Two Studies Shed More Light on Adverse Pregnancy Outcomes of Antiretroviral Therapy

NIAID Now | January 25, 2019

Women with HIV are at risk of infecting their children during pregnancy, during birth, or shortly thereafter. US and World Health Organization (WHO) guidelines recommend the use of a three-drug regimen of antiretroviral therapy (ART) during pregnancy to reduce the risk of mother-to-child transmission to less than 1%. This recommendation was based on numerous observational studies showing that the use of a three-drug cocktail including the anti-HIV drugs tenofovir and emtricitabine during pregnancy was safe. However, recent results from the NIAID-sponsored Promoting Maternal and Infant Survival Everywhere (PROMISE) trial identified potential safety concerns. Women randomly assigned to receive tenofovir, emtricitabine, and lopinavir had infants at greater risk of very premature birth or death within 14 days of delivery.

To better understand the safety of exposure to various ART regimens during pregnancy, NIAID-funded researchers analyzed data on pregnant HIV-infected women collected from two US-based studies. The women received one of three common three-drug ART regimens: tenofovir, emtricitabine, and lopinavir; tenofovir, emtricitabine and atazanavir; or zidovudine, lamivudine, and lopinavir. Overall, women in the three groups had similar risks of having infants born prematurely or with low birthweight. An analysis of the women who started treatment before conception suggested that those who were treated with tenofovir, emtricitabine, and lopinavir/ritonavir had an increased risk of preterm birth compared to the other two ART regimens.

A few other studies have suggested that becoming pregnant while on ART may lead to similar harmful outcomes. An increasing number of women are conceiving while on ART, as the treatment guidelines now recommend starting treatment immediately after diagnosis of HIV infection.

To examine this issue, NIAID-supported investigators reviewed data from a large clinical trial in which HIV-infected women who were treated during pregnancy were randomly assigned to either continue or stop ART after giving birth. The investigators examined the effects on the outcomes of a subsequent pregnancy, including spontaneous abortion and stillbirth. The women assigned to continue ART had higher rates of spontaneous abortion and stillbirth. However, these results did not hold up when comparing women who actually were or were not on ART, as not all women adhered to the prescribed regimen. Previous studies have provided conflicting data regarding whether ART affects the rate of stillbirths. Further studies are needed to explore pregnancy outcomes among women who conceive on ART, particularly with newer drug regimens. Such studies will inform decisions on how to balance the relatively low risks of adverse pregnancy outcomes against the benefits of lifelong, uninterrupted ART.


Rough K et al. Birth Outcomes for Pregnant Women with HIV Using Tenofovir-Emtricitabine. New England Journal of Medicine. 2018 Apr 26; 378:1593–1603.

Hoffman RM et al. Adverse Pregnancy Outcomes Among Women Who Conceive on Antiretroviral Therapy. Clinical Infectious Diseases. 2019 Jan 7; 68:273–279.

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