Genetic variation in CCR2 and CXCL12 genes impacts on CD4 restoration in patients initiating cART with advanced immunesupression

PLoS One. 2019 Mar 28;14(3):e0214421. doi: 10.1371/journal.pone.0214421. eCollection 2019.

Abstract

Objective: We investigated the association of genetic polymorphisms in chemokine and chemokine receptor genes with poor immunological recovery in HIV patients starting combined antiretroviral therapy (cART) with low CD4 T-cell counts.

Methods: A case-control study was conducted in 412 HIV-infected patients starting cART with CD4 T-cell count <200 cells/μL and successful viral control for two years. CD4 count increase below 200 cells/μL after two years on cART was used to define INR (immunological non-responder) patients. Polymorphisms in CXCL12, CCL5 and CCR2 genes were genotyped using sequenom's MassARRAY platform.

Results: Thirty two percent (134/412) of patients were classified as INR. After adjusting by age, route of HIV infection, length of infection before cART and viral hepatitis coinfection, CCR2 rs1799864-AG genotype was significantly associated with INR status (OR [95% CI]: 1.80 [1.04-3.11]; p = 0.04), and CXCL12 rs1801157-TT genotype showed a trend (OR [95% CI]: 2.47 [0.96-6.35]; p = 0.06).

Conclusions: CCR2 rs1799864-AG or CXCL12 rs1801157-TT genotypes influence on the probability of poor CD4 recovery in the population of HIV patients starting cART with low CD4 counts. Genotyping of these polymorphisms could be used to estimate the risk of poor CD4 restoration, mainly in patients who are diagnosed late in the course of infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • Chemokine CXCL12 / genetics*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • HIV Infections / immunology
  • Humans
  • Immune Tolerance / drug effects
  • Immune Tolerance / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Receptors, CCR2 / genetics*
  • Retrospective Studies
  • Treatment Outcome
  • Virus Replication / drug effects

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12
  • Receptors, CCR2

Grants and funding

This work has been (partially) funded by the Spanish AIDS Research Network RD12/0017/0031, RD16/0025/0013, RD16CIII/0002/0002, and PI14CIII/00011 projects as part of the Health Research and Development Strategy, State Plan for Scientific and Technical Research and Innovation (2008-2011, 2013-2016) and co-financed by Institute of Health Carlos III, ISCIII-Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF). M Gutierrez-Rivas is funded by project RD16CIII/0002/0002. LM Medrano is supported by IISCIII, grant CD14/00002. F. Gutiérrez is supported by ISCIII, grants PI08/893, PI13/02256 and PI16/01740; FISABIO, grants UGP-14-197 and UGP-15-232, and RD16/0025/0038. N Rallón is a Miguel Servet investigator from the ISCIII (grant CP14/00198), Madrid, Spain. MA Navarrete-Muñoz is co-funded by RD16/0025/0013 project and Intramural Research Scholarship from IIS-FJD. M García is co-funded by CP14/00198 project and Intramural Research Scholarship from IIS-FJD. C Restrepo was funded by project RD12/0017/0031 and currently is funded by project RD16/0025/0013.