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Randomized Controlled Trial
. 2024 Jul 1;38(8):1111-1119.
doi: 10.1097/QAD.0000000000003877. Epub 2024 Mar 19.

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

Rupak Shivakoti  1 , Mark J Giganti  2 , Michael M Lederman  3 , Rachel Ketchum  2 , Sean Brummel  2 , Daniela Moisi  3 , Sufia Dadabhai  4 , Dhayendre Moodley  5   6 , Avy Violari  7 , Lameck Chinula  8 , Maxensia Owor  9 , Amita Gupta  10 , Judith S Currier  11 , Taha E Taha  4 , Mary Glenn Fowler  12 ; PROMISE study team
Affiliations
Randomized Controlled Trial

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

Rupak Shivakoti et al. AIDS. .

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 multicountry 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 with zidovudine alone, the difference in biomarker concentration between week 0 and week 4 was significantly higher ( P < 0.05) for both protease inhibitor-based regimens. However, the estimated proportion of the ART effect on increased PTD mediated by persistently high biomarker levels was 5% or less for all biomarkers.

Conclusion: Persistently high IL-6 during pregnancy was associated with PTD. Although protease inhibitor-based ART was associated with increases in inflammation, factors other than inflammation likely explain the increased PTD in ART-based regimens compared with zidovudine alone.

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Conflict of interest statement

The authors have no relevant conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Forest plot for treatment effect on change in immune marker concentrations.
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