SAN FRANCISCO — Children were 60% more likely to be diagnosed with a neurologic condition, such as microcephaly, seizures, or eye abnormalities, when the antiretroviral regimen their mothers were taking during pregnancy included efavirenz (Sustiva, Bristol-Myers Squibb), new data show.
This is a single study, and more will be needed to better guide clinicians, investigator Claudia Crowell, MD, from Seattle Children’s Hospital and the University of Washington, cautioned during a news conference here at IDWeek 2018.
The children will continue to be followed so that the long-term effects can be assessed, she reported.
“The pendulum has swung back and forth over the years regarding efavirenz use in pregnancy because of concern about potential teratogenicity,” said Gail Shust, MD, a from Hassenfeld Children’s Hospital at NYU Langone Health in New York City, who was not involved with the study.
Currently, the US Food and Drug Administration advises against the use of efavirenz in women of childbearing potential. However, the US Department of Health and Human Services and the World Health Organization suggest that efavirenz can be used throughout pregnancy.
“It will be interesting to see how this study affects these recommendations,” Shust told Medscape Medical News. In the meantime, providers should recommend antiretroviral regimens with the most safety data, she added.
Monitoring for ART Toxicities
In their study, Crowell and her colleagues examined 3747 HIV-exposed uninfected children enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study conducted by the Pediatric HIV/AIDS Cohort Study network, which follows children to determine the long-term effects of antiretroviral medications taken during pregnancy.
Of the 3747 children studied, 52% were male, 68% were black, and 31% were Hispanic. The average age of the 237 children in the cohort diagnosed with a neurologic condition was 2 years.
Sixteen babies with neurologic conditions were born to mothers who had taken efavirenz. Babies were more likely to be diagnosed with a neurologic condition if their mothers took efavirenz than if they did not (absolute risk, 9.6% vs 6.2%).
The relative risk for neurologic conditions with efavirenz was 1.60 (95% confidence interval [CI], 0.99 - 2.58) after adjustment for potential confounders, such as Hispanic heritage, tobacco use during pregnancy, and birth before or after 2011.
The association between neurologic conditions and efavirenz was statistically significant when sensitivity analyses were limited to children enrolled before or shortly after birth (adjusted relative risk [RR], 1.80; 95% CI, 1.06 - 3.05), when children with confirmed congenital anomalies were excluded (adjusted RR, 1.66; 95% CI, 1.02 - 2.64), and when person-time follow-up was accounted for (adjusted RR, 1.55; 95% CI, 1.00 - 2.76).
The data presented have special meaning in light of the dolutegravir news that emerged after the drug had been widely rolled out in resource-limited settings, said Jeanne Marrazzo, MD, from the University of Alabama at Birmingham, who is chair of the HIV medicine association division for IDWeek.
A recent study conducted in Botswana (N Engl J Med. 2018;379:979-981) showed “a potential early signal for an increased prevalence of neural-tube defects in association with dolutegravir-based antiretroviral therapy from the time of conception,” she explained.
“In the absence of feeling safe about dolutegravir, a lot of people have reverted to saying we can probably use efavirenz,” Marrazzo told Medscape Medical News.
Although the new data on efavirenz are not definitive, they are concerning enough that “we can’t just default to efavirenz and feel like it’s going to be okay,” she pointed out.
The real message is that “we don’t have great nonprotease-inhibitor-based regimens for pregnant women, especially in developing countries where options are going to be limited,” she noted.
One important thing to note about the Botswana study is that the risk was for women exposed to dolutegravir at the time of conception, said Eric Daar, MD, from Harbor–UCLA Medical Center in Torrance, California.
“So the problem isn’t just what we give women who are pregnant,” he pointed out. “What do we give women who aren’t reliably using contraception and have reproductive potential?” Good data on antiretroviral options are very limited, he added.
As the number of women of childbearing potential living with HIV — in Europe, the United States, and in resource-limited settings — continues to increase, the issue of which antiretroviral therapy is best and safest is gaining prominence, he explained.
Some of the study investigators report receiving research support from Gilead Sciences and stock dividends from Abbott Labs and AbbVie. Crowell, Shust, and Marrazzo have disclosed no relevant financial relationships. Daar reports receiving research support from Gilead, Merck, and ViiV.
IDWeek 2018: Abstract LB5. Presented October 4, 2018.
By Marcia Frellick
- Infectious Diseases Society of America: Antiretroviral therapy with efavirenz in HIV-positive pregnant women likely increases risk of neurological condition in children
- Healio: Efavirenz exposure increases risk of neurological conditions in infants