Grace Montepiedra1, Soyeon Kim2, Adriana Weinberg3, Gerhard Theron4, Timothy R Sterling5, Sylvia M LaCourse6, Sarah Bradford7, Nahida Chakhtoura8, Patrick Jean-Philippe8, Scott Evans9, Amita Gupta10. 1. Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA. 2. Frontier Science Foundation, Boston, Massachusetts, USA. 3. University of Colorado, Denver, Colorado, USA. 4. Stellenbosch University, Cape Town, South Africa. 5. Vanderbilt University Medical Center, Nashville, Tennessee, USA. 6. University of Washington, Seattle, Washington, USA. 7. FHI 360, Durham, North Carolina, USA. 8. National Institutes of Health, Bethesda, Maryland, USA. 9. The George Washington University, Washington, DC, USA. 10. Johns Hopkins University, Baltimore, Maryland, USA.
Abstract
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. Clinical Trials Registration. NCT01494038 (IMPAACT P1078).
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. Clinical Trials Registration. NCT01494038 (IMPAACT P1078).
Authors: E Rogozinska; M I D'Amico; K S Khan; J G Cecatti; H Teede; S Yeo; C A Vinter; G Rayanagoudar; R Barakat; M Perales; J M Dodd; R Devlieger; A Bogaerts; M N M van Poppel; L Haakstad; G X Shen; A Shub; R Luoto; T I Kinnunen; S Phelan; L Poston; T T Scudeller; N El Beltagy; S N Stafne; S Tonstad; N R W Geiker; A E Ruifrok; B W Mol; A Coomarasamy; S Thangaratinam Journal: BJOG Date: 2016-01 Impact factor: 6.531
Authors: Scott R Evans; Mikael Knutsson; Pierre Amarenco; Gregory W Albers; Philip M Bath; Hans Denison; Per Ladenvall; Jenny Jonasson; J Donald Easton; Kazuo Minematsu; Carlos A Molina; Yongjun Wang; Ks Lawrence Wong; S Claiborne Johnston Journal: Clin Trials Date: 2020-07-15 Impact factor: 2.486
Authors: Jeanne S Sheffield; David Siegel; Mark Mirochnick; R Phillips Heine; Christine Nguyen; Kimberly L Bergman; Rada M Savic; Jill Long; Kelly E Dooley; Mirjana Nesin Journal: Clin Infect Dis Date: 2014-12-15 Impact factor: 9.079