The levels of anti-flagellin antibodies had decreased at w72 (0.35 vs 0.31 [OD]; p 0.0004), although significantly only in the LPV/r arm. Results The levels of LPS and sCD14 were reduced from BL to w72 (157.5 pg/ml vs. 140.0 pg/ml, p?=?0.0003; 3.13 ug/ml vs. A-366 2.85 ug/ml, p?=?0.005, respectively). The levels of anti-flagellin antibodies had decreased at w72 (0.35 vs 0.31 [OD]; p 0.0004), although significantly only in the LPV/r arm. I-FABP levels increased at w72 (2.26 ng/ml vs 3.13 ng/ml; p 0.0001), although significantly in EFV treated patients only. Patients given antibiotics at BL had lower sCD14 levels at w72 as revealed by ANCOVA compared to those who did not receive A-366 (?=??0.47 g/ml; p?=?0.015). Conclusions Markers of MT and enterocyte damage are elevated in untreated HIV-1 infected patients. Long-term ART reduces the levels, except for I-FABP which A-366 role as a marker of MT is usually questionable in ART-experienced patients. Why the enterocyte damage seems to persist remains to be established. Also antibiotic usage may influence the kinetics of the markers of MT. Trial Registration ClinicalTrials.gov “type”:”clinical-trial”,”attrs”:”text”:”NCT01445223″,”term_id”:”NCT01445223″NCT01445223 Introduction A sustained control of the human immunodeficiency virus type 1 (HIV-1) replication is obtained by antiretroviral therapy (ART) in the majority of patients, reducing plasma HIV-1 load to undetectable levels. However, HIV-1 persists in reservoirs like latently infected CD4+ T cells [1], [2] and in body compartments that have restricted permission for antiretroviral drugs. It is hypothesized that these reservoirs are refilled by the low grade viral replication seen in patients on suppressive ART who otherwise have undetectable viremia by routine assays [3], [4]. Translocation of bacterial products across a Rabbit Polyclonal to UBXD5 damaged gut-blood barrier has been proposed to be one important mechanism for the persistence of a chronic immune activation which is found also in well-treated patients [5], [6]. There is growing evidence that this immune activation may contribute to the low-grade viremia and e.g. cardiovascular and CNS complications [7], [8], [9]. Several markers are used to assess microbial translocation (MT) in patients with HIV or inflammatory bowel disease [10], such as microbial products [lipopolysaccharide (LPS), plasma bacterial 16SrDNA, anti-flagellin antibodies] [11], markers of the systemic response to bacterial products (sCD14, LPS-binding protein), and of enterocyte damage [intestinal fatty acid binding protein (I-FABP)] [12], [13]. During successful ART, MT and systemic immune activation are usually reduced, but not normalized, suggesting that this damage of the gut-blood barrier is only partly restored [5]. The reasons why this improvement varies between patients are not known. The origin of low-level viremia in patients on suppressive ART has been disputed. Residual virus replication from anatomical compartments like the gut could be one of the explanations. Firstly, levels of HIV-1 DNA and RNA were substantially elevated in the gut compared with peripheral blood in patients on ART with 40 HIV-1 RNA copies/ml, indicating that the gut may serve as a potential source of viremia during suppressive ART [14]. Additionally, in a set of patients on long-term ART, levels of HIV DNA in sigmoid colon were positively correlated to plasma LPS levels [15], suggesting a connection between residual viremia and MT. In a cross-sectional study of patients with persistently undetectable HIV-1 RNA, a higher proportion of participants treated with nevirapine and efavirenz achieved 2.5 HIV-1 RNA copies/ml compared to lopinavir/r based ART [16]. Given the link between MT and low-level viremia, we assumed that choice of ART could differently affect kinetics of MT markers. In the present study, we analyzed the levels of LPS, sCD14, I-FABP, and anti-flagellin antibodies, at baseline (BL) and after 72 weeks (w72) of ART in a controlled randomized clinical trial in which the patients received either lopinavir/r +2 nucleoside analogues (NRTI) or efavirenz +2 NRTI. Additionally, we studied if ongoing antibiotics treatment had an impact around the explored parameters. Methods Subjects During 2004C2007, 239 HIV-1.