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Liver Enzyme Elevation in Pregnant Women Receiving Antiretroviral Therapy in the ANRS-French Perinatal Cohort

Sibiude, Jeanne, MD, PhDa,b; Warszawski, Josiane, MD, PhDb,c; Tubiana, Roland, MDd,e,f; Le Chenadec, Jérôme, PhDb; Meier, Françoise, MDg; Faye, Albert, MD, PhDh,i; Blanche, Stéphane, MD, PhDj,k; Mandelbrot, Laurent, MD, PhDb,i,l the ANRS-French Perinatal Cohort Study Group

JAIDS Journal of Acquired Immune Deficiency Syndromes: May 1, 2019 - Volume 81 - Issue 1 - p 83–94
doi: 10.1097/QAI.0000000000001963
Clinical Science

Background: High rates of liver enzyme elevation (LEE) in women receiving antiretroviral treatment (ART) during pregnancy have been reported, but causes remain unclear. We estimated the prevalence and risk factors of LEE in a national prospective multicenter cohort.

Methods: We studied 5748 pregnant women living with HIV enrolled in the French Perinatal Cohort 2005–2014, treated with ART, with no active hepatitis B or C coinfection. Adjusted hazard ratio (aHR) was estimated using Cox models with ART as time-dependent variable, separately for women on ART at conception and those initiating ART during pregnancy.

Results: LEE (grade ≥ 1) was observed in 16.7%, grade 3–4 in 2%. Among women with LEE, 6.7% had pre-eclampsia, 9.8% intrahepatic cholestasis of pregnancy, and 1.4% other identified medical causes. Most LEEs (82.2%) were unexplained. In women with unexplained LEE, LEE was the reason for hospitalization in 51 (6%) women, cesarean section in 13 (2%), induction of labor in 3 (0.4%), and change in ART regimen in 49 (6%) women. Unexplained LEE was associated with higher risk of preterm births, P < 0.001. Among women on ART at conception, the risk of unexplained LEE was lower with NNRTI-based regimens than with PI-based regimens: aHR = 0.5 (0.3–0.7), with no difference among the PI drugs. Most women initiating ART during pregnancy were on a PI-based regimen (89%). Among them, LEE was less frequent for women on nelfinavir vs. lopinavir/r [aHR = 0.4 (0.2–0.8)].

Conclusions: Rates of LEE among pregnant women living with HIV are high and impact obstetrical care management. The possible role of PIs needs further investigation.

aDepartment of Obstetrics and Gynecology, APHP-Hôpital Louis Mourier, Colombes, France;

bDepartment of Epidemiology, Centre de Recherche en Épidémiologie et Santé des Populations, Institut National de la Santé et de la Recherche Médicale (INSERM) U1018, Le Kremlin-Bicêtre, France;

cINED, Univ Paris Sud, Le Kremlin-Bicêtre, France;

dDepartment of Infectiology, APHP-GH Pitié Salpétrière, Paris, France;

eSorbonne Universités, UPMC Univ, Paris, France;

fINSERM-UMR_S 1136 Pierre Louis Institute of Epidemiology and Public Health, Paris, France;

gDepartment of Infectiology, APHP-Hôpital Louis Mourier, Colombes, France;

hDepartment of Pediatrics, AP-HP Hôpital Robert Debré, Paris, France;

iUniv Diderot Paris 7, Paris, France;

jProfessor, Department of Pediatrics, Hôpital Necker, Paris, 75015 France;

kEA 7223: Évaluation Thérapeutique et Pharmacologie Périnatale et Pédiatrique, Univ Paris Descartes 5, Paris 75006, France; and

lDepartment of Obstetrics and Gynecology, AP-HP, Hôpital Louis Mourier, Colombes, France.

Correspondence to: Jeanne Sibiude, MD, PhD, Equipe VIH/Pédiatrie/Reproduction CESP, 1018 Inserm, 82 rue du Général Leclerc, Le Kremlin-Bicêtre 94276, France (e-mail:

J.W. has received support from ViiV Healthcare, Parexel for past studies on pharmacovigilance, and from Abbvie, which provided drugs for the PRIMEVA trial. This work was supported by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS). ANRS is an autonomous agency at Inserm. The ANRS functions as promotor and funding and had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. J.S. received a grant from ANRS [No. 14055] and from AIDS Healthcare Foundation for this work.

Presented at CROI 2016; 22–25 February, 2016; Boston, MA, available at

The authors have no funding or conflicts of interest to disclose.

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Complete list of author names of ANRS-French Perinatal Cohort Study Group are listed in Appendix 1.

Received February 04, 2018

Accepted December 03, 2018

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