Tuberculosis Preventive Treatment for Pregnant People With Human Immunodeficiency Virus in South Africa: A Modeling Analysis of Clinical Benefits and Risks

Linzy V Rosen; Acadia M Thielking; Caitlin M Dugdale; Grace Montepiedra; Emma Kalk; Soyeon Kim; Sylvia M LaCourse; Jyoti S Mathad; Kenneth A Freedberg; C Robert Horsburgh; A David Paltiel; Robin Wood; Andrea L Ciaranello; Krishna P Reddy

doi:10.1093/cid/ciae508

Tuberculosis Preventive Treatment for Pregnant People With Human Immunodeficiency Virus in South Africa: A Modeling Analysis of Clinical Benefits and Risks

Clin Infect Dis. 2024 Nov 15:ciae508. doi: 10.1093/cid/ciae508. Online ahead of print.

Authors

Linzy V Rosen¹, Acadia M Thielking¹, Caitlin M Dugdale^{1

2

3}, Grace Montepiedra⁴, Emma Kalk⁵, Soyeon Kim⁶, Sylvia M LaCourse^{7

8

9}, Jyoti S Mathad^{10

11}, Kenneth A Freedberg^{1

2

3

12

13}, C Robert Horsburgh^{14

15}, A David Paltiel¹⁶, Robin Wood^{17

18}, Andrea L Ciaranello^{1

2

3}, Krishna P Reddy^{1

2

19}

Affiliations

¹ Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
² Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
³ Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁴ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
⁵ Centre for Infectious Disease Epidemiology and Research, School of Public Health, Faculty of Health Sciences, University of Cape Town, Cape Town, Western Cape, South Africa.
⁶ Frontier Science Foundation, Brookline, Massachusetts, USA.
⁷ Department of Global Health, University of Washington, Seattle, Washington, USA.
⁸ Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA.
⁹ Department of Epidemiology, University of Washington, Seattle, Washington, USA.
¹⁰ Department of Medicine, Center for Global Health, Weill Cornell Medicine/New York Presbyterian Hospital, New York, New York, USA.
¹¹ Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, New York, USA.
¹² Division of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹³ Department of Health Policy and Management, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
¹⁴ Boston University School of Public Health, Boston, Massachusetts, USA.
¹⁵ Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
¹⁶ Public Health Modeling Unit, Yale School of Public Health, New Haven, Connecticut, USA.
¹⁷ Desmond Tutu Health Foundation, Mowbray, Cape Town, Western Cape, South Africa.
¹⁸ Department of Medicine, University of Cape Town, Cape Town, Western Cape, South Africa.
¹⁹ Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.

PMID: 39544107
DOI: 10.1093/cid/ciae508

Abstract

Background: Although prior studies of tuberculosis-preventive treatment (TPT) for pregnant people with human immunodeficiency virus (PPWH) report conflicting adverse pregnancy outcome (APO) risks, international guidelines recommend TPT for PPWH.

Methods: We used a microsimulation model to evaluate 5 TPT strategies among PPWH receiving antiretroviral therapy in South Africa: No TPT; 6 months of isoniazid (6H) or 3 months of isoniazid-rifapentine (3HP) during pregnancy (Immediate 6H or Immediate 3HP) or post partum (Deferred 6H or Deferred 3HP). The primary outcomes were maternal, fetal/infant, and combined deaths from causes potentially influenced by TPT (maternal tuberculosis, maternal hepatotoxicity, stillbirth, low birth weight [LBW], and infant tuberculosis). Tuberculosis during pregnancy confers 250% and 81% higher modeled risks of stillbirth and LBW, respectively. In lower-risk or higher-risk scenarios, immediate TPT confers 38% lower or 92% higher risks of stillbirth and 16% lower or 35% higher risks of LBW.

Results: Immediate TPT would minimize deaths among PPWH. When TPT confers higher stillbirth and LBW risks, immediate TPT would produce the most combined maternal and fetal/infant deaths, even with low maternal CD4 cell count and high tuberculosis incidence. If immediate TPT yields a <4% or <20% increase in stillbirth or LBW, immediate TPT would produce fewer combined deaths than deferred TPT (sensitivity analysis range, <2%-22% and <11%-120%, respectively).

Conclusions: If APO risks are below identifiable thresholds, TPT during pregnancy could decrease combined maternal and fetal/infant deaths. Given uncertainty around isoniazid's risks, and the low threshold at which APO risks could outweigh benefits from tuberculosis deaths averted, studies of newer TPT regimens among PPWH are warranted to inform guidelines.

Keywords: HIV; adverse pregnancy outcome; pregnancy; tuberculosis; tuberculosis preventive treatment.

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Abstract

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