The impact of HAART on cardiomyopathy among children and adolescents perinatally infected with HIV-1.
OBJECTIVE
Previous studies of cardiomyopathy among children perinatally infected with HIV were conducted before the routine use of HAART. Nucleoside analogs [nucleoside reverse transcriptase inhibitors (NRTIs)], the backbone of HAART, have been associated with mitochondrial toxicity, which can lead to cardiomyopathy. We evaluated the association of HAART and specific NRTIs associated with mitochondrial toxicity, on development of cardiomyopathy among perinatally HIV-infected children.


METHODS
Three thousand and thirty-five perinatally HIV-infected children enrolled in a US-based multicenter prospective cohort study were followed for cardiomyopathy, defined as a clinical diagnosis or initiation of digoxin, from 1993 to 2007.


METHODS
Cox models were used to estimate the effects of HAART and NRTIs on cardiomyopathy, identify predictors of cardiomyopathy among HAART users, and estimate the association between development of cardiomyopathy and mortality.


RESULTS
Ninety-nine cases of cardiomyopathy were identified over follow-up (incidence rate: 5.6 cases per 1000 person-years) at a median age of 9.4 years. HAART was associated with a 50% lower incidence of cardiomyopathy compared with no HAART use (95% confidence interval: 20%, 70%). Zalcitabine (ddC) use, however, was associated with an 80% higher incidence of cardiomyopathy. Among HAART users, older age at HAART initiation, ddC use before HAART initiation, initiating a HAART regimen containing zidovudine (ZDV), and a nadir CD4 percentage less than 15% were independently associated with a higher rate of cardiomyopathy. Cardiomyopathy was associated with a six-fold higher mortality rate.


CONCLUSIONS
HAART has dramatically decreased the incidence of cardiomyopathy among perinatally HIV-infected children. However, they remain at increased risk for cardiomyopathy and ongoing ZDV exposure may increase this risk.
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. kpatel@hsph.harvard.edu
Kunjal
K
Patel
Russell B
RB
Van Dyke
Murray A
MA
Mittleman
Steven D
SD
Colan
James M
JM
Oleske
George R
GR
Seage
D000293:Adolescent; D019380:Anti-HIV Agents / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004077:Digoxin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006679:HIV Seropositivity / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000706:statistics & numerical data*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000188:drug therapy* / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D016047:Zalcitabine / Q000009:adverse effects*; D015215:Zidovudine / Q000009:adverse effects*
D019380:Anti-HIV Agents; D002316:Cardiotonic Agents; D015215:Zidovudine; D016047:Zalcitabine; D004077:Digoxin