Intestinal barrier dysfunction and microbial translocation in HIV-infected pregnant women is associated with preterm birth

Background:

Preterm birth (PTB) rates are high in HIV-infected populations, even when on treatment. Still, only a subset of all births in HIV-infected pregnant women result in PTB, suggesting risk factors other than HIV infection itself are also important. Inflammation is a known risk factor in uninfected populations but their 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 (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 (GA)). 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): 1.44-4.86), 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: 0.48-1.09).

Conclusions:

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