Caution urged for expectant mothers on ritonavir boosting regimen

**Simon A. JAMA. 2011;doi:10.1001/jama.2011.915.**

Issue: August 2011

Mothers who have HIV and were treated before and after birth with lopinavir-ritonavir were more likely to have infants with adrenal dysfunction compared with a zidovudine-based regimen, according to a preliminary report published online this week.

Albane Simon, MD, of the Hospital Necker-Enfants Maiades, Assistance Publique-Hopitaux de Paris, and colleagues looked at mother-child pairs in the Paris area who were enrolled in the French Perinatal Cohort Study between December 2004 and September 2008. They evaluated 50 HIV-1 uninfected children who received lopinavir-ritonavir just after birth, and 108 who received standard prophylaxis: zidovudine alone (n=100), zidovudine and lamivudine (n=6), or zidovudine and nevirapine (n=2).

Among the 50 newborns treated with lopinavir-ritonavir, 14% had abnormally high hydroxyprogesterone results from dried blood spots (>16.5 ng/mL at term or >23.1 ng/mL preterm) vs. none of the controls. For children born at term, five of 42 newborns treated with lopinavir-ritonavir vs. zero of 93 controls had values of more than 16.5 ng/mL.

The median (midpoint) 17-hydroxyprogesterone (17OHP) value for term newborns treated with lopinavir-ritonavir was 9.9 ng/mL vs. 3.7 ng/mL in controls. The difference observed in median 17OHP values between treated newborns and controls was higher in children also exposed in utero (11.5 ng/mL vs. 3.7 ng/mL) than not exposed in utero (6.9 ng/mL vs. 3.3 ng/mL).

Consistent with the findings for 17OHP, the dehydroepiandrosterone sulfate values were significantly higher only in cases also exposed in utero to ritonavir-boosted protease inhibitor.

“Our findings of the association between lopinavir-ritonavir and transient adrenal dysfunction in HIV-1 uninfected newborns suggest that lopinavir-ritonavir, and more generally ritonavir-boosting, should be used with caution, if at all, in premature infants, and if this drug regimen is administered to full-term infants, it should be used under electrolyte monitoring,” the researchers concluded. “Whether more prolonged exposure of HIV-1-infected or -uninfected infants via breast milk is associated with endocrine disruption should be carefully investigated, and the apparent risk associated with prenatal ritonavir exposure also merits further evaluation.”

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