Caution urged for expectant mothers on ritonavir-boosting regimen

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

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.”

Disclosure: Dr Warszawski reported having obtained a research grant from Abbott Laboratories for another study concerning lopinavir- ritonavir in children. Dr Polak reported having received support for educational presentations and grant support from Pfizer, IPSEN, and Sandoz-SAS Laboratories. Dr Blanche reported having received support for travel to meetings from Abbott Laboratories and honoraria for lectures and for development of educational presentations from Astellas, Boehringer Ingelheim, GlaxoSmithKline and Tibotec Laboratories.

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