Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published January 25, 2023


What are some of the factors that have made it difficult to define the effects of ART on pregnancy outcomes?

Vertical transmission of human immunodeficiency virus (HIV) is essentially eliminated in non–breast-feeding persons who have sustained viral suppression. The main questions pertain to which antiretroviral therapy (ART) regimens have the best safety and side-effect profiles when used during pregnancy. Read the NEJM Review Article here.

Clinical Pearls

Q: Do pregnant persons with HIV generally receive the newest, most desirable ART regimens?

A: As improved regimens are adopted in the general population, guidelines for ART during pregnancy are evolving. ART regimens currently recommended during pregnancy include two nucleoside reverse-transcriptase inhibitors in combination with ART from a different class (classified as “preferred or recommended” or “alternative” in pregnancy). However, because of the absence or delayed availability of pharmacokinetic and safety data associated with the use of ART during pregnancy, recommendations for ART often lag behind guidelines for nonpregnant adults living with HIV. As a result, pregnant persons often receive older, less desirable regimens.

Q: What are some of the factors that have made it difficult to define the effects of ART on pregnancy outcomes?

A: Challenges remain in our understanding of adverse pregnancy outcomes related to ART use during pregnancy. The greatest limitation is that pregnancy studies either are not done at all or are completed years after drug registration. Analyses of the effect of the timing of ART initiation in pregnancy are susceptible to selection bias, and confounders are often inadequately controlled for in observational studies. Large numbers of ART exposures are needed to detect differences in low-frequency end points. Background rates of adverse birth outcomes vary markedly among populations, time periods, and settings, making comparisons with background rates challenging to interpret in observational studies. In addition, end point definitions vary among studies, and gestational age is not accurately determined in the absence of fetal ultrasonography.

Morning Report Questions 

Q: Are efavirenz (EFV) and dolutegravir (DTG) contraindicated during pregnancy?

A: EFV and DTG deserve special mention. Early nonhuman primate studies suggested the possibility of central nervous system malformations with EFV, but large cohort studies and antiretroviral pregnancy registries have not shown this association in humans. Concern about a possible early signal of an increase in neural-tube defects with DTG-based ART from a birth surveillance system in Botswana was first reported in 2019. However, as more data were analyzed, the prevalence of neural-tube defects with periconception DTG exposure declined and is now similar to that in the general population. As a result of concern regarding congenital anomalies with EFV and DTG, pregnant persons have been denied EFV and DTG regimens that were both safer and more effective than older regimens, highlighting the need for the establishment of surveillance systems to rapidly provide pregnant persons with high-quality data so that they can make informed decisions.

Q: Do the known benefits of ART in pregnant persons outweigh potential adverse outcomes?

A: The known benefits of ART in pregnant persons living with HIV for optimizing maternal and infant health and preventing transmission of HIV to the infant clearly outweigh potential adverse outcomes. Newer ART regimens are associated with better pregnancy outcomes than the older antiretroviral agents. For these reasons, pregnant persons should start or continue treatment with preferred or alternative ART regimens that result in adequate viral suppression and are associated with an acceptable adverse-effect profile. The data on most of the newer ART regimens remain reassuring, but pharmacovigilance should be maintained.

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