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Efavirenz exposure increases risk of neurological conditions in infants

Children who were exposed to efavirenz in utero to prevent HIV transmission from their infected mother were 60% more likely to acquire a neurological condition compared with children exposed to other regimens, according to research presented at IDWeek 2018.

Claudia S. Crowell, MD, MPH, assistant professor of pediatrics at the University of Washington and Seattle Children’s Hospital, told Infectious Diseases in Children that the study’s aim was to assess the long-term safety of fetal and infant exposure to different regimens of prophylactic ART.

“Efavirenz is not a part of the first-line, recommended regimen for use in pregnant women or in nonpregnant adults in general mainly because it is associated with pretty significant neuropsychiatric side effects,” Crowell said. “There are other antiretroviral medications that have higher barriers to resistance and better side effect profiles that are considered first-line therapy. However, if a woman is already on an efavirenz-containing regimen, tolerating it well and is virally suppressed, then the current recommendations are to just keep her on that during pregnancy."

She added that although efavirenz is not the first-line therapy for pregnant women in the United States, the medication is part of WHO's recommended regimen for use during pregnancy. According to Crowell, this is because efavirenz has not demonstrated that it increases the risk for birth defects, “so it is thought to be pretty safe for use in pregnancy.”

To further explore the effects of ART regimens during pregnancy, the researchers assessed the outcomes of children enrolled in a longitudinal observational cohort study run by the Pediatric HIV/AIDS Cohort Study network. Specifically, Crowell and colleagues analyzed the frequency of neurologic cases, including microcephaly, febrile seizures, seizure disorders, ophthalmologic disorders and other neurologic conditions.

The researchers identified 3,747 eligible children who were exposed to HIV but were uninfected. Of these children, 237 had diagnosed neurologic conditions (6.3%; 95% CI, 5.6%-7.2%). Mothers of these children frequently exposed their infants to tobacco (17%) and alcohol (8%) while pregnant, and 98% of children were exposed to ART.

pregnant woman 
Source: Adobe

When Crowell and colleagues examined specific ART regimens, 70% of mothers used protease inhibitor-based medications, and 19% used non-nucleoside reverse transcriptase inhibitor-based medications, like those containing efavirenz.

The researchers observed that children exposed to efavirenz were more likely to have a neurological condition (adjusted RR = 1.6; 95% CI, 0.99-2.58) compared with children exposed to other ART regimens. When participants were limited to those enrolled in the study before or shortly after birth and those without confirmed congenital abnormalities, this relationship became statistically significant.

In previous research, efavirenz-containing ART regimens created a threefold increased risk for suicidality among ART-naive patients.

“It is a little unclear at this point — since this is a single observational study — whether this could be replicated in other studies, so it is important that long-term follow-up be conducted in other cohorts as well," Crowell said. “It is also unclear at this point what the long-term clinical implications of some of these diagnoses are. We will continue to follow our cohort to answer that question, but for now, our results do not suggest that we need to make a change in our guidelines or clinical practice at this time.” – by Katherine Bortz

Reference:

Crowell CS, et al. Abstract LB5. Presented at: IDWeek 2018; Oct. 3-7, 2018; San Francisco.

Disclosures: Crowell reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Children who were exposed to efavirenz in utero to prevent HIV transmission from their infected mother were 60% more likely to acquire a neurological condition compared with children exposed to other regimens, according to research presented at IDWeek 2018.

Claudia S. Crowell, MD, MPH, assistant professor of pediatrics at the University of Washington and Seattle Children’s Hospital, told Infectious Diseases in Children that the study’s aim was to assess the long-term safety of fetal and infant exposure to different regimens of prophylactic ART.

“Efavirenz is not a part of the first-line, recommended regimen for use in pregnant women or in nonpregnant adults in general mainly because it is associated with pretty significant neuropsychiatric side effects,” Crowell said. “There are other antiretroviral medications that have higher barriers to resistance and better side effect profiles that are considered first-line therapy. However, if a woman is already on an efavirenz-containing regimen, tolerating it well and is virally suppressed, then the current recommendations are to just keep her on that during pregnancy."

She added that although efavirenz is not the first-line therapy for pregnant women in the United States, the medication is part of WHO's recommended regimen for use during pregnancy. According to Crowell, this is because efavirenz has not demonstrated that it increases the risk for birth defects, “so it is thought to be pretty safe for use in pregnancy.”

To further explore the effects of ART regimens during pregnancy, the researchers assessed the outcomes of children enrolled in a longitudinal observational cohort study run by the Pediatric HIV/AIDS Cohort Study network. Specifically, Crowell and colleagues analyzed the frequency of neurologic cases, including microcephaly, febrile seizures, seizure disorders, ophthalmologic disorders and other neurologic conditions.

The researchers identified 3,747 eligible children who were exposed to HIV but were uninfected. Of these children, 237 had diagnosed neurologic conditions (6.3%; 95% CI, 5.6%-7.2%). Mothers of these children frequently exposed their infants to tobacco (17%) and alcohol (8%) while pregnant, and 98% of children were exposed to ART.

pregnant woman 
Source: Adobe

When Crowell and colleagues examined specific ART regimens, 70% of mothers used protease inhibitor-based medications, and 19% used non-nucleoside reverse transcriptase inhibitor-based medications, like those containing efavirenz.

The researchers observed that children exposed to efavirenz were more likely to have a neurological condition (adjusted RR = 1.6; 95% CI, 0.99-2.58) compared with children exposed to other ART regimens. When participants were limited to those enrolled in the study before or shortly after birth and those without confirmed congenital abnormalities, this relationship became statistically significant.

In previous research, efavirenz-containing ART regimens created a threefold increased risk for suicidality among ART-naive patients.

“It is a little unclear at this point — since this is a single observational study — whether this could be replicated in other studies, so it is important that long-term follow-up be conducted in other cohorts as well," Crowell said. “It is also unclear at this point what the long-term clinical implications of some of these diagnoses are. We will continue to follow our cohort to answer that question, but for now, our results do not suggest that we need to make a change in our guidelines or clinical practice at this time.” – by Katherine Bortz

Reference:

Crowell CS, et al. Abstract LB5. Presented at: IDWeek 2018; Oct. 3-7, 2018; San Francisco.

Disclosures: Crowell reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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