School of Public Health

Daniel R. Drozd

Effect of Antiretroviral Therapy on Damage-Associated Molecular Patterns (DAMPs). Lipopolysacharide (LPS) and Immune Reconstitution in HIV-Infected Individuals

BACKGROUND

Even with successful antiretroviral therapy (ART), HIV infection is still accompanied by ongoing chronic immune activation and inflammation that may impact ART-mediated immune reconstitution. The mechanisms of this immune activation are not completely defined. Damage-associated molecular patterns (DAMPs) are endogenous innate immune activators that have not been well studied in HIV-infected persons.

METHODS

We conducted a quasi-experimental pre-post observational study of two DAMPs (HMGB1 and S100A9) and a marker of microbial translocation (LPS) in samples collected from research participants before and at least 2 years after initiation of continuously suppressive ART. Differences in mean biomarker levels were assessed using paired t-tests. Correlation between biomarker levels were assessed using Pearson correlation coefficients for normal data and Spearman's rho for non-normal data. Multivariate linear regression was used to assess association between biomarker values and clinical outcomes after suppressive ART.

RESULTS

Mean HMGB1 levels increased between pre- and post-ART samples (1.95 ng/mL vs. 3.02 ng/mL, p=0.01) and the proportion of individuals with detectable S100A9 increased significantly (p=0.01). We detected no change in mean LPS levels with effective ART (p=0.85). Neither LPS, HMGB1, nor S100A9 was associated with baseline CD4 or viral load or degree of CD4 reconstitution with effective ART-mediated viral suppression.

CONCLUSIONS

DAMPs do not appear to be significantly associated with CD4 count, viral load, or degree of CD4 reconstitution after virologic suppression. Increased HMGB1 levels after suppressive ART may be a non-specific marker of inflammation and hence subject to confounding by other conditions.

URI: http://hdl.handle.net/1773/33160