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Longitudinal analysis of microbial translocation markers in patients on efavirenz or lopinavir/r based antiretroviral therapy
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Reported by Jules Levin
CROI 2012 March 5-8 Seattle WA
B. Barqasho1, S. Abdurahman2, P. Nowak1,2, J. Vesterbacka2, L-M Andersson3, J. Svard2, M. Trosseid4, M. Gisslen3, A. Sonnerborg1,2
1Department of Laboratory Medicine, Division of Clinical Microbiology and, 2Department of Medicine, Division of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, 3Department of Infectious Diseases, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, 4Department of Infectious Diseases, Medical Division, Oslo University Hospital, Norway
Conclusions
Effective ART treatment decreases markers of MT (sCD14, anti-flagellin Ab and Total IgG), while I-FABP levels are elevated after 1,5 years of ART.
Our study indicates that the level of MT might differ in subjects on dissimilar ART despite of comparable virological and immunological outcome.
Background: Persistent immune activation and systemic inflammation is associated with HIV-1 infection even in the era of successful ART. We investigated markers of microbial translocation/immune activation (sCD14, anti-flagellin antibodies, intestinal fatty acid binding protein (I-FABP)) at baseline (BL) and after 72 weeks on ART, and compared the outcome between the lopinavir/ritonavir (LPV/r) and efavirenz (EFV) containing treatment arms.
Methods: In a retrospective sub-study of a randomized clinical trial on the first-line ART (NorthHIV trial), we enrolled 71 patients who started either LPV/r (n = 34) or EFV (n = 37) containing ART. Plasma levels of sCD14, anti-flagellin antibodies, and I-FABP were determined by ELISA. Non-parametric statistics were applied.
Results: Plasma sCD14 levels were overall reduced at week 72 as compared to BL (3.13 μg/mL [IQR 2.7 to 3.8] vs 2.85 μg/mL [IQR 2.4 to 3.4]; p = 0.005). A significant negative correlation (r = 0.42, p = 0.0003) between CD4+ T cells and sCD14 was observed at BL, and maintained at week 72. I-FABP levels were increased at week 72 in the whole group (median 2.26 ng/mL [IQR 1.4 to 3.6] at BL vs 3.13 ng/mL [IQR 1.8 to 4.9] at week 72; p = <0.0001). This increase was present in EFV-treated subjects (2.32 [IQR 1.5 to 3.8] at BL vs 4.29 [IQR 2.4 to 5.9] at week 72; p = <0.0001). On the contrary in LPV/r-treated patients, there was no difference between BL and week 72 I-FABP levels (2.19 vs 2.56). Levels of anti-flagellin antibodies were reduced by median of 28% in LPV/r arm (p = 0.001), contrary to EFV-treated patients, which had a median increase of 7.5% in their anti-flagellin antibody levels (p = 0.06). The same trend was observed when the ratio between anti-flagellin antibodies and total immunoglobulin G was calculated.
Conclusions: Subjects in LPV/r-based therapy had lower levels of immune activation (I-FABP and anti-flagellin specific antibodies) at 72 weeks post-ART. Our study indicates that levels of immune activation could differ in subjects on dissimilar ART despite of comparable virological and immunological outcome.
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