The Grapevine

HIV Infection Drug Atazanavir May Negatively Affect Fetal Development If Taken By Pregnant Women

Fetal development
Although babies born to infected mothers are usually HIV-positive, with proper medication, they often become healthy and HIV-free by their first birthday. John Moore/Getty Images

Atazanavir, sold under the trade name Reyataz, is one of many antiretroviral medications (ARVs) used to treat HIV infection. This particular drug is sometimes included in regimens to prevent mother-to-child HIV transmission during pregnancy, which may not be such a good thing, finds a new study published in AIDS.

Study authors cited that using ARVs "during pregnancy has dramatically decreased the incidence of perinatal HIV transmission." And yet, despite the growing number of HIV-exposed but uninfected infants, the authors thought the estimated effects of ARV regimens required further evaluation. They aimed to estimate the effect ARV regimens, including atazanavir, had on neurodevelopment in infants aged nine to 15 months compared to all other ARV regimens.

The analysis included 917 pregnant women living with HIV already enrolled in The Surveillance Monitoring for ART Toxicities (SMARTT), a cohort of women who were not on ARVs during their last menstrual period but were during pregnancy between October 2006 and April 2013. Three ARV regimens were included: Two or more ARVs from at least two drug classes; three nucleoside reverse transcriptase inhibitors; one protease inhibitor; or one nonnucleoside reverse transcriptase inhibitor.

Study authors assessed several neonatal outcomes associated with infant development, including low birth weight, gestational age, premature birth, neonatal hearing, and head circumference in order to understand how infants were affected by ARVs in utero. When infants turned one year old, they were also given the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) test, which was designed to assess problem-solving, language, fine- and gross-motor skills, as well as social-emotional development and adaptive behavior.

Of the 282 mothers who initiated ARVs with atazanavir during their first trimester, 30 percent switched to a different regimen before delivery compared to 22 percent of mothers who initiated ARVs during the second or third trimester. And the results showed infants scored about 3.4 points lower on language and 5.9 points lower on social-emotional development only when mothers initiated their regimen during the second and third trimester. However, adverse language effects seemed to be relevant regardless of when mothers initiated their chosen regimen, the authors wrote.

How is this possible? Study authors explained ARVs "must cross the placenta to impact fetal development, and must further penetrate the fetal blood-brain barrier to have an effect on neurodevelopment." Given that atazanavir has an especially "poor transplacental passed and low central nervous system penetration," authors said they were surprised to arrive at this conclusion.

"However, the development of the blood-brain barrier is a gradual process and its integrity can be compromised by inflammation, toxins, or maternal substance abuse, especially if exposure occurs during the early stages of development," the authors added. "Another possibility is that the effect of prenatal atazanavir exposure might be mediated by hyperbilirubinemia, which has been associated with increased risk of suboptimal developmental outcomes and hearing impairment, a risk factor for delays in language and social-emotional development."

That said, the authors acknowledged their study has several limitations, most notably that atazanavir is commonly prescribed in conjunction with another ARV, tenofovir (Truvada) — 75 percent of regimens included the two ARVs together. The combination made it hard to isolate atazanavir's effects, so authors can't say definitively if ARV regimens with atazavanir alone affect fetal development.

The silver lining — if the two drugs are commonly prescribed together, then that's something to explore in future clinical practice. It may also be useful in regimen guidelines for women with HIV infection.

"A three-point difference in the Bayley-III Language domain score and a five-point difference in the Social-Emotional domain score may not have large clinical implications, but they add another risk to the constellation of existing biological and socio-environmental risk factors to which these children are often exposed," study authors concluded.

Source: Caniglia EC, et al. Atazanavir exposure in utero and neurodevelopment in infants: A comparative safety study. AIDS. 2016.

Loading...