Background
Elite controllers (EC) are an exceptional group of people living with HIV (PLWH) able to control HIV replication without antiretroviral therapy and have been proposed as a model of functional HIV cure. However, significant evidence suggests that despite viral control, EC subjects may have altered levels of activation and systemic inflammation. We have characterized the systemic inflammation profile in EC compared to non-controllers PLWH with ART-mediated control of viral replication.
Methods
30 participants were included: 10 EC, 10 non-controllers PLWH on ART (ART), and 10 uninfected controls (UC) as reference. Plasmatic levels of markers of inflammation (sTNFR1, sTNF2, hsCRP), endothelial activation (sICAM1, sVCAM1), monocyte activation (sCD14), intestinal barrier permeability (FABP2) and coagulopathy (d-Dimer, PAI-1), were assessed using enzyme-linked immunosorbent assay (ELISA). Inter-group differences were tested by non-parametric tests (Kruskall-Wallis; Mann-Whitney) and a discriminant analysis was employed to ascertain the markers involved in discriminating between pairs of study
Results
EC and ART groups were matched for CD4 counts, years since diagnosis, route of acquisition and gender. The profile of alterations (taking UC group as reference) of the markers analyzed was different in EC and ART. ART group presented increased levels of sVCAM1 (714[564-890] vs. 474[332-741] ng/mL in ART and UC; p=0.086), whereas EC group presented increased levels of sCD14 (1210[990-1944] vs. 965[574-1140] ng/mL in EC and UC; p=0.054). Moreover, sVCAM was increased in ART group compared to EC group (714[564-890] vs. 560[377-636] ng/mL; p=0.041). The discriminant models were able to separate between EC and UC groups (proportion of individuals correctly classified by the model was 70% and 80% for EC and UC respectively; sCD14 was the only variable in the model); and between EC and ART groups (proportion of individuals correctly classified by the model was 70% and 70% for EC and ART respectively; sVCAM was the only variable in the model)
Conclusions
Our results show the existence of a chronic inflammatory status in PLWH in spite of controlled viral replication. Interestingly the profile of inflammation differs according to the mechanism of HIV control and points to monocyte activation as a main driver in PLWH EC. Further studies are warranted to test the effect of differential biomarkers levels on the profile of morbidities observed in PLWH with different mechanisms of viral suppression
Table or Figure
