Endothelial Glycocalyx Integrity in Treatment-Naïve People Living with HIV before and One Year after Antiretroviral Treatment Initiation

Viruses. 2023 Jul 5;15(7):1505. doi: 10.3390/v15071505.

Abstract

Endothelial glycocalyx (EG) derangement has been associated with cardiovascular disease (CVD). Studies on EG integrity among people living with HIV (PLWH), are lacking. We conducted a prospective cohort study among treatment-naïve PLWH who received emtricitabine/tenofovir alafenamide, combined with either an integrase strand transfer inhibitor (INSTI, dolutegravir, raltegravir or elvitegravir/cobicistat), or a protease inhibitor (PI, darunavir/cobicistat). We assessed EG at baseline, 24 (±4) and 48 (±4) weeks, by measuring the perfused boundary region (PBR, inversely proportional to EG thickness), in sublingual microvessels. In total, 66 consecutive PLWH (60 (90.9%) males) with a median age (interquartile range, IQR) of 37 (12) years, were enrolled. In total, 40(60.6%) received INSTI-based regimens. The mean (standard deviation) PBR decreased significantly from 2.17 (0.29) μm at baseline to 2.04 (0.26) μm (p = 0.019), and then to 1.93 (0.3) μm (p < 0.0001) at 24 (±4) and 48 (±4) weeks, respectively. PBR did not differ among treatment groups. PLWH on INSTIs had a significant PBR reduction at 48 (±4) weeks. Smokers and PLWH with low levels of viremia experienced the greatest PBR reduction. This study is the first to report the benefit of antiretroviral treatment on EG improvement in treatment-naïve PLWH and depicts a potential bedside biomarker and therapeutic target for CVD in PLWH.

Keywords: HIV; antiretroviral treatment; atherosclerosis; biomarkers; endothelial glycocalyx; integrase inhibitor; permeable boundary region; protease inhibitor.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents* / therapeutic use
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Endothelium* / drug effects
  • Endothelium* / pathology
  • Female
  • Glycocalyx* / drug effects
  • Glycocalyx* / pathology
  • HIV Infections* / drug therapy
  • HIV Infections* / pathology
  • Humans
  • Male
  • Middle Aged
  • Smoking
  • Viral Load

Substances

  • Anti-HIV Agents

Grants and funding

For P.C.F.: This research is co-financed by Greece and the European Union (European Social Fund—ESF) through the Operational Program «Human Resources Development, Education and Lifelong Learning» in the context of the project “Strengthening Human Resources Research Potential via Doctorate Research—2nd Cycle” (MIS-5000432), implemented by the State Scholarships Foundation (ΙΚΥ) (Grant number: 2018-050-0502-14473). This funding does not support a publication fee. None of the other authors received any funding for this project.