Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2012 May 1;175(9):950-61.
doi: 10.1093/aje/kwr401. Epub 2012 Apr 6.

A trigger-based design for evaluating the safety of in utero antiretroviral exposure in uninfected children of human immunodeficiency virus-infected mothers

Paige L Williams  1 , George R Seage 3rd, Russell B Van Dyke, George K Siberry, Raymond Griner, Katherine Tassiopoulos, Cenk Yildirim, Jennifer S Read, Yanling Huo, Rohan Hazra, Denise L Jacobson, Lynne M Mofenson, Kenneth Rich; Pediatric HIV/AIDS Cohort Study
Collaborators, Affiliations
Multicenter Study

A trigger-based design for evaluating the safety of in utero antiretroviral exposure in uninfected children of human immunodeficiency virus-infected mothers

Paige L Williams et al. Am J Epidemiol. .

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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Hypothetical example of a study with 1,000 subjects and a trigger rate of 10% for a particular adverse event (AE). Shaded boxes show unobserved outcomes.
Figure 2.
Figure 2.
Efficiency of a trigger-based study design versus random subset design for estimating the rate of adverse events (AEs) (A) and for estimating log odds ratio (OR) (B), based on sample sizes of 1,000 and a true adverse event rate of 0.04. Shown is the ratio of the mean squared error (MSE) of the random subset design to the trigger-based design, with values above 1indicating greater efficiency of the trigger-based design.
Figure 3.
Figure 3.
Power for detecting an exposure effect based on a trigger-based design versus a full cohort design and random subset design as a function of sensitivity of the trigger assuming a background adverse event (AE) rate in the unexposed of 4%, n = 1,500, and relative risk = 2.
See this image and copyright information in PMC

References

    1. Townsend CL, Cortina-Borja M, Peckham CS, et al. Low rates of mother-to-child transmission of HIV following effective pregnancy interventions in the United Kingdom and Ireland, 2000–2006. AIDS. 2008;22(8):973–981. - PubMed
    1. Cooper ER, Charurat M, Mofenson L, et al. Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission. Women and Infants’ Transmission Study Group. J Acquir Immune Defic Syndr. 2002;29(5):484–494. - PubMed
    1. Suksomboon N, Poolsup N, Ket-aim S. Systematic review of the efficacy of antiretroviral therapies for reducing the risk of mother-to-child transmission of HIV infection. J Clin Pharm Ther. 2007;32(3):293–311. - PubMed
    1. Public Health Service recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. MMWR Morb Mortal Wkly Rep. 1998;47(RR-2):1–38. - PubMed
    1. European Collaborative Study. Exposure to antiretroviral therapy in utero or early life: the health of uninfected children born to HIV-infected women. J Acquir Immune Defic Syndr. 2003;32(4):380–387. - PubMed

Publication types

Substances