HIV transmission to infants from mothers that are treated during pregnancy is below one percent these days, but this week it is reported that when HIV positive moms are treated with the combination of lopinavir-ritonavir, infants are experiencing more incidence of adrenal dysfunction.
The adrenal glands are small but very powerful glands that sit atop each of your kidneys located in the middle of your back. They are really two separate organs combined into one location; the outer portion acalled the adrenal cortex and the inner portion called the adrenal medulla. The focus of this text is on the adrenal cortex.
The cortex serves primarily a hormonal function, and among the main functions of the adrenal cortex are the regulation of the mineral metabolism (sodium, potassium, chloride), water balance, metabolism (utilization and distribution of carbohydrates, protein, and fat), allergic and immune reactions (such as hypersensitivity, allergies, and autoimmune diseases), and production of the male and female hormones (progesterone, testosterone, estrogens, DHEA, etc.).
Lopinavir-ritonavir is licensed in the United States for HIV-infected newborns older than 14 days and in Europe for children older than 2 years. However, published data concerning its use in newborns are scarce.
The Journal of the Medical Association article states:
“The HIV-l transmission rate to newborns is now less than 1% for women treated during pregnancy. For pregnant women not optimally treated, as in cases of HIV diagnosis late during pregnancy or persistent viral replication at delivery, several guidelines, observational reports, and the results of a recent controlled study suggest reinforcing the postnatal phase of treatment with a combination of anti-retrovirals, as a ‘postexposure prophylaxis.’ The protease inhibitor lopinavir, with its pharmacological booster ritonavir (lopinavir-ritonavir), is now the ritonavir-boosted protease inhibitor most widely prescribed in children.”
In April 2010, one of the centers of the French national screening program for congenital adrenal hyperplasia (CAH; a group of inherited disorders of the adrenal glands) identified a transient increase of 17-hydroxyprogesterone (17OHP; a steroid hormone produced mainly by the adrenal glands) in dried blood spots from 2 children treated at birth with lopinavir-ritonavir.
The study continues:
“All term newborns treated with lopinavir-ritonavir were asymptomatic, although 3 premature newborns experienced life-threatening symptoms compatible with adrenal insufficiency, including hyponatremia (abnormally low level of sodium in the blood) and hyperkalemia, (higher than normal levels of potassium in the circulating blood; associated with kidney failure) with in 1 case, cardiogenic shock. All symptoms resolved following completion of the lopinavir-ritonavir treatment. In summary, 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. 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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Written by Sy Kraft