportionate reporting association between congenital anomalies and exposure to any INI during pregnancy, compared to other antiretroviral drugs (RORa 1.13 [0.85-1.51]). However, significant signals of disproportionate were reported for congenital anomalies of the urinary and digestive systems, and NTD.

Conclusions: Overall, we did not find significant disproportionate reporting association between all congenital anomalies and exposure to any INI during pregnancy. However, in subgroup analysis, we fouind specific signals, that needs to be further investigated in prospective studies.