Antiretroviral Therapy During Pregnancy Can Increase Risk of Childhood Neurologic Abnormalities

By Brian Hoyle

SAN FRANCISCO -- October 9, 2018 -- The use of antiretroviral therapy, particularly efavirenz, during pregnancy appears to pose a risk of neurologic abnormalities early in the life of the child, according to a study presented here at ID Week 2018, the 56th Annual Meeting of the Infectious Diseases Society of America (IDSA).

“In utero efavirenz exposure was associated with a higher risk of neurologic abnormalities in infancy and childhood. There was a suggestion of an association between in utero dolutegravir exposure and these higher risks,” said Claudia Crowell, MD, MPH, Seattle Children’s Hospital, Seattle, Washington, in a Late Breaker session.

The primary outcome of the Surveillance Monitoring for ART Toxicities (SMARTT) study was what the researchers termed a “neurologic case,” which included microcephaly, febrile seizures, seizure disorders, ophthalmologic disorders, and other neurologic conditions as determined in a blinded clinical review. The association of antiretroviral exposure during pregnancy with these outcomes was evaluated in patients treated during the first half of 2017 compared with women with HIV who did not receive antiretroviral therapy.

Of the 3,747 children evaluated (52% male, 68% black, 31% Hispanic), 237 were judged to have neurologic abnormalities, representing a rate of 6.3% (95% confidence interval [CI], 5.6-7.2). Use of tobacco and alcohol during pregnancy was common (17% and 8%, respectively). Almost all (98%) of the children had been exposed to antiretroviral drugs in utero, including protease inhibitor (70%), nonnucleoside reverse transcriptase inhibitor (19%, with efavirenz used in 4.5% of the cases), and integrase strand transfer inhibitor (11%, with dolutegravir used in 2.6% of the cases).

After adjustment for several confounding factors, a trend was seen toward an association of neurologic abnormalities and HIV treatment with efavirenz (adjusted relative risk [aRR], 1.60; 95% CI, 0.99-2.58) and treatment with dolutegravir (aRR, 2.17; 95% CI, 0.69-6.89. Further sensitivity analyses determined that the significance of efavirenz was maintained when focused on infants and children <2 years of age (aRR, 1.87; 95% CI, 1.06-3.05), when children with confirmed congenital anomalies were excluded (aRR, 1.64; 95% CI, 1.02-2.64), and for the incidence over time (aRR, 1.66; 95% CI, 1.00-2.76). Significant associations for dolutegravir were lost in the sensitivity analyses.

Antiretroviral therapy for pregnant women with HIV has been very effective in lessening perinatal transmission of the virus. However, this good news has come with lingering concern of treatment-related adverse neurologic outcomes. These latest findings can only heighten this concern.

Limitations of the study include its observational design, low numbers of children exposed to newer antiretrovirals, and the clinical implications of the findings.

Funding for the study was provided by the National Institutes of Health.
[Presentation title: In Utero Antiretroviral (ARV) Exposure: Neurologic Outcomes in HIV-Exposed, Uninfected Children. Abstract LB5]
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