Intestinal barrier dysfunction and microbial translocation in human immunodeficiency virus–infected pregnant women are associated with preterm birth.

Shivakoti, R.; Gupte, N .; Kumar, N.P .; Kulkarni, V.; Balasubramanian, U.; Bhosale, R.; Sambrey, P .; Kinikar, A.; Bharadwaj, R .; Patil, S .; Inamdar, S .; Suryavanshi, N .; Babu, S.; Bollinger, R.; Gupta, A.

Clinical Infectious Diseases; 2018; 67(7): 1103-1109.

Background: Preterm birth (PTB) rates are high in human immunodeficiency virus (HIV)–infected populations, even when on treatment. Still, only a subset of all births in HIV-infected pregnant women result in PTB, suggesting that risk factors other than HIV infection itself are also important. Inflammation is a known risk factor in uninfected populations, but its role in HIV-infected population have not been studied; in addition, the immune pathways involved are not clear and non-invasive immune markers with predictive value are lacking. Our objective was to determine the association of select markers of inflammation with PTB in HIV-1–infected pregnant women.

Methods: Within a randomized trial of pregnant women receiving nevirapine (Six-Week Extended-Dose Nevirapine [SWEN] trial), we nested a case-control study (n = 107; 26 cases, 81 controls) to determine the association of maternal inflammation with PTB. Cases were defined as PTB (<37 weeks' gestational age). We assessed inflammation by measuring plasma levels of markers of general inflammation (C-reactive protein [CRP]), intestinal barrier dysfunction (intestinal fatty acid binding protein [I-FABP]), and microbial translocation/monocyte activation (soluble CD14 [sCD14] and CD163 [sCD163]). Multivariable logistic regression was used to determine the odds of PTB per log2 increase of each marker.

Results: In multivariable models, there was increased odds of PTB per unit increase of log2 sCD14 (adjusted odds ratio [aOR], 2.45; 95% confidence interval [CI], 1.24–4.86), log2 sCD163 (aOR, 3.87; 95% CI, 1.43–10.49), and log2 I-FABP (aOR, 2.28; 95% CI, 1.18–4.41) but not log2 CRP (aOR, 0.72; 95% CI, .48–1.09).

Conclusions: Our results show that select immune markers can identify women at higher risk for PTB in HIV-1–infected populations and suggest that modulating gut barrier integrity and microbial translocation may affect PTB.

Keywords: Preterm birth; HIV; Microbial translocation; Inflammation; Intestinal integrity

Clinical Trials Registration: NCT00061321.

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