Effects of co-trimoxazole on microbial translocation in HIV-1 infected patients initiating antiretroviral therapy

Jan Vesterbacka1, Babilonia Barqasho2, Amanda Häggblom2, Anders Sönnerborg1,2, Piotr Nowak1,2
Affiliates: 1Department of Medicine, Unit of Infectious Diseases and 2Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden

Background
Microbial translocation (MT) contributes to immune activation during HIV-1 infection, and persists after initiation of antiretroviral therapy (ART).

Methods
Plasma samples were obtained from HIV-1 infected patients initiating ART with (n= 13) or without (n= 13) co-trimoxazole (TMP-SMX) prophylaxis. MT markers lipopolysaccharide (LPS), LPS-binding protein (LBP), soluble CD14 (sCD14), and intestinal fatty acid binding protein (I-FABP) were assessed by Limulus Amebocyte Lysate Assay and ELISA at baseline (BL), follow up at one month, and after one year.

Results
BL levels of LBP were elevated in patients starting ART with TMP-SMX prophylaxis (median 36669 vs. 4320 ng/ml; p= 0.001), and correlated to CD4+ T-cell count (ρ= -0.65; p= 0.005). A significant reduction between BL and one year follow up was seen in patients receiving ART and TMP-SMX only (median 36669 vs. 11105 ng/ml; p=0.003). This decline was confirmed in a generalized linear mixed-effects model adjusting for relevant co-variables at BL. Levels of LPS at BL were lower in patients starting ART with ongoing TMP-SMX prophylaxis (median 221 vs. 303; p=0.002) and did not change until one year. BL levels of sCD14 tended to be lower in patients starting ART only, and declined in both groups until one year. Levels of I-FABP were stable between BL and one year follow-up.

Conclusions
LBP kinetics was independently associated with usage of co-trimoxazole prophylaxis. ART with or without TMP-SMX prophylaxis reduced sCD14 levels, but other markers of MT were not significantly improved during one year follow-up. Concomitant use of TMP-SMX may be associated with less MT compared to ART alone, possibly due to its impact on the gut microbiota.