Gerhard Theron1, Grace Montepiedra2, Lisa Aaron2, Katie McCarthy3, Nahida Chakhtoura4, Patrick Jean-Philippe5, Bonnie Zimmer6, Amy James Loftis7, Tsungai Chipato8, Teacler Nematadzira9, Mandisa Nyati10, Carolyne Onyango-Makumbi11, Gaerolwe Masheto12, James Ngocho13, Fuanglada Tongprasert14,15, Sandesh Patil16, Dominique Lespinasse17, Adriana Weinberg18, Amita Gupta19. 1. Department of Obstetrics and Gynaecology, Stellenbosch University, Cape Town, South Africa. 2. Center for Biostatistics in AIDS Research, Harvard TH Chan School of Public Health, Boston, Massachusetts, USA. 3. FHI 360, Durham, North Carolina, USA. 4. Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA. 5. National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA. 6. Frontier Science Foundation, Amherst, New York, USA. 7. University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 8. Department of Obstetrics and Gynaecology, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe. 9. University of Zimbabwe College of Health Sciences-Clinical Trials Research Centre, Harare, Zimbabwe. 10. Perinatal Human Immunodeficiency Virus (HIV) Research Unit, University of the Witwatersrand, Johannesburg, South Africa. 11. Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda. 12. Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. 13. Department of Epidemiology and Applied Biostatistics, Kilimanjaro Christian Medical University College, Moshi, Tanzania. 14. Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai, Thailand. 15. Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand. 16. Byramjee Jeejeebhoy Government Medical College, Johns Hopkins University Clinical Research Site, Pune, India. 17. Les Centres GHESKIO, Port-au-Prince, Haiti. 18. Departments of Pediatrics, Medicine and Pathology, University of Colorado Denver Anschutz Medical Center, Aurora, Colorado, USA. 19. Center for Clinical Global Health Education, Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Abstract
BACKGROUND:International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1078, a randomized noninferiority study designed to compare the safety of starting isoniazid preventive therapy (IPT) in women living with human immunodeficiency virus (HIV) either during pregnancy or after delivery, showed that IPT during pregnancy increased the risk of composite adverse pregnancy outcomes, but not individual outcomes. Many known factors are associated with adverse pregnancy outcomes: these factors' associations and effect modifications with IPT and pregnancy outcomes were examined. METHODS:Pregnant women living with HIV from 8 countries with tuberculosis incidences >60/100 000 were randomly assigned to initiate 28 weeks of IPT either during pregnancy or at 12 weeks after delivery. Using univariable and multivariable logistic regression and adjusting for factors associated with pregnancy outcomes, composite and individual adverse pregnancy outcome measures were analyzed. RESULTS: This secondary analysis included 925 mother-infant pairs. All mothers were receiving antiretrovirals. The adjusted odds of fetal demise, preterm delivery (PTD), low birth weight (LBW), or a congenital anomaly (composite outcome 1) were 1.63 times higher among women on immediate compared to deferred IPT (95% confidence interval [CI], 1.15-2.31). The odds of fetal demise, PTD, LBW, or neonatal death within 28 days (composite outcome 2) were 1.62 times higher among women on immediate IPT (95% CI, 1.14-2.30). The odds of early neonatal death within 7 days, fetal demise, PTD, or LBW (composite outcome 3) were 1.74 times higher among women on immediate IPT (95% CI, 1.22-2.49). CONCLUSIONS: We confirmed higher risks of adverse pregnancy outcomes associated with the initiation of IPT during pregnancy, after adjusting for known risk factors for adverse pregnancy outcomes.
RCT Entities:
BACKGROUND: International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1078, a randomized noninferiority study designed to compare the safety of starting isoniazid preventive therapy (IPT) in women living with human immunodeficiency virus (HIV) either during pregnancy or after delivery, showed that IPT during pregnancy increased the risk of composite adverse pregnancy outcomes, but not individual outcomes. Many known factors are associated with adverse pregnancy outcomes: these factors' associations and effect modifications with IPT and pregnancy outcomes were examined. METHODS: Pregnant women living with HIV from 8 countries with tuberculosis incidences >60/100 000 were randomly assigned to initiate 28 weeks of IPT either during pregnancy or at 12 weeks after delivery. Using univariable and multivariable logistic regression and adjusting for factors associated with pregnancy outcomes, composite and individual adverse pregnancy outcome measures were analyzed. RESULTS: This secondary analysis included 925 mother-infant pairs. All mothers were receiving antiretrovirals. The adjusted odds of fetal demise, preterm delivery (PTD), low birth weight (LBW), or a congenital anomaly (composite outcome 1) were 1.63 times higher among women on immediate compared to deferred IPT (95% confidence interval [CI], 1.15-2.31). The odds of fetal demise, PTD, LBW, or neonatal death within 28 days (composite outcome 2) were 1.62 times higher among women on immediate IPT (95% CI, 1.14-2.30). The odds of early neonatal death within 7 days, fetal demise, PTD, or LBW (composite outcome 3) were 1.74 times higher among women on immediate IPT (95% CI, 1.22-2.49). CONCLUSIONS: We confirmed higher risks of adverse pregnancy outcomes associated with the initiation of IPT during pregnancy, after adjusting for known risk factors for adverse pregnancy outcomes.
Authors: Samantha R Kaplan; Jaclyn N Escudero; Jerphason Mecha; Barbra A Richardson; Elizabeth Maleche-Obimbo; Daniel Matemo; John Kinuthia; Grace C John-Stewart; Sylvia M LaCourse Journal: J Acquir Immune Defic Syndr Date: 2022-01-01 Impact factor: 3.771
Authors: Katelyn A Pastick; Enock Kagimu; Joanna Dobbin; Kenneth Ssebambulidde; Jane Gakuru; Jack Milln; Betty Nakabuye; David B Meya; David R Boulware; Fiona V Cresswell; Nathan C Bahr Journal: Open Forum Infect Dis Date: 2022-10-06 Impact factor: 4.423