HIV Prevention in Neonates May Cause Transient Adrenal Insufficiency: An In Vivo and in Vitro Study

Presentation Number: SUN 397
Date of Presentation: April 2nd, 2017

Tanja Christa Haamberg*1, Jana Malikova1, Ralph Fingerhut2, Susanna Sluka2, Jane McDougall1 and Christa E. Fluck1
1Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland, 2University Children's Hospital of Zurich, Zurich, Switzerland

Abstract

Background: HIV drugs Lopinavir and Ritonavir have been reported to cause transient adrenal insufficiency in preterm newborns. We report a preterm baby with elevated 17-hydroxyprogesterone (17OHP) in newborn screening, who had no signs of congenital adrenal hyperplasia (CAH). After birth the girl was treated with Zidovudine for prevention of vertical HIV transmission, while the HIV positive mother was treated with Atripla (Efavirenz, Tenofovir, Emtricitabin) during pregnancy. So far, the effect of HIV drugs on steroidogenesis in general and on 21-hydroxylase enzyme activity specifically have not been tested in vitro. This study aimed to close this gap.

Methods: Effects of Efavirenz, Tenofovir, Emtricitabin, Zidovudine were tested on steroidogenesis in adrenal H295R cells. Cells were treated with pur substances at (supra-) therapeutical concentrations for 3 and 24 hours. The 21-hydroxylase activity was assassed by looking at the conversion of labelled [3H] 17-hydroxyprogesterone to 11-deoxycortisol using thin layer chromatography. Cell viability was tested by an MTT essay.

Results: Efavirenz decreased 21-hydroxalyse activity significantly in cells treated with therapeutical concentrations. Only Efavirenz also decreased cell viability at supratherapeutical concentrations. By contrast, all other drugs did not affect steroidogenesis. Follow-up of the patient revealed elevated 17OHP and androgens during the first weeks of life, but normalized spontaneously at around one month of life suggesting a transient effect. Genetic testing for CYP21A2 mutations was negative.

Conclusion: Treatment with Efavirenz seems to affect steroidogenesis at concentrations in clinical use. Case reports on other HIV preventive drugs suggest that HIV drugs may cause transient adrenal insufficiency resulting in pathologic neonatal screening for CAH. Thus neonates treated with HIV preventive drugs may be at risk for adrenal crisis in emergency situations.

 

Nothing to Disclose: TCH, JM, RF, SS, JM, CEF