Kinetics of microbial translocation markers in patients on efavirenz or lopinavir/r based antiretroviral therapy

• Published in: PloS one Vol. 8; no. 1; p. e55038
• Main Authors: Vesterbacka, Jan, Nowak, Piotr, Barqasho, Babilonia, Abdurahman, Samir, Nyström, Jessica, Nilsson, Staffan, Funaoka, Hiroyuki, Kanda, Tatsuo, Andersson, Lars-Magnus, Gisslèn, Magnus, Sönnerborg, Anders
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2013; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Anti-Bacterial Agents - pharmacology; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antibiotics; Antibodies; Antibodies, Bacterial - immunology; Antibodies, Bacterial - metabolism; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Apoptosis; Bacteria - drug effects; Bacteria - immunology; Bacteria - metabolism; Benzoxazines - pharmacology; Benzoxazines - therapeutic use; Biology; Biomarkers - metabolism; Bowel disease; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Clinical Medicine; Damage; Deoxyribonucleic acid; DNA; Drug Combinations; Drug therapy; Efavirenz; Farmakologi och toxikologi; Fatty acid-binding protein; Fatty Acid-Binding Proteins - metabolism; Fatty acids; Female; Flagellin; Flagellin - immunology; Highly active antiretroviral therapy; HIV; HIV-1 - drug effects; HIV-1 - physiology; Hospitals; Human immunodeficiency virus; Humans; Infections; Infectious diseases; Infektionsmedicin; Intestine; Kinetics; Klinisk medicin; Laboratories; Lipopolysaccharide Receptors - chemistry; Lipopolysaccharide Receptors - metabolism; Lipopolysaccharides; Lipopolysaccharides - metabolism; Lopinavir; Lopinavir - pharmacology; Lopinavir - therapeutic use; Male; Markers; Medicin; Medicin och hälsovetenskap; Medicine; Medicinska och farmaceutiska grundvetenskaper; Microorganisms; Middle Aged; Mitogens; Movement - drug effects; Patients; Plasma; Protein binding; Proteins; Solubility; Therapy; Time Factors; Translocation; Viral Load - drug effects; Young Adult; Sweden
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0055038

We 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). 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. 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). 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 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. ClinicalTrials.gov NCT01445223.