Introduction:
Antiretroviral therapy (ART) is recommended worldwide for all persons with Human Immunodeficiency Virus (HIV), including pregnant women. The use of this technology has resulted in a decreased risk of perinatal transmission to < 1 % in Denmark and other high-income countries. No single ART regimen has however consistently been considered first-line for pregnant women and exposure to HIV and/or different ART drugs during pregnancy may be associated with an increased risk of adverse birth outcomes. The objective of this nationwide study is to describe ART regimens during pregnancy among women living with HIV (WWH) in Denmark, including regimen changes during pregnancy, and to examine the association between ART use in pregnancy and other risk factors, and different adverse birth outcomes. This to evaluate the possible side effects of the technology and to have the results implemented in the midwifery education and practice.

Material and Methods:
A Danish population-based cohort study including all pregnancies among WWH in Denmark between 2000 and 2019. Data was collected through national registries. Temporal trends of ART use in pregnancy were evaluated. Logistic regression models were used to examine the association between ART use in pregnancy (regimen, PI-use, and time of ART initiation in pregnancy) and other risk factors with different adverse birth outcomes (preterm birth, small for gestational age, intrauterine growth restriction, and low birth weight).

Results:
In total, 589 pregnancies were included. The mean age at delivery was 33 years (95% CI 32.2-33.1). Most women were born abroad, with more than half of the women originating from an African country (58%), and most were diagnosed with HIV prior to conception (81%) and were well-treated with an HIV RNA <50 copies/mL at delivery (86%). In total, 65% (n=385) of the WWH were on ART at conception, which increased over time from 54% in the early study period to 75% in the late study period. Combination treatment with a Nucleoside Reverse Transcriptase Inhibitor (NRTI) and a Protease Inhibitor (PI) was the most common regimen (96%). NNRTIs were the least commonly used drug class (26%) together with InSTIs. The proportion of women receiving InSTIs after 2008, when raltegravir was licensed, was 9% (33/370). An increase in InSTI-based regimens in pregnancy, especially dolutegravir (DTG) use, is seen in recent years. In total, 118 (20%) women changed their ART regimen during pregnancy. Change was more common in women, who were diagnosed with HIV prior to conception (n=102 (86%)) than among women diagnosed with HIV in pregnancy (n=16 (14%)). ART regimen, PI use in pregnancy and timing of ART initiation in pregnancy was not significantly associated with odds of preterm birth, small for gestational age, or low birth weight. First-trimester initiation of ART was significantly associated with increased odds of intrauterine growth restriction in the multivariate analysis [adjusted odds ratio (aOR) = 3.78, 95% confidence interval (CI): 1.23–11.59], while first trimester PI use was associated with increased odds of IUGR in the univariate analysis only [OR = 3.24, 95% CI: 1.13–9.30]. Smoking, comorbidity, and maternal HIV RNA ≥ 50 copies/mL were independently associated with increased odds of adverse birth outcomes.

Conclusions:
WWH living in Denmark are generally well-treated during pregnancy with NRTI+PI as the most common ART regimen used in pregnancy. Initiation of ART in the first trimester may be associated with poor fetal growth. The association between ART use in pregnancy and adverse birth outcomes may partly be explained by maternal risk factors. The technology appears safe, and this can be well integrated in the programme of the midwifery education.