Cardiac effects of antiretroviral therapy in HIV-negative infants born to HIV-positive mothers: NHLBI CHAART-1 (National Heart, Lung, and Blood Institute Cardiovascular Status of HAART Therapy in HIV-Exposed Infants and Children cohort study)

Abstract

Objectives: The aim of this study was to investigate the possible effects of antiretroviral therapy (ART) in utero on cardiac development and function in human immunodeficiency virus (HIV)-negative children.

Background: ART reduces vertical HIV transmission. Long-term cardiotoxicity after in utero exposure to ART is unknown in children but has occurred in young animals.

Methods: Using a prospective multisite cohort study design, echocardiograms taken between birth and 24 months were compared in 2 groups of HIV-negative infants of HIV-positive mothers: 136 infants exposed to ART (ART+) and 216 unexposed infants (ART-).

Results: Mean left ventricular (LV) mass z-scores were consistently lower in ART+ girls than in ART- girls: differences in mean z-scores were -0.46 at birth (p = 0.005), -1.02 at 6 months (p < 0.001), -0.74 at 12 months (p < 0.001), and -0.79 at 24 months (p < 0.001). Corresponding differences in z-scores for boys were smaller: 0.13 at 1 month (p = 0.42), -0.44 at 6 months (p = 0.01), -0.15 at 12 months (p = 0.37), and -0.21 at 24 months (p = 0.21). Septal wall thickness and LV dimension were smaller than expected in ART+ infants, but LV contractility was consistently about 1 SD higher at all ages (p < 0.001). In ART+ infants, LV fractional shortening was higher than in ART- infants; girls showed a greater difference.

Conclusions: Fetal exposure to ART is associated with reduced LV mass, LV dimension, and septal wall thickness z-scores and increased LV fractional shortening and contractility up to age 2 years. These effects are more pronounced in girls than in boys. Fetal ART exposure may impair myocardial growth while improving depressed LV function.

Figure 1. Cardiac Measurements of 136 CHAART-1 Infants and 216 P²C²-HIV Infants

CHAART-1 ART-positive infants' data are shown by the blue line with hollow boxes. P²C²-HIV ART-negative infants' data are shown by the red line with solid boxes. Rectangles show interquartile ranges, and vertical lines show the 5^th percentile to the 95^th percentile. Dots represent outliers. (LV=left ventricular; FS=fractional shortening; EDD=end-diastolic dimension; ESD=end-systolic dimension; ED SWT=end-diastolic septal wall thickness)

Figure 1. Cardiac Measurements of 136 CHAART-1 Infants and 216 P²C²-HIV Infants

CHAART-1 ART-positive infants' data are shown by the blue line with hollow boxes. P²C²-HIV ART-negative infants' data are shown by the red line with solid boxes. Rectangles show interquartile ranges, and vertical lines show the 5^th percentile to the 95^th percentile. Dots represent outliers. (LV=left ventricular; FS=fractional shortening; EDD=end-diastolic dimension; ESD=end-systolic dimension; ED SWT=end-diastolic septal wall thickness)

Figure 2. Cardiac and Anthropomorphic Measurements of 136 CHAART-1 Infants and 216 P²C²-HIV Infants

CHAART-1 ART-positive infant data are shown by the blue line with hollow boxes. P²C²-HIV ART-negative infant data are shown by the red line with solid boxes. Rectangles show interquartile ranges, and vertical lines show the 5^th percentile to the 95^th percentile. Dots represent outliers. (LV=left ventricular; ED PWT=end-diastolic posterior wall thickness; ES PWT=end-systolic posterior wall thickness; ES SWT=end-systolic septal wall thickness; BP=blood pressure)