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- Title
Observational study of effects of HIV acquisition and antiretroviral treatment on biomarkers of systemic immune activation.
- Authors
Kosmider, Ewelina; Wallner, Jackson; Gervassi, Ana; Bender Ignacio, Rachel A.; Pinto-Santini, Delia; Gornalusse, German; Pandey, Urvashi; Hladik, Florian; Edlefsen, Paul T.; Lama, Javier R.; Duerr, Ann C.; Frenkel, Lisa M.
- Abstract
To assess whether biomarkers of systemic inflammation are associated with HIV acquisition or with the timing of ART initiation ("immediate", at diagnosis, versus "deferred", at 24 weeks post-diagnosis) in men-who-have-sex-with-men (MSM) and transgender women, we conducted a retrospective study comparing inflammatory biomarkers in participants' specimens collected before infection and after ≥2 years of effective ART. We measured biomarkers in four longitudinally collected plasma, including two specimens collected from each participant before and two after HIV acquisition and confirmed ART-suppression. Biomarkers were quantified by enzyme-linked immuno-assay or Meso Scale Discovery. When evaluating systematic variation in these markers over time, we found that multiple biomarkers consistently varied across participants' two pre-infection or two post-ART-suppression specimens. Additionally, we compared changes in biomarkers after vs before HIV acquisition. Across 47 participants, the levels of C-reactive protein (CRP), monocyte chemo-attractant protein-1, tumor necrosis factor-α and interferon gamma-induced protein-10 significantly increased while leptin and lipopolysaccharide binding protein (LBP) significantly decreased following HIV infection. Randomization to deferred-ART initiation was associated with greater increases in CRP and no decrease in LBP. Acquisition of HIV appeared to induce systemic inflammation, with elevation of biomarkers previously associated with infections and cardiovascular disease. Initiation of ART during the early weeks of infection tempered the increase in pro-inflammatory biomarkers compared to delaying ART for ~24 weeks after HIV diagnosis. These findings provide insight into potential mediators by which immediate-ART initiation improves health outcomes, perhaps because immediate-ART limits the size of the HIV reservoir or limits immune dysregulation that in turn trigger systemic inflammation. Author summary: A comparison of biomarkers of systemic inflammation were compared across 47 participants' specimens, two collected before infection and two after ≥2 years of effective ART. The levels of C-reactive protein, monocyte chemo-attractant protein-1, tumor necrosis factor-α and interferon gamma-induced protein-10 significantly increased while leptin and lipopolysaccharide binding protein significantly decreased following HIV infection.
- Subjects
ANTIRETROVIRAL agents; BIOMARKERS; HIV; HIV infections; CARRIER proteins; RALTEGRAVIR; EFAVIRENZ; C-reactive protein; LEPTIN
- Publication
PLoS ONE, 2024, Vol 19, Issue 7, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0288895