Does Changing Antiretroviral Therapy in the First Trimester of Pregnancy for Safety Concerns Have an Impact on Viral Suppression?

Violaine Peyronnet, MD; Josiane Warszawski, MD, PhD; Jeanne Sibiude, MD, PhD; Olivia Dialla, MCS; Agnès Bourgeois-Moine, MD; Eida Bui, MD; Caroline Simon Toulza, MD; Delphine Peretti, MD; Cécile Brunet-Cartier, MD; Véronique Avettand-Fenoel, MD, PhD; Jérôme L. Chenadec, MD, PhD; Albert Faye, MD, PhD; Roland Tubiana, MD; Laurent Mandelbrot, MD; for the ANRS EPF-French Perinatal Cohort Study


J Acquir Immune Defic Syndr. 2019;80(5):574-584. 

In This Article

Abstract and Introduction


Objective: To determine whether changing antiretroviral therapy (ART) during pregnancy because of concern about fetal risks led to poorer virological outcomes.

Methods: All pregnancies in women with HIV-1 infection enrolled in the national multicenter prospective French Perinatal cohort at 14 week gestation or more were included between January 2005 and December 2015, if the mother was on ART at conception with a plasma viral load <50 copies/mL. The reasons for a change in the ART were analyzed according to treatment guidelines at the time of the pregnancy and defined as for safety concerns in the absence of reported maternal intolerance. Virological and pregnancy outcomes were studied by survival analysis and logistic regression adjusted for a propensity score established for each patient according to baseline characteristics.

Results: Of 7079 pregnancies in the overall cohort, 1797 had ART at conception with a viral load <50 copies/mL before 14 week gestation. Of these, 22 changed regimens in the first trimester for intolerance, and 411 of the remaining 1775 (23%) solely for safety concerns. The proportion of change was higher when the initial treatment was not recommended in the national guidelines (OR adjusted: 23.1 [14.0–38.2]), than when it was an alternative option (ORa: 2.2 [1.3–3.7]), as compared to recommended first-line regimens. Treatment changes for safety concerns did not lead to poorer virological control, compared with pregnancies without such changes (19.3% vs. 15.6%, HRa: 1.0 [0.7–1.4]).

Conclusions: Changing ART early in pregnancy to regimens considered safer for pregnancy, and neonatal health did not have a destabilizing effect on viral suppression.


One of the major benefits of antiretroviral therapy (ART) is to prevent perinatal transmission,[1–9] attaining zero transmission when maternal viral load is undetectable from conception until delivery.[10] Because lifelong ART is recommended for all people living with HIV,[5] women are increasingly on treatment at the time of conception. Thus, safety issues are of crucial importance to choose which antiretrovirals to use in pregnancy. A variety of adverse events have been reported to be related to antiretroviral exposure during pregnancy, regarding the fetus and future infant, the woman herself, and pregnancy outcomes.[11–18]

For women taking medications who become, or plan to become pregnant, clinicians and patients are faced with a choice of whether or not it should be changed for safety concerns, even in the absence of intolerance or inefficacy. Recommendations are periodically updated according to the available data and interpretation of benefits and risks.[2–6] Expert panels diverge about how to take into account pregnancy-specific safety issues, for several reasons. First, there is debate over the actual risks, for instance, whether exposure to efavirenz increases the fetal malformation rate.[15,19] Second, there is debate as to whether recent medications should be avoided in pregnancy as long as safety data are lacking. Third, there is concern that switching may lead to poorer compliance or tolerance and thus virological failure, which is the main risk factor for perinatal transmission.[20,21] In France, as in many other countries, boosted protease inhibitors (PIs) associated with 2 nucleoside reverse transcriptase inhibitors (NRTIs) have been the first-line therapies for pregnant women for 2 decades, whereas WHO guidelines favor efavirenz with 2 NRTIs.[22] French guidelines[23] suggest that even in case of virological efficacy, consideration should be given to changing an ART in case of concern about potential safety risks. In many other countries, it is recommended not to change an effective treatment during pregnancy.[24,25] However, following a recent report of an increased incidence of neural tube defects associated with dolutegravir use,[26] several guidelines recommended switching from dolutegravir to other drugs in the periconceptional period.[27–29]

The objective of our study was to determine whether changing ART in pregnant women who were on effective therapy at conception had an impact on viral load and pregnancy outcomes.