Persistent enterocyte damage despite decreased microbial translocation in patients on effective antiretroviral therapy

Abstract

Intestinal fatty acid binding protein (I‐FABP) was proposed as a plasma marker of enterocyte turnover that could be applied to estimate the level of gut damage in HIV‐1 infected patients. We investigated the kinetics of I‐FABP in patients starting antiretroviral therapy (ART) in a clinical cohort (CC) (n=32), and in a clinical trial (RCT), where patients were randomized to lopinavir/r (LPV/r) or efavirenz (EFV)‐based therapy (n=71). I‐FABP was analyzed at baseline (BL) and after 48 and 72 weeks of ART, respectively. Additionally we estimated levels of LPS and sCD14 in both cohorts. At baseline, we found elevated plasma levels of I‐FABP, LPS, and sCD14 in patients with HIV‐1 infection as compared to controls. During ART I‐FABP levels increased from BL to week 48 (1.66 ng/ml [IQR 1.29–2.88] vs. 2.56 ng/ml [IQR 1.29–5.26]; p=0.02) in CC group. Similar pattern was seen in the RCT group at week 72 as compared to BL (2.26 ng/ml [IQR 1.4–3.6] vs 3.13 ng/ml [IQR 1.8–4.9]; p<0.0001). Levels of sCD14 decreased at the end of study period in both groups. The levels of LPS decreased in RCT cohort but not in CC cohort. Interestingly, we found that the I‐FABP levels increased in both cohorts despite 48–72 weeks of efficient ART. A subgroup analysis of the RCT cohort revealed that the I‐FABP increase occurred in the patients treated with EFV (2.32 ng/ml [IQR 1.5–3.8] vs. 4.29 ng/ml [IQR 2.4–5.9]; p<0.0001), but not in those with LPV/r. This finding was not confirmed in the CC group. The possibility of immune reconstitution in the gut as a cause of the increasing I‐FABP levels seems to be less likely, as CD4 T‐cell recovery tended to be lower in efavirenz‐treated patients. In RCT cohort, the established MT markers lipopolysaccharide (LPS) and sCD14 were both reduced after 72 weeks (data not shown), supporting a reduced MT. Most likely the systemic I‐FABP levels in patients on ART do not reflect only MT itself. Further studies should address this issue.