SAN FRANCISCO — Fetal and early natal exposure to antiretroviral therapy may put healthy children of women infected with the HIV at increased risk of heart disease later in life, according a study presented at the annual meeting of the Pediatric Academic Societies.
Dr. Steven E. Lipshultz reported that HIV-negative children born to mothers on antiretroviral therapy (ART) were healthier and had stronger hearts at birth than did HIV-negative children born a decade earlier to infected mothers who were not given ART. During the infants' first year of life, however, echocardiograms showed the ART-exposed children had reductions in left ventricular mass and septal wall thickness, which resulted in “serial increases in left ventricular afterload or stress on the wall of the heart.”
“Initially, there was improved left ventricular contractility and left ventricular fractional shortening,” he said. “What was concerning is there are progressive increases in left ventricular afterload, resulting in the loss of improvement in left ventricular fractional shortening.”
While the clinical significance of these changes is not yet known, they call for much better long-term care of children who escape HIV infection in the womb and are often lost to follow-up because their mothers die or the family is dysfunctional, advised Dr. Lipshultz, chairman of pediatrics at the University of Miami.
“Continued use of antiretroviral therapy to prevent mother-to-child transmission of HIV is critical,” he said, estimating more than a million children have been exposed to ART in utero. “The benefit of preventing HIV infection with ART outweighs the theoretical risk of cardiac toxicity, but [the study] points to the need to really emphasize long-term follow-up in this population.”
The prospective Cardiac Highly Active Antiretroviral Therapy (CHAART) study was sponsored by the National Heart, Lung, and Blood Institute. Dr. Lipshultz said a randomized, controlled trial was not possible, as denying ART to HIV-infected women would be unethical.
Instead, the investigators enrolled participants at the same sites where another NHLBI investigation, the Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2) study, had enrolled HIV-infected mothers from 1990 to 1994. Dr. Lipshultz and his colleagues compared serial echocardiograms for 216 unexposed P2C2 infants with those of 91 exposed infants in the CHAART study.
Among their findings was that babies born in the antiretroviral era have better heart function at birth than their predecessors did, but the difference is no longer significant by 6–12 months of age. While left ventricular afterload decreased during the first year of life in the unexposed infants, it increased in those whose mothers received ART.
“Initially, there was less stress on the heart, but with time, this really flipped, and there was about half a standard deviation more stress/higher afterload by a year of age. And that was significant,” Dr. Lipshultz said. He reported the difference in septal wall thickness was more than a standard deviation at all ages.
“We speculate that antiretroviral exposure appears to be associated with reduced myocardiac growth that may be putting these children at greater risk for subsequent cardiac problems,” Dr. Lipshultz said at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.
“In many cases, [ART-exposed children] get lost from the regular medical system,” he said. Because of limited resources, only children who are born HIV positive are apt to receive comprehensive follow-up at pediatric HIV clinics. So care of HIV-negative offspring falls to the primary care physician, he said.
'The benefit of preventing HIV infection with ART outweighs the theoretical risk of cardiac toxicity.' DR. LIPSHULTZ