Cardiac Effects of Antiretroviral Therapy in HIV-Negative Infants Born to HIV-Positive Mothers
Key result
Fetal antiretroviral exposure is linked to lower infant LV mass Z-scores alongside increased contractility.
- MD -0.46
- P=0.005
- n=352
Why the study?
Does in utero exposure to antiretroviral therapy affect cardiac development and function in HIV-negative infants born to HIV-positive mothers?
Key Points
- To evaluate the long-term effects of in utero antiretroviral therapy exposure on myocardial structure and cardiac function in HIV-negative infants up to 24 months of age.
- Prospective multi-site cohort study comparing serial echocardiograms obtained between birth and 24 months.
- Included 352 HIV-negative infants born to HIV-positive mothers: 136 exposed to antiretroviral therapy (ART+) and 216 unexposed (ART−).
- Mean left ventricular (LV) mass Z-scores were significantly lower in ART+ girls than ART− girls at birth (-0.46, P=0.005), 6 months (-1.02, P<0.001), 12 months (-0.74, P<0.001), and 24 months (-0.79, P<0.001), with smaller differences observed in boys.
- Infants exposed to ART had reduced septal wall thickness and LV dimensions alongside consistently higher LV contractility of approximately 1 standard deviation at all ages (P<0.001) and increased LV fractional shortening, particularly in girls.
Study Design
Type
Cohort (n=352)
Multicenter
Yes
Structured PICO
Does in utero exposure to antiretroviral therapy affect cardiac development and function in HIV-negative infants born to HIV-positive mothers?
P
Population
352 HIV-negative infants born to HIV-positive mothers (136 exposed to ART in utero, 216 unexposed) followed from birth to 24 months.
E
Exposure
In utero exposure to antiretroviral therapy (ART)
C
Comparator
No in utero exposure to antiretroviral therapy
O
Outcome
Cardiac development and function measured by echocardiograms (LV mass Z-scores, septal wall thickness, LV dimension, LV contractility, LV fractional shortening) between birth and 24 monthssurrogate
Main Result
Mean Difference: -0.46
p-value: p=0.005
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“That finding was concerning because it suggested that these antiretrovirally-exposed but uninfected children may be at risk as they get older of developing heart failure from diastolic heart dysfunction of the main pumping chamber of the heart, the left ventricle”
“These medicines have been very effective at reducing the rate of transmission of HIV from mother to child, but the findings we've just published show clearly that further investigation of their long-term impact on the heart health of the children involved is needed.”
“The lack of information about the long-term safety of drugs prescribed for children is a special worry, both for drugs that may be used for decades for chronic conditions and for drugs for which short-term use may be found to harm children's growth and development months or years later. Although these are effective medicines for children, in order to understand their safety, long-term pediatric safety studies are needed to potentially allow future options for improvement if serious safety risks are identified.”
Implication
In utero exposure to ART in HIV-negative infants is associated with altered myocardial growth and increased LV contractility up to age 2 years, with more pronounced effects in girls.
Abstract
Objective To investigate the possible effects of antiretroviral therapy (ART) in utero on cardiac development and function in 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 multi-site cohort study design, we compared echocardiograms taken between birth and 24 months in two groups of HIV-negative infants of HIV-positive mothers: 136 infants exposed to ART (ART+) and 216 unexposed infants (ART−). Results Mean 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. Conclusion 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.
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Cite This Study
Lipshultz et al. (2010) conducted a cohort in HIV-negative infants of HIV-positive mothers (n=352). Antiretroviral therapy (ART) in utero vs. Unexposed infants (ART-) was evaluated on Mean LV mass Z-scores in girls at birth (MD -0.46, p=0.005). Fetal exposure to antiretroviral therapy was associated with reduced LV mass Z-scores in girls at birth (mean difference -0.46, P=0.005) and up to 24 months, alongside increased LV contractility.