Longitudinal Analysis of Microbial Translocation Markers in Patients on Efavirenz and Lopinavir/ritonavir-based ART
Babilonia Barqasho*1, S Abdurahman1, P Nowak1,2, J Vesterbacka2, L-M Andersson3, J Svärd1, M Troseid4, M Gisslen3, and A Sönnerborg1,2
1Karolinska Inst, Stockholm, Sweden; 2Karolinska Univ Hosp, Stockholm, Sweden; 3Sahlgrenska Univ Hosp, Gothenburg, Sweden; and 4Oslo Univ Hosp, Norway
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.