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

Abstract

Objective To determine the cardiac effects of prolonged exposure to highly active antiretroviral therapy (HAART) on HIV-infected (HIV+) children. Design In the National Institutes of Health (NIH)-funded Pediatric HIV/AIDS Cohort Study’s Adolescent Master Protocol (AMP), we used linear regression models to compare echocardiogram measures. Setting 14 U.S. pediatric HIV clinics. Patients/Participants Perinatally-infected HIV+ children receiving HAART with HIV-exposed but uninfected (HEU) children and HIV+ (mostly HAART-unexposed) historical pediatric controls from the NIH-funded Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2-HIV) Study. Main Exposure Long-term HAART. Outcome Measures Echocardiographic measures of left ventricular (LV) function and structure. Results The 325 AMP HIV+ children had lower viral loads, higher CD4 counts, and longer duration of antiretroviral therapy than 70 P2C2 HIV+ children (all P’s < 0·001). Z scores for LV fractional shortening (a measure of cardiac function) were significantly lower among P2C2 HIV+ children than among the AMP HIV+ group or the 189 AMP HEU controls (P < 0.05). For HIV+ children, lower nadir CD4 percentage and higher current viral load were associated with significantly lower cardiac function (LV contractility and LV fractional shortening Z scores; P’s = 0.001) and increased LV end-systolic dimension Z score (P’s < 0.03). In an interaction analysis by HIV+ cohort, P2C2 HIV+ children with longer ART exposure or lower nadir CD4 percentage had lower mean LV fractional shortening Z scores, while mean Z scores were relatively constant among AMP HIV+ children (P<0·05 for all interactions). Conclusions HAART appears to be cardioprotective in HIV+ children and adolescents.

Association of Human Immunodeficiency Virus Infection with Exposure to Highly Active Antiretroviral Therapy and Its Adverse Cardiovascular Effects

“…Left ventricular dilation may precede heart failure (5-year cumulative incidence, 12.3%) and is associated with elevated LV afterload, LV hypertrophy, and reduced LV function. 77 Early and continuous treatment with HAART for at least five years prevented clinically important heart failure in HIV-infected children better than in earlier groups and preserved cardiac structure and function, indicating that HAART may be cardioprotective. 77 Both the PHACS and CHAART studies suggest that any cardiac changes in the HAART era are generally subclinical in children.…”

“…33,69,75,77 HIV-infected patients post-MI have similar short-term outcomes but increased readmission for congestive heart failure at a one-year follow up. 81 Clinical Presentation Concurrent pulmonary infections, anemia, pulmonary hypertension, malnutrition, portal hypertension, and malignancy can change or confuse the distinctive signs in HIV-infected patients that otherwise define heart failure in other populations.…”

“…76 Among pre-HAART-era HIV-infected children 10 years of age or younger, 25% died from chronic cardiac disease 5,6 and 28% experienced serious cardiac events after an AIDS-defining illness. 1,5,6,77 Only in children has a mild decrease in LV systolic function or an increase in LV mass been predictive of mortality. 25 The National Heart, Lung, and Blood Institute (NHLBI) funded the Highly Active Antiretroviral Therapy-Associated Cardiotoxicity (CHAART-II) study, which collected longitudinal echocardiographic measurements of HIV-infected children and adolescents exposed to HAART or multidrug ART.…”

Perinatally infected adolescents living with human immunodeficiency virus (perinatally human immunodeficiency virus)

“…Increasing numbers of children with vertically transmitted HIV infection are reaching adulthood and, thus, becoming chronically ill adults [27] . In addition to its impact on the survival of this population, prolonged HAART also seems to have cardioprotective effects in HIV-infected children and adolescents [29] . However, as part of this scenario of improved survival, many youths develop severe metabolic complications, including lipodystrophy, dyslipidemia, insulin resistance, lactic acidosis, and bone mass loss.…”

Resolution of dilated cardiomyopathy in an adolescent with change of a failing highly active antiretroviral drug therapy

“…Left ventricular function at baseline has been found to be a risk factor for death that is independent of the CD4 count, HIV viral load and neurological disease 2 . Long term HAART is cardioprotective for HIV infected children and adolescents 5 , and reduces the risk of cardiomyopathy by 50% in children compared to those not on HAART 6.…”