Frontiers in Cellular and Infection Microbiology (Mar 2022)

High Plasma sTNF-R1 Level Is Related to Loss of Natural HIV Control in Long-Term Elite Controllers

  • Daniel Sepúlveda-Crespo,
  • Norma Rallón,
  • Norma Rallón,
  • María José Muñoz-Gómez,
  • Oscar Brochado-Kith,
  • José Luis Jiménez,
  • José Luis Jiménez,
  • José Luis Jiménez,
  • María Ángeles Muñoz-Fernández,
  • María Ángeles Muñoz-Fernández,
  • María Ángeles Muñoz-Fernández,
  • María Ángeles Muñoz-Fernández,
  • José M. Benito,
  • José M. Benito,
  • Salvador Resino

DOI
https://doi.org/10.3389/fcimb.2022.858872
Journal volume & issue
Vol. 12

Abstract

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Human immunodeficiency virus-1 (HIV-1) elite controllers are heterogeneous due to different immunovirological features. We aimed to identify plasma biomarkers associated with loss of spontaneous HIV-1 control in long-term elite controllers (HIV-LTECs). We performed a retrospective study in 60 HIV-LTECs [36 true-LTECs and 24 LTECs losing control (LTECs-LC)]. We selected a plasma sample from true-LTECs (towards the middle of the follow-up period) and two samples from LTECs-LC (one far from the loss of control and another close to loss of control). Plasma biomarkers were evaluated using multiplex immunoassays. The partial least squares-discriminant analysis provided the variable importance in projection (VIP), and the adjusted Generalized Linear Model provided the adjusted arithmetic mean ratio (aAMR). At the moment of the first LTECs-LC samples, the only plasma biomarker with a VIP≥1.5 was sTNF-R1, which showed higher values in LTECs-LC than true-LTECs [aAMR=1.62 (95%CI=1.20-2.19); p=0.001]. After a median of 3.9 (IQR=4.5) years of follow-up from the first sample, we also had access to a second plasma sample from 10 LTECs-LC patients. At the moment of this second LTECs-LC sample, the only plasma biomarker with VIP≥1.5 was also sTNF-R1, which showed higher values in LTECs-LC than true-LTECs [aAMR=1.93 (95%CI=1.41-2.65); p<0.001]. The difference between the first and second samples of LTECs-LC was significant (Δx= 6.58 (95%=0.3; 12.88); p=0.040). In conclusion, high plasma values of sTNF-R1 appear to discriminate HIV-LTECs that lose the natural control of HIV-1, helping to define a specific phenotype that may be useful for the clinical management of these patients.

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