Absence of cardiac toxicity of zidovudine in infants. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection Study Group.
ABSTRACT Perinatal exposure to zidovudine may cause cardiac abnormalities in infants. We prospectively studied left ventricular structure and function in infants born to mothers infected with the human immunodeficiency virus (HIV) in order to determine whether there was evidence of zidovudine cardiac toxicity after perinatal exposure.
We followed a group of infants born to HIV-infected women from birth to five years of age with echocardiographic studies every four to six months. Serial echocardiograms were obtained for 382 infants without HIV infection (36 with zidovudine exposure) and HIV-58 infected infants (12 with zidovudine exposure). Repeated-measures analysis was used to examine four measures of left ventricular structure and function during the first 14 months of life in relation to zidovudine exposure.
Zidovudine exposure was not associated with significant abnormalities in mean left ventricular fractional shortening, end-diastolic dimension, contractility, or mass in either non-HIV-infected or HIV-infected infants. Among infants without HIV infection, the mean fractional shortening at 10 to 14 months was 38.1 percent for those never exposed to zidovudine and 39.0 percent for those exposed to zidovudine (mean difference, -0.9 percent; 95 percent confidence interval, -3.1 percent to 1.3 percent; P=0.43). Among HIV-infected infants, the mean fractional shortening at 10 to 14 months was similar in those never exposed to zidovudine (35.4 percent) and those exposed to the drug (35.3 percent) (mean difference, 0.1 percent; 95 percent confidence interval, -3.7 percent to 3.9 percent; P=0.95). Zidovudine exposure was not significantly related to depressed fractional shortening (shortening of 25 percent or loss) during the first 14 months of life. No child over the age of 10 months had depressed fractional shortening.
Zidovudine was not associated with acute or chronic abnormalities in left ventricular structure or function in infants exposed to the drug in the perinatal period.
SourceAvailable from: Lynne M Mofenson[Show abstract] [Hide abstract]
ABSTRACT: j , for the Pediatric HIV/AIDS Cohort Study (PHACS) Objectives: We evaluated the potential cardiac effects of in-utero exposures to anti-retroviral drugs in HIV-exposed but uninfected (HEU) children. Design and methods: We compared echocardiographic parameters of left ventricular function (ejection fraction, fractional shortening, and stress–velocity index) and struc-ture (left ventricular dimension, posterior wall/septal thickness, mass, thickness-to-dimension ratio, and wall stress) (expressed as Z-scores to account for age and body surface area) between HEU and HIV-unexposed cohorts from the Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring for ART Toxicities study. Within the HEU group, we investigated the associations between the echocardiographic Z-scores and in-utero exposures to maternal antiretroviral drugs. Results: There were no significant differences in echocardiographic Z-scores between 417 HEU and 98 HIV-unexposed children aged 2–7 years. Restricting the analysis to HEU children, first-trimester exposures to combination antiretroviral therapy (a regimen including at least three antiretroviral drugs) and to certain specific antiretroviral drugs were associated with significantly lower stress–velocity Z-scores (mean decreases of 0.22–0.40 SDs). Exposure to combination antiretroviral therapy was also associated with lower left ventricular dimension Z-scores (mean decrease of 0.44 SD). First-trimester exposure to combination antiretroviral therapy was associated with higher mean left ventricular posterior wall thickness and lower mean left ventricular wall stress Z-scores. Conclusion: There was no evidence of significant cardiac toxicity of perinatal com-bination antiretroviral therapy exposure in HEU children. Subclinical differences in left ventricular structure and function with specific in-utero antiretroviral exposures indicate the need for a longitudinal cardiac study in HEU children to assess long-term cardiac risk and cardiac monitoring recommendations.AIDS 01/2015; 29:91-100. DOI:10.1097/QAD.0000000000000499 · 6.56 Impact Factor
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ABSTRACT: Objective To determine the occurrence of cardiac involvement in HIV infected children and describe its spectrum using non-invasive tests like ECG and 2-Dimensional Echocardiography (2-D ECHO). Methods A cross sectional observational study was carried out on 100 HIV infected children between 1 and 18 y of age. The various cardiac manifestations were determined clinically, by electrocardiogram (ECG) and 2-D echocardiography. Results Seventy four percent of the patients were males with a mean age of 9.62 ± 3.62 y. Seventy seven percent children were in WHO stage I. Sixty five percent did not have significant immune suppression. Eighty six percent children were on HAART (mean duration- 35.12 ± 29.48 mo). Fifty nine percent of children were symptomatic and only nine patients were clinically suspected to have cardiac involvement. ECG abnormalities were found in 14 % cases. The most common abnormal echocardiographic finding was left ventricular diastolic dysfunction by tissue Doppler (E/E′) observed in 64 % cases followed by systolic dysfunction (37 %), abnormal left ventricular mass (29 %), pericardial effusion (2 %) and dilated cardiomyopathy (2 %); 64.2 % cases with left ventricular systolic dysfunction (LVSD) were in WHO stage III. Conclusions Involvement of heart in HIV/AIDS is mostly subclinical. HIV myocarditis produces systolic as well as diastolic dysfunction. At present, echocardiography remains the only tool for identifying heart involvement in HIV-infected children. Early diagnosis and intervention may halt the progression of the disease, thereby preventing morbidity and mortality.The Indian Journal of Pediatrics 05/2014; 82(3). DOI:10.1007/s12098-014-1481-9 · 0.92 Impact Factor
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ABSTRACT: IMPORTANCE Prior to contemporary antiretroviral therapies (ARTs), children infected with human immunodeficiency virus (HIV) were more likely to have heart failure. This study suggests that highly active ART (HAART) does not appear to impair heart function. OBJECTIVE To determine the cardiac effects of prolonged exposure to HAART on HIV-infected children. DESIGN In the National Institutes of Health-funded Pediatric HIV/AIDS Cohort Study's Adolescent Master Protocol (AMP), we used linear regression models to compare echocardiographic measures. SETTING A total of 14 US pediatric HIV clinics. PARTICIPANTS Perinatally HIV-infected children receiving HAART (n = 325), HIV-exposed but uninfected children (n = 189), and HIV-infected (mostly HAART-unexposed) historical pediatric controls from the National Institutes of Health-funded Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2-HIV) Study (n = 70). EXPOSURE Long-term HAART. MAIN OUTCOMES AND MEASURES Echocardiographic measures of left ventricular (LV) function and structure. RESULTS The 325 AMP HIV-infected children had lower viral loads, higher CD4 counts, and longer durations of ART than did the 70 HIV-infected children from the P2C2-HIV Study (all P < .001). The z scores for LV fractional shortening (a measure of cardiac function) were significantly lower among HIV-infected children from the P2C2-HIV Study than among the AMP HIV-infected group or the 189 AMP HIV-exposed but uninfected controls (P < .05). For HIV-infected children, a lower nadir CD4 percentage and a higher current viral load were associated with significantly lower cardiac function (LV contractility and LV fractional shortening z scores; all P = .001) and an increased LV end-systolic dimension z score (all P < .03). In an interaction analysis by HIV-infected cohort, the HIV-infected children from the P2C2-HIV Study with a longer ART exposure or a lower nadir CD4 percentage had lower mean LV fractional shortening z scores, whereas the mean z scores were relatively constant among AMP HIV-infected children (P < .05 for all interactions). CONCLUSIONS AND RELEVANCE Long-term HAART appears to be cardioprotective for HIV-infected children and adolescents.04/2013; 167(6):1-8. DOI:10.1001/jamapediatrics.2013.1206