Author + information
- Received March 28, 2017
- Revision received August 8, 2017
- Accepted September 6, 2017
- Published online October 23, 2017.
- Steven E. Lipshultz, MDa,b,∗ (, )
- James D. Wilkinson, MD, MPHa,
- Bruce Thompson, PhDc,
- Irene Cheng, MSc,
- David A. Briston, MDd,
- William T. Shearer, MD, PhDe,
- E. John Orav, PhDf,
- Joslyn A. Westphal, MPHa,
- Tracie L. Miller, MDg,
- Steven D. Colan, MDh,
- for the CHAART-2 Investigator Group
- aWayne State University School of Medicine, Detroit, Michigan
- bChildren’s Hospital of Michigan, Detroit, Michigan
- cTheta Hat Statistical Consultants, Owings Mills, Maryland
- dOhio State University Medical Center and Nationwide Children’s Hospital, Columbus, Ohio
- eBaylor College of Medicine and Texas Children’s Hospital, Houston, Texas
- fBrigham and Women’s Hospital, Boston, Massachusetts
- gUniversity of Miami Miller School of Medicine, Miami, Florida
- hBoston Children’s Hospital, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Steven E. Lipshultz, Department of Pediatrics, Wayne State University School of Medicine, 3901 Beaubien Boulevard, Pediatric Administration-T121A, Detroit, Michigan 48201.
Background Before the introduction of highly active antiretroviral therapy (HAART), cardiac mortality and morbidity were common in HIV-infected children.
Objectives This study sought to identify long-term cardiovascular effects of HAART in HIV-infected children.
Methods The CHAART-2 (HAART-Associated Cardiotoxicity in HIV-Infected Children) study prospectively compared 148 echocardiograms from 74 HAART-exposed children to 860 echocardiograms from 140 HAART-unexposed but HIV-infected children from the Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) study. Both studies used similar protocol, centralized echocardiographic interpretation, and measures expressed as z-scores referenced to healthy controls. Associations between HAART exposure and echocardiographic measures were evaluated using generalized estimating equations.
Results Comparing the HAART-exposed and HAART-unexposed groups, any HAART exposure was positively associated with left ventricular (LV) fractional shortening (z-score for difference = 1.07; p = 0.02) and HAART exposure duration (z-score difference per year = 0.17; p = 0.003. LV mass was negatively associated with any HAART exposure (z-score difference = −0.64; p = 0.01) as was septal thickness (z-score difference = −0.93; p = 0.001). Duration of HAART exposure was negatively associated with LV end-systolic dimension and heart rate (z-score difference per year= −0.11; p = 0.05; and z-score difference per year = −0.10; p = 0.002, respectively). During 11 years of follow-up, in the HAART-exposed group, LV mass and LV end-diastolic septal thickness were lower whereas LV contractility and LV fractional shortening were higher when compared to the HAART-unexposed group.
Conclusions Cardiac structure and function were better in perinatally HIV-infected children exposed to HAART than in those of similar children from the pre-HAART era but did decline over time. Evidence-based strategies for cardiovascular monitoring are needed to inform treatment decisions to improve long-term cardiovascular health.
The CHAART-2 study was supported by grant R01 HL078522 from the National Heart, Lung, and Blood Institute (SEL). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received March 28, 2017.
- Revision received August 8, 2017.
- Accepted September 6, 2017.
- 2017 American College of Cardiology Foundation