TY - JOUR
T1 - Using a Composite Maternal-Infant Outcome Measure in Tuberculosis-Prevention Studies among Pregnant Women
AU - Montepiedra, Grace
AU - Kim, Soyeon
AU - Weinberg, Adriana
AU - Theron, Gerhard
AU - Sterling, Timothy R.
AU - Lacourse, Sylvia M.
AU - Bradford, Sarah
AU - Chakhtoura, Nahida
AU - Jean-Philippe, Patrick
AU - Evans, Scott
AU - Gupta, Amita
N1 - Funding Information:
Potential conflicts of interest. S. E. reports personal fees from Takeda/Millennium, Pfizer, Roche, Novartis, Achaogen, Huntington’s Study Group, ACTTION, Genentech, Amgen, GSK, American Statistical Association, FDA, Osaka University, Nationa Cerebral and Cardiovascular Center of Japan, the National Institutes of Health (NIH), Society for Clinical Trials, Statistical Communications in Infectious Diseases (DeGruyter), AstraZeneca, Teva, Austrian Breast and Colorectal Cancer Study Group/Breast International Group and the Alliance Foundation Trials, Zeiss, Dexcom, American Society for Microbiology, Taylor and Francis, Claret Medical, Vir, Arrevus, Five Prime, Shire, Alexion, Gilead, Spark, Clinical Trials Transformation Initiative, Nuvelution, Tracon, Deming Conference, Antimicrobial Resistance and Stewardship Conference, World Antimicrobial Congress, WAVE, Advantagene, Braeburn, Cardinal Health, Lipocine, Microbiotix, and Stryker, and grants from National Institute of Allergy and Infectious Diseases (NIAID)/NIH (grant for Statistical and Data Management Center for the Antibacterial Resistance Leadership Group), outside the submitted work. A. W. reports grants from Merck, GSK, and NIH, outside of the submitted work. G.M., A.G. and T.R.S. report grants from the NIH during the conduct of the study, outside the submitted work. A. G. and T. R. S. report grants from the NIH during the conduct of the study, outside the submitted work. S. B. reports grants from the NIH during the conduct of the study. All other authors report no potential conflicts.
Funding Information:
Financial support. This work was supported by the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH), all components of the National Institutes of Health (NIH), under award numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC), and UM1AI106716 (IMPAACT LC), and by NICHD contract number HHSN275201800001I. S. M. L. is supported by the NIAID (NIH/NIAID K23AI120793). A. G. is supported by NIH/NIAID grant UM1AI069465.
Publisher Copyright:
© 2020 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2021/8/1
Y1 - 2021/8/1
N2 - Background: Tuberculosis (TB-)-preventive therapy (TPT) among pregnant women reduces risk of TB in mothers and infants, but timing of initiation should consider potential adverse effects. We propose an analytical approach to evaluate the risk-benefit of interventions. Methods: A novel outcome measure that prioritizes maternal and infant events was developed with a 2-stage Delphi survey, where a panel of stakeholders assigned scores from 0 (best) to 100 (worst) based on perceived desirability. Using data from TB APPRISE, a trial among pregnant women living with human immunodeficiency virus (WLWH) that randomized the timing of initiation of isoniazid, antepartum versus postpartum, was evaluated. Results: The composite outcome scoring/ranking system categorized mother-infant paired outcomes into 8 groups assigned identical median scores by stakeholders. Maternal/infant TB and nonsevere adverse pregnancy outcomes were assigned similar scores. Mean (SD) composite outcome scores were 43.7 (33.0) and 41.2 (33.7) in the antepartum and postpartum TPT initiation arms, respectively. However, a modifying effect of baseline antiretroviral regimen was detected (P = .049). When women received nevirapine, composite scores were higher (worse outcomes) in the antepartum versus postpartum arms (adjusted difference, 14.3; 95% confidence interval [CI], 2.4-26.2; P = .02), whereas when women received efavirenz there was no difference by timing of TPT (adjusted difference,. 62; 95% CI,-3.2-6.2; P = .53). Conclusions: For TPT, when used by otherwise healthy persons, preventing adverse events is paramount from the perspective of stakeholders. Among pregnant WLWH in high-TB-burden regions, it is important to consider the antepartum antiretroviral regimen taken when deciding when to initiate TPT.
AB - Background: Tuberculosis (TB-)-preventive therapy (TPT) among pregnant women reduces risk of TB in mothers and infants, but timing of initiation should consider potential adverse effects. We propose an analytical approach to evaluate the risk-benefit of interventions. Methods: A novel outcome measure that prioritizes maternal and infant events was developed with a 2-stage Delphi survey, where a panel of stakeholders assigned scores from 0 (best) to 100 (worst) based on perceived desirability. Using data from TB APPRISE, a trial among pregnant women living with human immunodeficiency virus (WLWH) that randomized the timing of initiation of isoniazid, antepartum versus postpartum, was evaluated. Results: The composite outcome scoring/ranking system categorized mother-infant paired outcomes into 8 groups assigned identical median scores by stakeholders. Maternal/infant TB and nonsevere adverse pregnancy outcomes were assigned similar scores. Mean (SD) composite outcome scores were 43.7 (33.0) and 41.2 (33.7) in the antepartum and postpartum TPT initiation arms, respectively. However, a modifying effect of baseline antiretroviral regimen was detected (P = .049). When women received nevirapine, composite scores were higher (worse outcomes) in the antepartum versus postpartum arms (adjusted difference, 14.3; 95% confidence interval [CI], 2.4-26.2; P = .02), whereas when women received efavirenz there was no difference by timing of TPT (adjusted difference,. 62; 95% CI,-3.2-6.2; P = .53). Conclusions: For TPT, when used by otherwise healthy persons, preventing adverse events is paramount from the perspective of stakeholders. Among pregnant WLWH in high-TB-burden regions, it is important to consider the antepartum antiretroviral regimen taken when deciding when to initiate TPT.
KW - Pregnancy
KW - Prioritized composite outcomes
KW - Risk-benefit analysis
KW - Tuberculosis
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U2 - 10.1093/cid/ciaa1674
DO - 10.1093/cid/ciaa1674
M3 - Article
C2 - 33146706
AN - SCOPUS:85113714632
SN - 1058-4838
VL - 73
SP - E587-E593
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 3
ER -