Decreased Activated CD4+ T Cell Repertoire Diversity After Antiretroviral Therapy in HIV-1/HCV Coinfection Correlates with CD4+ T Cell Recovery

Viral Immunol. 2021 Nov;34(9):622-631. doi: 10.1089/vim.2021.0027. Epub 2021 Oct 21.


Dysfunctional immune activation accumulates during chronic viral infection and contributes to disease pathogenesis. In HIV-1, immune activation is exacerbated by concurrent infection with hepatitis C virus (HCV), accelerating depletion of CD4+ T cells. HIV-1 suppression with antiretroviral therapy (ART) generally reconstitutes CD4+ T cell counts, while also reducing the proportion that is activated. Whether this immune reconstitution also reduces the complexity of the CD4+ T cell population is unknown. We sought to characterize the relationship between activated CD4+ T cell repertoire diversity and immune reconstitution following ART in HIV-1/HCV coinfection. We extracted T cell receptor (TCR) sequences from RNA sequencing data obtained from activated CD4+ T cells of HIV-1/HCV coinfected individuals before and after treatment with ART (clinical trial NCT01285050). There was notable heterogeneity in both the extent of CD4+ T cell reconstitution and in the change in activated CD4+ TCR repertoire diversity following ART. Decreases in activated CD4+ TCR repertoire diversity following ART were predictive of the degree of CD4+ T cell reconstitution. The association of decreased activated CD4+ TCR repertoire diversity and improved CD4+ T cell reconstitution may represent loss of nonspecifically activated TCR clonotypes, and possibly selective expansion of specifically activated CD4+ clones. These results provide insight into the dynamic relationship between activated CD4+ TCR diversity and CD4+ T cell recovery of HIV-1/HCV coinfected individuals after suppression of HIV-1 viremia.

Keywords: CD4-positive T lymphocytes; HIV; T cell; antigen; coinfection; hepatitis C; immune reconstitution; receptors.

Publication types

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

MeSH terms

  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes
  • Coinfection* / drug therapy
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • HIV-1*
  • Hepatitis C* / complications
  • Hepatitis C* / drug therapy
  • Humans