Treatment of newborns with anti-AIDS drug Kaletra can cause adrenal problems. (Paula Bronstein )
Using the anti-AIDS drug Kaletra prophylactically in newborn infants of HIV-positive women may cause potentially life-threatening adrenal problems in some of the infants, French researchers reported Tuesday. Although no deaths have been reported from such use, the routine prophylactic use of the drug should probably be discontinued, particularly because other effective drugs are also available, the team reported in the Journal of the American Medical Assn.
About 1% of HIV-positive women now deliver an infant who is also HIV-positive. But many HIV-negative newborns are routinely treated with HIV drugs to ensure against infection.
Kaletra, manufactured by Abbott Laboratories of Abbott Park, Ill., is a combination of the anti-AIDS drugs lopinavir and ritonavir. Lopinavir is a protease inhibitor, one of the most powerful classes of HIV drugs, and ritonavir is used to boost its efficacy. The combination is approved in the United States for treatment of children over the age of 14 days and in Europe for children over the age of 2. In March of this year, the U.S. Food and Drug Administration warned that an oral solution of the drug used to treat HIV infections in newborns could cause serious heart, kidney or breathing problems. Those problems were linked to the combination of alcohol and propylene glycol in which the drug is dissolved, and the agency warned against using it in infants younger than 14 weeks. A possible cardiac toxicity of the drug has also been reported in two sets of twins born to mothers treated with the drug.
France has a program for routine screening for congenital adrenal hyperplasia based on measuring levels of a compound called 17OHP in dried blood samples collected from newborns. Congenital adrenal hyperplasia, or CAH, is a group of inherited disorders of the adrenal glands. In girls, symptoms include abnormal menstrual periods, excessive hair, a deep voice and ambiguous genitals. In boys, symptoms include a deep voice, heavy musculature, an enlarged penis and small testicles. Both sexes have normal height as children, but are unusually short as adults. The disorder is characterized by excessive production of the hormone 17-hydroxyprogesterone (17OHP) and above-normal levels of dehydroepiandrosterone-sulfate (DHEA-S), a steroid produced primarily by the adrenal cortex.
A team headed by Dr. Albane Simon of the Hopital Necker-Enfants Malades, Assistance Publique-Hopitaux de Paris evaluated blood spots from 50 HIV-negative infants who received Kaletra after birth and compared them to spots from 108 infants who had received other drugs, including zidovudine, lamivudine and nevirapine. Among those receiving Kaletra, seven (14%) had abnormally high 17OHP levels, but none of those treated with the other drugs had abnormally high 17OHP levels. Levels of 17OHP were highest in those infants whose mothers had been treated with Kaletra during the pregnancy. The team also found unusually high levels of DHEA-S in the infants treated with Kaletra, with the highest levels again in those whose mothers had received the drug during pregnancy. All of the infants who were delivered full-term were asymptomatic, the researchers said, but three of them who were delivered prematurely experienced life-threatening conditions compatible with adrenal insufficiency, including abnormally low levels of sodium in the blood (hyponatremia), higher than normal levels of potassium (hyperkalemia, associated with kidney failure) and cardiogenic shock. All the symptoms resolved when treatment with Kaletra was stopped, but the long-term effects are unknown.
The results indicate that the drug should be used in newborns rarely, if at all, the authors said. But if it is used, the infants' electrolytes should be carefully monitored for early signs of problems.