Intestinal Barrier Dysfunction and Microbial Translocation in Human Immunodeficiency Virus-Infected Pregnant Women Are Associated with Preterm Birth

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 noninvasive 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 log 2 increase of each marker. Results In multivariable models, there was increased odds of PTB per unit increase of log 2 sCD14 (adjusted odds ratio [aOR], 2.45; 95% confidence interval [CI], 1.24-4.86), log 2 sCD163 (aOR, 3.87; 95% CI, 1.43-10.49), and log 2 I-FABP (aOR, 2.28; 95% CI, 1.18-4.41) but not log 2 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. Clinical Trials Registration NCT00061321.