{
  "abstract": "Background Despite virologically suppressive ART, residual inflammation persists in people with HIV (PWH), thus driving higher risk of serious non-AIDS events (SNAEs) and mortality. Circulating HIV proteins have been detected in some suppressed PWH, as an expression of the persistence of the translation-competent reservoir. We therefore seek to investigate whether peripheral inflammation is associated with p24 production in this population.Methods PWH on suppressive ART and age/sex-matched healthy controls without HIV were enrolled. Ultra-low level serum p24 was cross-sectionally (baseline) and longitudinally (6 and 12 months) quantified by Simoa following immune complexes acid dissociation. In addition, the following were cross-sectionally measured at baseline: plasma biomarkers of inflammaging (Luminex/ELISA), CD38+CD8+ T-cells (flow cytometry), cell-associated (CA) total/unintegrated/integrated HIV DNA and RNA (qPCR). VACS Index 2.0 was computed to estimate physiologic frailty and mortality risk. In vitro experiments tested whether p24 modulates IP-10 secretion by PBMCs.Results 120 PWH and 20 controls were recruited. PWH (83.3% males) had a median age of 54 (IQR 47–59) years, and were on ART for 10 (6–19) years, with a current CD4 T-cell count of 725 (504–908) cells/μL. PWH exhibited a distinct inflammaging profile characterised by higher IP-10, TNF-α, IL-17A, IL-8, sCD14, sCD163, TIMP-1, and GDF-15 than controls. Several biomarkers were associated with the VACS Index 2.0 in univariable analyses, but only IP-10 and GDF-15 remained independently associated in multivariable modelling. By setting the p24 positivity cut-off at 0.025 pg/mL based on the mean+3SD of controls, soluble p24 was detectable in 25/120 (20.8%) PWH at baseline (median: 0.0516 pg/mL; range: 0.0264–0.8280 pg/mL) ( figure 1A). p24 detectability was associated with male sex yet not with immunological parameters, ART duration/regimen, or CA HIV DNA and RNA. Among inflammaging biomarkers, p24 was associated exclusively with higher plasma IP-10, both as categorical and continuous variable, even after adjustment for sex, age, CD4 T-cell count, and ART duration (figure 1B–C). Longitudinal analyses in a subset of 30 PWH revealed dynamic p24 patterns, with persistently p24-positive PWH [8/30 (26.7%)] exhibiting the highest baseline IP-10 levels (figure 1D–E). In vitro, p24 alone did not induce IP-10 secretion by PBMCs, but in the presence of IFN-γ+TNF-α, it produced a modest yet significant increase, supporting a context-dependent proinflammatory effect (figure 1F).Conclusions These findings demonstrate that a subset (~21%) of virologically suppressed PWH produce detectable levels of soluble p24, and that this residual HIV protein expression is selectively associated with an IP-10–dominant inflammatory profile. Given the positive association between IP-10 and VACS Index 2.0, these data suggest that p24-driven inflammation may contribute to SNAEs and mortality in virologically suppressed PWH.Abstract OC40 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "M Augello"
    },
    {
      "affiliations": [
        "Clinic of Neurology, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "A Mingione"
    },
    {
      "affiliations": [
        "Department of Biomolecular Sciences, University of Urbino ‘Carlo Bo’, Urbino, Italy"
      ],
      "name": "C Orlandi"
    },
    {
      "affiliations": [
        "Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "R Rovito"
    },
    {
      "affiliations": [
        "Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "V Bono"
    },
    {
      "affiliations": [
        "Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "V Sala"
    },
    {
      "affiliations": [
        "Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "C Tincati"
    },
    {
      "affiliations": [
        "Clinic of Neurology, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "F Martinelli Boneschi"
    },
    {
      "affiliations": [
        "Department of Biomolecular Sciences, University of Urbino ‘Carlo Bo’, Urbino, Italy"
      ],
      "name": "A Casabianca"
    },
    {
      "affiliations": [
        "Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "G Marchetti"
    }
  ],
  "title": "OC40 Ultra-low level soluble p24 production identifies an IP-10-dominant inflammatory signature linked to physiologic frailty and mortality risk in virologically suppressed people with HIV",
  "uid": "6d25dcff-e3fc-5c3f-8ab1-da99a48dbcb3"
}