Antiretroviral therapy reduces but does not normalize immune and vascular inflammatory markers in adults with chronic HIV infection in Kenya

AIDS. 2021 Jan 1;35(1):45-51. doi: 10.1097/QAD.0000000000002729.

Abstract

Introduction: Markers of monocyte/macrophage activation and vascular inflammation are associated with HIV-related cardiovascular diseases (CVD) and mortality. We compared these markers among African people living with HIV (PLWH) and HIV-negative adults, and examined risk factors associated with elevated biomarkers (>75th percentile) in PLWH on antiretroviral therapy (ART).

Design: Cross-sectional study.

Methods: We measured serum concentrations of a gut integrity biomarker (intestinal-fatty acid binding protein), monocyte/macrophage activation biomarkers (soluble CD14 and CD163), and vascular inflammation biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular adhesion molecule 1 (sVCAM-1)]. We assessed the relationship of these inflammatory parameters with HIV, using logistic regression adjusting for traditional CVD risk factors.

Results: Among the 541 participants, median age was 43 years and half were female. Among 275 PLWH, median CD4 T-cell count and duration of ART use was 509 cells/μl and 8 years, respectively. PLWH had significantly higher prevalence of elevated inflammatory biomarkers compared with HIV-negative individuals even after adjustment for traditional CVD risk factors. Compared with individuals without HIV, the prevalence of elevated biomarkers was highest among persons with detectable viral load and CD4 T-cell counts 200 cells/μl or less. In a subanalysis among PLWH, nadir CD4 T-cell count 200 cells/μl or less was associated with elevated soluble CD14 (sCD14); dyslipidemia with elevated sCD14, sICAM-1, and sVCAM-1; and overweight/obesity with reduced sCD14. Longer ART exposure (>4 years) was associated with reduced sVCAM-1 and sICAM-1.

Conclusion: HIV and not traditional CVD risk factors is a primary contributor of monocyte/macrophage activation and inflammation despite ART. Anti-inflammatory therapies in addition to ART may be necessary to reduce these immune dysregulations and improve health outcomes of African PLWH.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Biomarkers / metabolism
  • Cross-Sectional Studies
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • HIV Infections* / immunology
  • Humans
  • Kenya / epidemiology
  • Lipopolysaccharide Receptors
  • Viral Load

Substances

  • Anti-Retroviral Agents
  • Biomarkers
  • Lipopolysaccharide Receptors