Use of Antiretroviral Therapy in Pregnancy and Association With Birth Outcome Among Women Living With HIV in Denmark

A Nationwide, Population-Based Cohort Study

Ellen Moseholm; Terese Lea Katzenstein; Gitte Pedersen; Isik Somuncu Johansen; Lisa Skyggelund Wienecke; Merete Storgaard; Niels Obel; Nina Weis

Disclosures

HIV Medicine. 2022;23(9):1007-1018. 

In This Article

Abstract and Introduction

Abstract

Objective: To describe antiretroviral therapy (ART) regimens during pregnancy among women living with HIV (WLWH) in Denmark and to examine the association between ART use in pregnancy and adverse birth outcomes.

Methods: A population-based cohort study including all pregnancies among WLWH in Denmark between 2000 and 2019. Data were collected through national registries. Temporal trends of ART use in pregnancy were evaluated. Logistic regression models were used to examine the association of ART use in pregnancy and other risk factors with adverse birth outcomes.

Results: In total, 589 pregnancies were included. Combination treatment with a nucleoside reverse transcriptase inhibitor (NRTI) and a protease inhibitor (PI) was the most common ART regimen (96%). ART regimen, PI use in pregnancy and timing of ART initiation were not significantly associated with increased 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: Pregnant WLWH living in Denmark are generally well treated with HIV RNA < 50 copies/mL at delivery and 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.

Introduction

Antiretroviral therapy (ART) is recommended worldwide for all people with HIV, including pregnant women.[1] As a result, an increasing number of women living with HIV (WLWH) will either conceive or start treatment during pregnancy. The success of ART in combination with changing recommendations has resulted in a decreased risk of perinatal transmission to < 1% in Denmark and other high-income countries,[2,3] leading to a growing population of HIV-exposed, uninfected (HEU) children.[4] From a treatment perspective, pregnant women are a special population, largely because of the opportunity to prevent perinatal transmission of HIV and the need to consider the safety of the women themselves and their exposed foetuses and children.[5]

No single antiretroviral (ARV) regimen has consistently been considered first-line for pregnant women, and recommended regimens and indications for some ARV drugs have changed over time as more potent and tolerable drugs have become available.[6] European guidelines currently recommend universal HIV testing of pregnant women, immediate initiation of treatment with a combination of three or more ARV drugs from at least two drug classes (combination ART), and continuation of treatment if the woman is already taking ART prior to pregnancy.[7]

It has been widely debated whether in utero exposure to HIV and/or ARVs may be associated with an increased risk of adverse birth outcomes. Several studies have reported a higher risk of preterm birth (PTB),[8,9,10] low birth weight (LBW),[8,10,11] and small for gestational age (SGA)[11] among neonates born to WLWH compared with neonates born to women without HIV (WWOH). Other studies have not been able to confirm these findings.[12,13,14] The timing of ART seems to be important and several studies have reported an increased risk of adverse birth outcomes among WLWH with pre-conception ART compared with WLWH who started ART in pregnancy.[8,11,15] However, this risk may differ depending on the specific ART regimen.[16] The use of protease inhibitors (PIs) during pregnancy has been associated with PTB,[15,17] particularly regimens that include lopinavir/ritonavir.[15,18]

Using data from the Danish HIV Birth Cohort (DHBC), we previously reported a higher prevalence of PTB, intrauterine growth restriction (IUGR) and LBW among children born to WLWH compared with children born to WWOH in Denmark.[19,20,21] In this nationwide, population-based cohort study, we aimed to describe ART regimens during pregnancy among WLWH in Denmark, including regimen changes during pregnancy, and to examine the association of ART use in pregnancy and other risk factors with different adverse birth outcomes.

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