Antiretroviral Treatment in Pediatric HIV Infection in the United States
From Clinical Trials to Clinical Practice
- Susan Brogly, PhD;
- Paige Williams, PhD;
- George R. Seage III, ScD;
- James M. Oleske, MD, MPH;
- Russell Van Dyke, MD;
- Kenneth McIntosh, MD;
- for the PACTG 219C Team
- Author Affiliations: Center for Biostatistics in AIDS Research (Drs Brogly, Williams, and Seage), and Departments of Biostatistics (Drs Brogly and Williams) and Epidemiology (Dr Seage), Harvard School of Public Health, Boston, Mass; Department of Pediatrics, University of Medicine & Dentistry of New Jersey, Newark (Dr Oleske); Department of Pediatrics, Tulane University Health Sciences Center, New Orleans, La (Dr Van Dyke); and Division of Infectious Diseases, Children’s Hospital Boston, Boston, Mass (Dr McIntosh).
- Corresponding Author: Susan Brogly, PhD, Center for Biostatistics in AIDS Research, Harvard School of Public Health, 651 Huntington Ave, FXB-607, Boston, MA 02115-6017 (sbrogly{at}sdac.harvard.edu).
Abstract
Context Antiretroviral therapy (ART) for pediatric human immunodeficiency virus (HIV) infection has evolved from simple nucleoside reverse transcriptase inhibitor (NRTI) regimens to complex combination therapies based largely on evidence from clinical trials. However, the integration of novel ART into the clinical care of pediatric HIV infection has not been examined.
Objectives To describe changes in the treatment of pediatric HIV infection in the United States from 1987-2003, to assess concordance of initial regimens with US pediatric guidelines, and to identify predictors of the first regimen switch.
Design, Setting, and Participants The study population included 766 perinatally HIV-infected children in the Pediatric AIDS Clinical Trials Group 219C cohort born before January 1, 2004, who had not participated in an ART clinical trial at 219C enrollment or during follow-up.
Main Outcome Measures Proportion of children receiving specific ART regimens, proportion of children initiating ART according to pediatric guidelines, and time to first regimen switch (risk of switching).
Results Single and dual NRTI regimens were used most frequently through 1997. In 1998, 2 years after protease inhibitors were approved for adult HIV infection and at the time pediatric guidelines were issued, regimens of highly active antiretroviral therapy including a protease inhibitor became most frequently used. From 1998-2003, 22% of children initiated ART with a regimen not recommended by pediatric guidelines. In multivariate regression, the risk of switching decreased with age at ART initiation (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.94-0.99) and increased with year of initiation (HR, 1.28; 95% CI, 1.23-1.33). The risk of switching was higher in children who started with 1 NRTI (HR, 8.05; 95% CI, 5.80-11.18), 2 NRTIs (HR, 4.08; 95% CI, 3.08-5.40), or an unconventional regimen (HR, 6.23; 95% CI, 3.36-11.54) vs children who started with a protease inhibitor–containing regimen; and in children who initiated ART at CD4 T lymphocyte percentages less than 15 vs 15 or greater (HR, 2.90; 95% CI, 1.03-8.13).
Conclusions There was a short lag between the identification of novel ART and its adoption in the pediatric community. A variety of regimens were used, including some unorthodox therapies. Important predictors of first regimen switch were identified.
