Cardiac status of children infected with human immunodeficiency virus who are receiving long-term combination antiretroviral therapy: results from the Adolescent Master Protocol of the Multicenter Pediatric HIV/AIDS Cohort Study
Steven E Lipshultz, Paige L Williams, James D Wilkinson, Erin C Leister, Russell B Van Dyke, William T Shearer, Kenneth C Rich, Rohan Hazra, Jonathan R Kaltman, Denise L Jacobson, Laurie B Dooley, Gwendolyn B Scott, Nicole Rabideau, Steven D Colan, Pediatric HIV/AIDS Cohort Study (PHACS), William Shearer, Mary Paul, Norma Cooper, Lynette Harris, Murli Purswani, Mahboobullah Baig, Anna Cintron, Ana Puga, Sandra Navarro, Doyle Patton, Deyana Leon, Sandra Burchett, Nancy Karthas, Betsy Kammerer, Margaret Ann Sanders, Kathleen Malee, Scott Hunter, Molly Nozyce, Janet Chen, Latreca Ivey, Maria Garcia Bulkley, Mitzie Grant, Katherine Knapp, Kim Allison, Megan Wilkins, Midnela Acevedo-Flores, Heida Rios, Vivian Olivera, Margarita Silio, Medea Jones, Patricia Sirois, Stephen Spector, Kim Norris, Sharon Nichols, Elizabeth McFarland, Emily Barr, Robin McEvoy, Arry Dieudonne, Linda Bettica, Susan Adubato, Gwendolyn Scott, Patricia Bryan, Elizabeth Willen, Steven E Lipshultz, Paige L Williams, James D Wilkinson, Erin C Leister, Russell B Van Dyke, William T Shearer, Kenneth C Rich, Rohan Hazra, Jonathan R Kaltman, Denise L Jacobson, Laurie B Dooley, Gwendolyn B Scott, Nicole Rabideau, Steven D Colan, Pediatric HIV/AIDS Cohort Study (PHACS), William Shearer, Mary Paul, Norma Cooper, Lynette Harris, Murli Purswani, Mahboobullah Baig, Anna Cintron, Ana Puga, Sandra Navarro, Doyle Patton, Deyana Leon, Sandra Burchett, Nancy Karthas, Betsy Kammerer, Margaret Ann Sanders, Kathleen Malee, Scott Hunter, Molly Nozyce, Janet Chen, Latreca Ivey, Maria Garcia Bulkley, Mitzie Grant, Katherine Knapp, Kim Allison, Megan Wilkins, Midnela Acevedo-Flores, Heida Rios, Vivian Olivera, Margarita Silio, Medea Jones, Patricia Sirois, Stephen Spector, Kim Norris, Sharon Nichols, Elizabeth McFarland, Emily Barr, Robin McEvoy, Arry Dieudonne, Linda Bettica, Susan Adubato, Gwendolyn Scott, Patricia Bryan, Elizabeth Willen
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.
Conflict of interest statement
Conflict of Interest Disclosures: None reported. Word count: 3022/3000
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Source: PubMed