Observational study of effects of HIV acquisition and antiretroviral treatment on biomarkers of systemic immune activation.
Ewelina KosmiderJackson WallnerAna GervassiRachel Bender IgnacioDelia Pinto-SantiniGermán Gustavo GornalusseUrvashi PandeyFlorian HladikPaul T EdlefsenJavier R LamaAnn C DuerrLisa M FrenkelPublished in: PloS one (2024)
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.
Keyphrases
- antiretroviral therapy
- hiv infected
- hiv positive
- hiv testing
- men who have sex with men
- human immunodeficiency virus
- hiv infected patients
- hiv aids
- cardiovascular disease
- hepatitis c virus
- binding protein
- rheumatoid arthritis
- drug delivery
- oxidative stress
- south africa
- dendritic cells
- skeletal muscle
- high throughput
- toll like receptor
- climate change
- polycystic ovary syndrome
- risk assessment
- lps induced
- endothelial cells
- sensitive detection
- single molecule
- replacement therapy
- single cell