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Antiretroviral Therapy May Have Protective Effect on HIV+ Children's Hearts

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Long-term use of combination antiretroviral therapy (ART) does not impair heart function in children and adolescents with perinatal HIV infection, and in fact appears to have a "cardioprotective" effect, according to a study published in the April 22, 2013, advance online edition of JAMA Pediatrics.

 

In the early years of the HIV/AIDS epidemic, before the advent of effective treatment, children with HIV had higher rates of heart failure and related problems compared with uninfected children. But this may no longer be the case if the era of highly active antiretroviral therapy, or HAART.

Steven Lipshult and fellow investigators with the Pediatric HIV/AIDS Cohort Study conducted a study to evaluate the cardiac effects of prolonged exposure to HAART among HIV-infected children and adolescents.

The analysis included 325 perinatally infected children at 14 U.S. pediatric HIV clinics receiving combination ART, 189 HIV-exposed but uninfected children, and 70 historical controls from a prior study who had HIV but mostly were not exposed to HAART.

The researchers found that LV fractional shortening -- a measure of cardiac function -- was significantly lower among HAART-treated HIV-infected children than among untreated or exposed but uninfected children.

"Our results indicate that the current use of combination ART, usually HAART, appears to be cardioprotective in HIV-infected children and adolescents," they wrote. "This finding is even more relevant in the developing world where the prevalence of HIV disease in children is much higher."

Below is an edited excerpt from a National Institutes of Health press release describing the study and its findings in more detail.

Anti-HIV Therapy Appears to Protect Children's Hearts, NIH Network Study Shows

April 22, 2013 -- For children who have had HIV-1 infection since birth, the combination drug therapies now used to treat HIV appear to protect against the heart damage seen before combination therapies were available, according to researchers in a National Institutes of Health network study.

In the early 1990s, children with HIV were not treated with anti-HIV therapy or were treated with only one drug. In recent years, children, like adults, have been treated with combinations of three or more anti-HIV medications. This combination approach is called highly active antiretroviral therapy, or HAART.

Before the widespread use of HAART [highly active antiretroviral therapy], many children with HIV had chronic heart disease. In fact, heart failure was the underlying cause of death for 25% of HIV-infected children who died after age 10. However, doctors knew little about whether combination anti-HIV drug therapies could affect the heart.

In this study, researchers examined heart structure and function of more than 500 children born to HIV-infected mothers. They then compared the data with results from the National Heart, Lung, and Blood Institute (NHLBI)-sponsored Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection study of HIV-infected children, conducted in the 1990s.

"The NIH has been committed to investigating the effects of HIV and its treatment on the heart," said study co-author Rohan Hazra, MD, of the Maternal and Pediatric Infectious Disease Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), one of ten NIH institutes or offices that supported the study. "Our study indicates that anti-HIV medication may protect the heart."

First author Steven E. Lipshultz, MD, of the University of Miami Miller School of Medicine, and his colleagues collaborated with Dr. Hazra and colleagues at the NHLBI in Bethesda, Md.; as well as with investigators at Harvard University in Boston; Tulane University in New Orleans; Baylor College and Texas Children’s Hospital in Houston; University of Illinois at Chicago; Frontier Science Technology and Research Foundation in Amherst, N.Y.; and Boston Children’s Hospital.

Their findings appear online in JAMA Pediatrics.

The research was conducted as part of the Pediatric HIV/AIDS Cohort Study (PHACS), which receives support from the NICHD, NHLBI, National Institute of Allergy and Infectious Diseases, National Institute of Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse and the Office of AIDS Research.

The 500 children in the PHACS study were between 7 and 16 years old. Although all had been exposed to HIV before birth, some were HIV-infected and some remained HIV-uninfected. The HIV-infected children in the current study had, on average, received anti-HIV medications for at least twice as long as children in the study conducted in the 1990s. Roughly 80% of the children in the PHACS study were treated with HAART for five years or longer. Although 17% of the children in the earlier study received some HAART treatment, none had received HAART for as long as five years.

Researchers measured heart structure and function with echocardiography, a technique that uses sound waves to generate images of the heart. When comparing the echocardiograms among the children who took part in the current study, the researchers found that the hearts of the HIV-infected children were generally slightly less healthy than those of their HIV-uninfected counterparts.

About 45% of the children in the 1990s study had an enlarged heart or substantial damage to the heart muscle. In the HAART group, only 4% had heart damage.

"We know that before today's robust treatments were available, HIV-positive children were more likely to have heart infections and inflammation; many also died from heart failure," said Dr. Lipshultz. "This research followed a rigorous protocol, and the findings suggest that HAART, in addition to being good for treating HIV, does not appear to adversely affect the heart’s function."

About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s website at http://www.nichd.nih.gov.

About the National Institutes of Health (NIH)

NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

4/24/13

Reference

SE Lipshultz, PL Williams, JD Wilkinson, et al (Pediatric HIV/AIDS Cohort Study (PHACS). Cardiac Status of Children Infected With Human Immunodeficiency Virus Who Are Receiving Long-term Combination Antiretroviral Therapy: Results From the Adolescent Master Protocol of the Multicenter Pediatric HIV/AIDS Cohort Study. JAMA Pediatrics. April 22, 2013 (Epub ahead of print).

Other Sources

National Institutes of Health. Anti-HIV Therapy Appears to Protect Children's Hearts, NIH Network Study Shows. Press release. April 22, 2013.

JAMA. Highly Active Antiretroviral Therapies May Be Cardioprotective in HIV-Infected Children, Teens. Media Advisory for April 22, 2013.