Kinetics of Microbial Translocation Markers in Patients on Efavirenz or Lopinavir/r Based Antiretroviral Therapy

Abstract

ObjectivesWe investigated whether there are differences in the effects on microbial translocation (MT) and enterocyte damage by different antiretroviral therapy (ART) regimens after 1.5 years and whether antibiotic use has impact on MT. In a randomized clinical trial (NCT01445223) on first line ART, patients started either lopinavir/r (LPV/r) (n = 34) or efavirenz (EFV) containing ART (n = 37). Lipopolysaccharide (LPS), sCD14, anti-flagellin antibodies and intestinal fatty acid binding protein (I-FABP) levels were determined in plasma at baseline (BL) and week 72 (w72).ResultsThe 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. 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 (Δ = −0.47 µg/ml; p = 0.015).ConclusionsMarkers of MT and enterocyte damage are elevated in untreated HIV-1 infected patients. Long-term ART reduces the levels, except for I-FABP which role as a marker of MT is 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 RegistrationClinicalTrials.gov NCT01445223

Sex differences in soluble markers vary before and after the initiation of antiretroviral therapy in chronically HIV-infected individuals

“…Other studies have determined the effect of cART on microbial translocation markers such as I-FABP and sCD14, and similarly found I-FABP levels increased in individuals taking efavirenz (EFV) [38]. In our study, there was no correlation between I-FABP levels and treatment with EFV, and there was no bias of EFV usage in females over males.…”

Immune Activation Is Associated With Increased Gut Microbial Translocation in Treatment-Naive, HIV-Infected Children in a Resource-Limited Setting

“…A strong inverse correlation of sCD14 with CD4 + T cells and a direct correlation of sCD14 with VL have been previously reported. 5,46 We found an inverse correlation of sCD14 with CD4% but did not find any correlation with VL (data not shown). T-cell IA was correlated with monocyte activation at baseline, suggesting that there is generalized IA.…”

Predictors of virologic response in persons who start antiretroviral therapy during recent HIV infection

“…Although previous associations have been described between viral load and sCD14 levels [24], to our knowledge this is the first study to link baseline sCD14 with virologic response during ART. Although limited by the number of participants providing gut biopsies, we also observed that starting ART in early HIV infection did not improve recovery of CD4 + T-cell proportions in GALT, despite all participants starting ART within 30 days of EDI.…”

“…We also observed a significant and continued loss of central memory CD4 + T cells over time in the GALT despite ART. This could possibly be due to ongoing HIV replication in GALT, as previously described [26] or due to cell-mediated death of latently infected CD4 + T cells, especially in the presence of significantly increasing proportions of effector CD8 + T cells [24–27,32,33]. …”