title: Effects of Co-Trimoxazole on Microbial Translocation in HIV-1-Infected Patients Initiating Antiretroviral Therapy.
abstract: Microbial translocation (MT) contributes to immune activation during HIV-1 infection, and persists after initiation of antiretroviral therapy (ART). We investigated whether levels of MT markers are influenced by the use of co-trimoxazole (TMP-SMX) in HIV-1 patients. Plasma samples were obtained from HIV-1-infected patients initiating ART with (n=13) or without (n=13) TMP-SMX prophylaxis. Markers of MT [lipopolysaccharide-binding protein (LBP), lipopolysaccharide (LPS), soluble CD14 (sCD14), and intestinal fatty acid binding protein (I-FABP)] were assessed at baseline (BL), at 1 month, and at 1 year by the Limulus Amebocyte Lysate Assay or ELISA. BL levels of LBP were elevated in both categories of patients; they were highest in patients starting ART and TMP-SMX (median, μg/ml: 36.7 vs. 4.3, respectively, p=0.001) and correlated inversely with CD4(+) T cell counts (ρ=-0.65; p=0.005). Patients receiving ART and TMP-SMX had a significant reduction in LBP between BL and 1 year (median, μg/ml: 36.7 vs. 11.1; p=0.003). In contrast, levels of LPS at BL were lower in patients starting ART and TMP-SMX compared to those without TMP-SMX (median, pg/ml: 221 vs. 303 respectively; p=0.002) and did not change at 1 year. The increased BL levels of sCD14 had declined in both groups at 1 year. No difference in I-FABP levels was found between BL and 1 year. Concomitant use of ART and TMP-SMX reduces microbial translocation markers LBP and sCD14, probably due to its impact on the gut microbiota. Effective ART for 1 year does not restore gut-blood barrier dysfunction.
authors.affiliation: 1 Department of Medicine, Unit of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital Huddinge , Stockholm, Sweden .
authors.forename: Jan
authors.initials: J
authors.lastname: Vesterbacka
authors.affiliation: 2 Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital Huddinge , Stockholm, Sweden .
authors.forename: Babilonia
authors.initials: B
authors.lastname: Barqasho
authors.affiliation: 1 Department of Medicine, Unit of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital Huddinge , Stockholm, Sweden .|3 Department of Infectious Diseases, County Council of Gävleborg , Gävle, Sweden .
authors.forename: Amanda
authors.initials: A
authors.lastname: Häggblom
authors.affiliation: 1 Department of Medicine, Unit of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital Huddinge , Stockholm, Sweden .|2 Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital Huddinge , Stockholm, Sweden .
authors.forename: Piotr
authors.initials: P
authors.lastname: Nowak
mesh_terms: D000209:Acute-Phase Proteins; D000328:Adult; D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis / Q000379:methods*; D018988:Bacterial Translocation / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage*; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D000900:Anti-Bacterial Agents; D044966:Anti-Retroviral Agents; D015415:Biomarkers; D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D000099231:Lipopolysaccharide-Binding Protein