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.

Congenital Anomalies and In Utero Antiretroviral Exposure in Human Immunodeficiency Virus–Exposed Uninfected Infants

“…19 This study includes two cohorts: Static and Dynamic. Between 2007 and 2009, the Static Cohort enrolled mothers/caregivers and their children under 12 years of age who had detailed information on ARV use during pregnancy and pregnancy outcomes.…”

Antiretroviral Drugs in Meconium: Detection for Different Gestational Periods of Exposure

“…Previously, these detection windows were studied by collecting other biological samples to assess drug exposure and timing of relapses. 7, 11, 16–18 Our novel analytical method allowed meconium quantification of ARVs from 4 diverse drug classes in a single sample, offering substantial improvements in assessing drug detection windows compared with previous studies and providing additional clinical relevance. ARV regimen changes during pregnancy offered a unique opportunity to investigate disposition of ARVs in meconium.…”

“…18 Mothers and infants enrolled in SMARTT’s Dynamic cohort between 22 weeks gestation and 1 week after birth. Institutional Review Boards at each site and the Harvard T.H.…”

Complications of cesarean deliveries among HIV-infected women in the United States

“…The great majority of these cesarean deliveries (over 90%) were elective, likely because of clinical guidelines recommending a prelabor cesarean delivery for HIV-infected women, unless their HIV viral load is less than 1000 copies/ml at 34 weeks gestation. Although it is possible that some women with viral load less than this cutoff may still undergo cesarean delivery, as most HIV-infected women in the United States are now on HAART regimens during pregnancy and achieve virologic suppression by their third trimester [41,42], the proportion of HIV-infected women undergoing cesarean delivery in the United States may decline. Indeed, in France the rate of elective cesarean delivery decreased since 2000 [31]; this has also been reported elsewhere in Europe [26]: The proportion of cesarean delivery in the French perinatal cohort was 52.9% in 2005 through 2010, which was twice the general French cesarean delivery rate [38].…”