In Utero Antiretroviral Exposure Potentially Linked to Neurological Abnormalities

Efavirenz exposure (EVF) in utero is being linked to higher risk of neurologic abnormalities in infants and children.

Efavirenz exposure (EVF) in utero is being linked to higher risk of neurologic abnormalities in infants and children. The association was made through a study by the Pediatric HIV/AIDS Cohort Study (PHACS) network that analyzed antiretroviral (ARV) medication exposure and possible adverse neurologic outcomes.


ARV therapy for pregnant women with HIV has dramatically decreased preinatal transmission of HIV, according to researchers, but concerns regarding adverse neurologic outcomes from possible mitochondrial dysfunction or other mechanisms in children exposed to in utero ARV medications remain. The Surveillance Monitoring for ART Toxicities (SMARTT) study’s primary outcome of interest was a “neurologic case,” as determined by clinical review blinded to ARV exposure.


Results of the study were presented Thursday at the ID Week conference in San Francisco.

According to researcher Claudia Crowell, MD, MPH, an infectious disease specialist at Seattle Children’s Hospital and the University of Washington, Seattle, WA, investigators found that 237 of the 3,747 HIV-exposed uninfected (HEU) children included in SMARTT study were diagnosed with neurologic conditions, yielding an event rate of 6.3% (95% CI: 5.6%, 7.2%). Among the neurologic conditions analyzed were microcephaly, febrile seizures, seizure disorders, and ophthalmologic disorders, as well as others.

The majority of children had in utero ARV exposure (87%); 60% to PI-based regimens, 16% to NNRTI-based regimens and 7% to PI + NNRTI-based regimens. In adjusted models, there was a trend towards an association between EFV and neurologic case status (aRR: 1.60, 95% CI: 0.99, 2.58). This association was statistically significant in sensitivity analyses restricted to children enrolled prior to or shortly after birth (aRR: 1.80, 95% CI: 1.06, 3.05), excluding children with confirmed congenital anomalies (aRR: 1.66, 95% CI: 1.02, 2.64), and accounting for person-time follow-up (aIRR: 1.55, 95% CI: 1.00, 2.76).


One of the most common neurologic condition diagnoses was microephaly, Crowell said, during a press conference on Thursday. She noted that although study results suggest microephaly may be linked to dolutegravir, the association shown in the SMARTT study was small. “It’s a single study, and we need further study in larger cohorts,” Crowell said.

According to Eric Daar, MD, a vice chair for ID Week and HIVMA, Harbor-UCLA Medical Center, Torrance, CA, dolutegravir’s potential impact on pregnancies has raised concerns in recent years. Earlier this year, the FDA and the European Medicines Association issued a safety alert for dolutegravir

after neural tube birth defects, including spina bifida, were reported in babies born to women with HIV being treated with the drug.


“(Those reports) have reignited an interest in how ARV affects babies,” said Daar.

Crowell noted that the SMARTT study did not determine the best regimen to use during pregnancy. “It’s important that we continue to study (medication) safety and pregnancy,” said Crowell.

This article was originally published on Pharmacy Times.


  • Crowell C. Williams, P. Yildirim C. et al. Safety of In Utero Antiretroviral (ARV) Exposure: Neurologic Outcomes in HIV-Exposed, Uninfected Children. ID Week website. Accessed October 4, 2018.
  • Coppock K. FDA Issues Safety Alert for Drug Linked to Potential Birth Defects. Pharmacy Times. Published May 19, 2018. Accessed October 4, 2018.

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