Persistence of monocyte activation under treatment in people followed since acute HIV-1 infection relative to participants at high or low risk of HIV infection

EBioMedicine. 2020 Dec:62:103129. doi: 10.1016/j.ebiom.2020.103129. Epub 2020 Nov 26.

Abstract

Background: Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We compared the inflammatory profiles of HIV-infected participants under long-term antiretroviral therapy (ART) with those of two HIV-uninfected groups with contrasting health behaviours.

Methods: We studied 150 HIV-infected participants (42 women, 108 men) under long-term ART (median, 6 years) followed in the ANRS PRIMO cohort since acute/early HIV-1 infection (AHI) diagnosis. Sex and age-matched controls were sampled from i) the ANRS IPERGAY pre-exposure prophylaxis trial among men at high risk for HIV infection and with high frequencies of non-HIV factors of inflammation ii) the ANRS COHVAC cohort of volunteers in vaccine trials with a low-risk profile for HIV infection. We measured the plasma levels of ten inflammatory markers.

Findings: After adjusting for smoking, alcohol use and body mass index, both HIV-infected men and women had higher levels of sCD14, sCD163, sTNFRII and I-FABP than their high-risk IPERGAY and low-risk COHVAC counterparts. Hierarchical clustering showed a subset of 15 PRIMO participants to have an inflammatory profile similar to that of most HIV-negative participants. These participants already had favourable markers at AHI diagnosis.

Interpretation: Long-term ART, even when initiated at a low level of immunodeficiency, fails to normalize monocyte/macrophage activation and gut epithelial dysfunction. Persistent inflammation under treatment may be related to an increased inflammatory profile since AHI.

Funding: ANRS and Paris-Saclay University.

Keywords: HIV infection; Immune activation; Inflammation; Long-term ART.

MeSH terms

  • Acute Disease
  • Adult
  • Antiretroviral Therapy, Highly Active
  • Biomarkers
  • Cytokines / metabolism
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • HIV Infections / virology*
  • HIV-1*
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Inflammation Mediators
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Risk Factors

Substances

  • Biomarkers
  • Cytokines
  • Inflammation Mediators