Effect of Antiretroviral Therapy on Damage-Associated Molecular Patterns (DAMPs). Lipopolysacharide (LPS) and Immune Reconstitution in HIV-Infected Individuals
Year: 2015
Type: dissertation
Study design: Observational Study
Abstract: 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.Damageassociated 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.
Author: Daniel R. Drozd
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: University of Washington
OpenAlex ID: W2597763413