Associations Between Plasma Immunomodulatory and Inflammatory Mediators With VACS Index Scores Among Older HIV-Infected Adults on Antiretroviral Therapy

Front Immunol. 2020 Jun 30:11:1321. doi: 10.3389/fimmu.2020.01321. eCollection 2020.


The prevalence of age-related comorbidities is increased in people living with HIV, even in those well-controlled on combination antiretroviral therapy (ART). Persistent immune activation and inflammation may play pivotal roles in the pathogenesis; however, the burden of morbidities in the older HIV infected population may be exacerbated and driven by distinct mechanisms. In a cross sectional study of 45 HIV-infected participants 60 years or older, we examined the relationships between 14 immunomodulatory and inflammatory factors and the Veterans Aging Cohort Study (VACS) Index, a metric of multimorbidity and mortality comprised of age, CD4 count, hemoglobin, Fibrosis-4 [FIB-4], and estimated glomerular filtration rate [eGFR], by linear regression analysis. All participants were virally suppressed (<50 HIV RNA copies/mL), on ART, and primarily Caucasian (86.7%), and male (91.1%). Plasma levels of monocyte/macrophage-associated (neopterin, IP-10, sCD163, sCD14, and MCP-1) and glycan-binding immunomodulatory factors (galectin (Gal)-1, Gal-3, and Gal-9) were assessed, as well as inflammatory biomarkers previously linked to the VACS Index (i.e., CRP, cystatin C, TNF-α, TNFRI, IL-6, and D-dimer) for comparison. In regression analysis, higher VACS index scores were associated with higher levels of neopterin, cystatin C, TNFRI, and Gal-9 (all p < 0.05), potentially driven by correlations found with individual VACS components, including age, CD4 count, FIB-4, and eGFR. Gal-9, cystatin C, and TNFRI directly correlated with the extent of multimorbidity. Multiple correlations among markers were observed, suggesting an interplay of overlapping, but distinct, pathways. Collectively, in addition to cystatin C and TNFRI, both galectin-9 and neopterin, independently emerged as novel fluid markers of the VACS Index and burden of comorbidity and may further guide in understanding pathogenic mechanisms of age-related disorders in older HIV-infected individuals on suppressive ART.

Keywords: HIV; aging; anti-retroviral therapy; inflammation; morbidity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aging / blood
  • Aging / immunology
  • Anti-Retroviral Agents / therapeutic use
  • Biomarkers / blood
  • Cohort Studies
  • Cystatin C / blood
  • Cytokines / blood
  • Female
  • Fibrin Fibrinogen Degradation Products / analysis
  • Galectins / blood
  • HIV / genetics
  • HIV Infections / blood*
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology
  • HIV Infections / virology
  • Humans
  • Inflammation Mediators / blood*
  • Male
  • Membrane Proteins / blood
  • Middle Aged
  • Neopterin / blood
  • RNA, Viral / blood
  • Veterans


  • Anti-Retroviral Agents
  • Biomarkers
  • CST3 protein, human
  • Cystatin C
  • Cytokines
  • Fibrin Fibrinogen Degradation Products
  • Galectins
  • Inflammation Mediators
  • Membrane Proteins
  • RNA, Viral
  • fibrin fragment D
  • Neopterin