Use of HIV medication during pregnancy in Germany

Background: In women with HIV, antiretroviral therapy (ART) is recommended during pregnancy to avoid progression and vertical transmission. In 2018, an increased risk of neural tube defects was observed for dolutegravir (DTG) and an increased risk of therapy failure during pregnancy was seen for combinations of elvitegravir (EVG) and darunavir (DRV) with cobicistat (COB).

Objectives: To describe ART use before and during pregnancy with focus on DTG and EVG/DRV+COB and changes since 2018.

Methods: Using data from the German Pharmacoepidemiological Research Database (GePaRD), we identified all pregnancies between 2005–2020 in a cohort of female ART users aged 13-49 years and assessed all ART dispensings before and during pregnancy. To examine changes since 2018, we compared proportions of ART use in the time windows ‘from start of availability of respective substance/combination to 2017’ and ‘2018-2020’. The study was financed by the German Federal Institute for Drugs and Medical Devices (BfArM).

Results: In a cohort of 5,347 female ART users, we identified 1,754 pregnancies. 965 (55%) pregnancies were exposed at pregnancy onset, 458 (26%) started ART during pregnancy and in 331 (19%) ART was stopped before onset. The recommended ART classes nucleoside reverse transcriptase inhibitors, protease inhibitors and integrase inhibitors were used in 98%, 31%, and 13% of pregnancies.
At pregnancy onset, 7% of pregnancies were exposed to DTG, both 2014-2017 and 2018-2020. DTG was discontinued in 30% of exposed pregnancies in 2014-2017 and in 57% of exposed pregnancies in 2018-2020. Discontinuation occurred in median 7.4 weeks after pregnancy onset. EVG+COB was discontinued during pregnancy in 38% of exposed pregnancies (n=45) in both time windows. DRV+COB was stopped in all exposed pregnancies (n=9) in both time windows. Combinations were stopped in median 8.1 and 7.1 weeks after pregnancy onset. ART was started in 8 pregnancies with DTG (4 in each time window), in 3 pregnancies with EVG+COB (all 2014-2017) and in 1 pregnancy with DRV+COB (2018-2020). DTG was discontinued in 17 (3%) of the pregnancies that were exposed to ART but not to DTG at pregnancy onset, in median 6 months before onset.

Conclusions: Predominantly, recommended ART classes during pregnancy were used. Exposure to DTG and EVG/DRV+COB during pregnancy was already low and decreased further after 2018.