The antiretroviral therapy (ART) regimen associated with the least risk of adverse birth outcomes among pregnant women with HIV, relative to other regimens, is tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV), according to a new study.

“Our results provide reassurance for the more than 90% of HIV-infected women who live in countries that follow WHO recommendations to use TDF-FTC-EFV,” wrote Rebecca Zash, MD, of Beth Israel Deaconess Medical Center in Boston and her associates in JAMA Pediatrics.

“Our results also suggest that HIV infection and ART may play a more important role in adverse birth outcomes than was previously recognized and could help explain the lack of significant improvement in stillbirth and neonatal death rates throughout sub-Saharan Africa during the past 2 decades,” the investigators wrote (JAMA Pediatrics. 2017 Aug 7. doi: 10.1001/jamapediatrics.2017.2222 ).

Using data collected from August 2014 through August 2016, the researchers compared outcomes among 47,027 births by women from Botswana, average age 26 years, who reached at least 24 weeks’ gestation. The study’s data came from eight government hospitals throughout Botswana, where approximately 45% of births had occurred nationwide.

The 11,932 infants exposed to HIV, representing about a quarter of all infants in the study, had a higher risk of adverse birth outcomes: 39.6% of HIV-exposed infants had adverse outcomes, compared with 28.9% of unexposed infants.

Nearly half (48.4%) of the HIV-exposed infants had also been exposed to ART from conception. Among these 5,780 infants, those exposed to the ART regimen comprising tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV) had the lowest rate of adverse birth outcomes. The following percentages of infants exposed to different ART regimens had adverse outcomes:

The risk of adverse birth outcomes, compared with exposure to TDF-FTC-EFV, was 15% higher for TDF-FTC-NVP, 21% higher for ZDV-3TC-LPV-R, 30% higher for ZDV-3TC-NVP, and 31% higher for TDF-FTC-LPV-R after researchers adjusted for age and potential sociodemographic confounders.

The risk of severe adverse outcomes for ART exposure from conception was as follows:

The risk for giving birth to an infant small for gestational age was lowest for TDF-FTC-EFV, compared with the other regimens.

“Differences between TDF-FTC-EFV and other ART regimens were greater for small for gestational age than for preterm birth,” suggesting a “drug-specific mechanism at the placental level because the health of the placenta is directly related to fetal growth,” the researchers wrote. “An ART effect at the level of the placenta may also explain why women receiving ART before conception have more adverse outcomes than [do] those who start ART after conception because endothelial dysfunction during placentation would be expected to have a more detrimental effect on the pregnancy,” they added.

The ZDV-3TC-NVP regimen was linked to greater risk for stillbirth, very preterm birth, and neonatal death; the ZDV-3TC-LPV-R regimen was linked to a greater risk of preterm and very preterm birth, as well as neonatal death.

“Our study findings may be difficult to integrate into settings with ART regimen choices beyond those available in Botswana,” the authors wrote. “Whether the magnitude of the differences we found in Botswana will be similar in higher-resource settings is unclear.”

The research was funded by the National Institutes of Health. The authors reported no conflicts of interest.