title: A trigger-based design for evaluating the safety of in utero antiretroviral exposure in uninfected children of human immunodeficiency virus-infected mothers.
abstract: The Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites between 2007 and 2011 that was designed to evaluate the safety of in utero antiretroviral drug exposure in children not infected with human immunodeficiency virus who were born to mothers who were infected. This ongoing study uses a "trigger-based" design; that is, initial assessments are conducted on all children, and only those meeting certain thresholds or "triggers" undergo more intensive evaluations to determine whether they have had an adverse event (AE). The authors present the estimated rates of AEs for each domain of interest in the Surveillance Monitoring of ART Toxicities Study. They also evaluated the efficiency of this trigger-based design for estimating AE rates and for testing associations between in utero exposures to antiretroviral drugs and AEs. The authors demonstrate that estimated AE rates from the trigger-based design are unbiased after correction for the sensitivity of the trigger for identifying AEs. Even without correcting for bias based on trigger sensitivity, the trigger approach is generally more efficient for estimating AE rates than is evaluating a random sample of the same size. Minor losses in efficiency when comparing AE rates between persons exposed and unexposed in utero to particular antiretroviral drugs or drug classes were observed under most scenarios.
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, USA. paige@sdac.harvard.edu
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
authors.forename: George R
authors.initials: GR
authors.lastname: Seage
authors.forename: Russell B
authors.initials: RB
authors.lastname: Van Dyke
authors.forename: George K
authors.initials: GK
authors.lastname: Siberry
authors.forename: Raymond
authors.initials: R
authors.lastname: Griner
authors.forename: Katherine
authors.initials: K
authors.lastname: Tassiopoulos
authors.forename: Cenk
authors.initials: C
authors.lastname: Yildirim
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Read
authors.forename: Yanling
authors.initials: Y
authors.lastname: Huo
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: Denise L
authors.initials: DL
authors.lastname: Jacobson
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Mofenson
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rich
mesh_terms: D000465:Algorithms; D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D018811:Maternal Exposure; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D049188:Prenatal Injuries / Q000139:chemically induced*; D011446:Prospective Studies; D012107:Research Design
chemical_list: D044966:Anti-Retroviral Agents