Systemic inflammation in pregnant women with HIV: relationship with HIV treatment regimen and preterm delivery

Rupak Shivakoti; Mark J Giganti; Michael M Lederman; Rachel Ketchum; Sean Brummel; Daniela Moisi; Sufia Dadabhai; Dhayendre Moodley; Avy Violari; Lameck Chinula; Maxensia Owor; Amita Gupta; Judith S Currier; Taha E Taha; Mary Glenn Fowler; PROMISE study team

doi:10.1097/QAD.0000000000003877

Systemic inflammation in pregnant women with HIV: relationship with HIV treatment regimen and preterm delivery

AIDS. 2024 Feb 26. doi: 10.1097/QAD.0000000000003877. Online ahead of print.

Authors

Affiliations

¹ Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA.
² Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
³ Department of Medicine, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
⁴ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁵ Department of Obstetrics and Gynaecology, School of Clinical Medicine, University of KwaZulu Natal, Durban, South Africa; Centre for the Program of AIDS Research in South Africa (CAPRISA), Durban, South Africa.
⁶ Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁷ Department of Obstetrics & Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁸ Makerere University-John Hopkins University Research Collaboration (MUJHU CARE LTD) CRS, Kampala, Uganda.
⁹ Division of Infectious Diseases, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁰ Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
¹¹ Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 38411599
DOI: 10.1097/QAD.0000000000003877

Abstract

Objective: : HIV treatment regimen during pregnancy was associated with preterm delivery (PTD) in the PROMISE 1077 BF trial. Systemic inflammation among pregnant women with HIV could help explain differences in PTD by treatment regimen. We assessed associations between inflammation, treatment regimen, and PTD.

Design/methods: : A nested 1:1 case-control study (N = 362) was conducted within a multi-country randomized trial comparing three HIV regimens in pregnant women: zidovudine alone, or combination antiretroviral therapy (ART) with lopinavir/ritonavir and either zidovudine or tenofovir. Cases were women with PTD (<37 weeks of gestational age). The following inflammatory biomarkers were measured in plasma samples using immunoassays: soluble CD14 (sCD14) and sCD163, intestinal fatty acid-binding protein, interleukin (IL)-6, interferon γ, and tumor necrosis factor α. We fit regression models to assess associations between second trimester biomarkers (measured before ART initiation at 13-23 weeks of gestational age and 4 weeks later), treatment regimen, and PTD. We also assessed whether inflammation was a mediator in the relationship between ART regimen and PTD.

Results: : Persistently high interleukin-6 was associated with increased PTD. Compared to zidovudine alone, the difference in biomarker concentration between week 0 and week 4 was significantly higher (p < 0.05) for both PI-based regimens. However, the estimated proportion of the ART effect on increased PTD mediated by persistently high biomarker levels was ≤5% for all biomarkers.

Conclusions: : Persistently high IL-6 during pregnancy was associated with PTD. While PI-based ART was associated with increases in inflammation, factors other than inflammation likely explain the increased PTD in ART-based regimens compared to zidovudine alone.