Cardiac Effects of Antiretroviral Therapy in HIV-Negative Infants Born to HIV-Positive Mothers

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.

Memory CD4+CCR5+ T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1

“…1,2 However, exposure to cART in utero and postnatally can have long-term adverse effects in these HIV-1-exposed, uninfected children. [3][4][5][6][7] A better understanding of MTCT is crucial for the development of targeted and safe prevention strategies. However, the actual mechanism of MTCT remains unclear.…”

Cardiac Status of Children Infected With Human Immunodeficiency Virus Who Are Receiving Long-term Combination Antiretroviral Therapy

“…The impact of HIV infection and ART in children suggests that sub-clinical abnormalities of cardiac structure and function may eventually result in symptomatic cardiomyopathy in adulthood as they are exposed to the other cardiovascular risk factors listed above. 1,3–11,24–26 …”

Effects of Zidovudine Treatment on Heart mRNA Expression and Mitochondrial DNA Copy Number Associated with Alterations in Deoxynucleoside Triphosphate Composition in a Neonatal Rat Model

“…Clearly, further in vivo studies must be conducted to establish a dose-response analysis. Shortterm (7)(8)(9)(10)(11)(12)(13)(14) and long-term (15)(16)(17)(18) problems associated with AZT treatment in neonatal animal models and humans have been noted by others and are described in the introduction. It has been previously shown that alterations in dNTP composition are associated with mutagenesis in nuclear and mitochondrial DNA (23,26) and may account for the long-term problems (15)(16)(17)(18) and reports of AZT-induced carcinogenicity (15).…”

“…Anemia and myelosuppression were also noted in noninfected infants of HIV-positive mothers who were treated with AZT (7). Additionally, AZT treatment has been shown to induce cardiotoxicity in children, as echocardiographs from a cohort of HIV-negative children revealed a significant decrease in left ventricular mass, left ventricular dimension, and septal wall thickness, which may impair myocardial growth (8). Eccentric left ventricle hypertrophy was seen in an AZT-treated HIV-1 transgenic mouse model (9).…”