PD-1 Expression in HIV-Specific CD8+ T cells before Antiretroviral Therapy Is Associated with HIV Persistence

Yanina Ghiglione, César Trifone, Jimena Salido, Ajantha Rhodes, María Julia Ruiz, María Laura Polo, Horacio Salomón, Natalia Laufer, Omar Sued, Sharon R. Lewin, Gabriela Turk

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Background:The persistence of latently infected T cells remains the principal barrier to HIV cure. Understanding how the early immune responses shape persistence of HIV on antiretroviral therapy (ART) will be fundamental for potential eradication. Here, we aimed to determine the relationship between CD8+ T-cell function and phenotype before therapy and HIV persistence on ART.Methods:Blood samples from 29 individuals enrolled during primary HIV infection (at baseline and every 3 months up to 2 years post-ART initiation) were obtained. HIV-specific T-cell function and expression of the activation markers were evaluated before ART by flow cytometry. Cell-associated HIV DNA and unspliced (US)-RNA were quantified in purified CD4+ T cells by real-time polymerase chain reaction. Data were analyzed using nonparametric statistics.Results:Elevated immune activation, dominance of monofunctional CD8+ T cells, and skewed distribution of memory profile were observed before ART. After ART initiation, HIV DNA and US-RNA levels rapidly diminished, reaching a plateau by 30 weeks after ART. The proportion of baseline HIV-specific effector memory and terminal effector CD8+ T cells directly correlated with HIV DNA levels at 1 year after ART. A strong positive correlation was observed between the proportion of bulk and HIV-specific PD-1High CD8+ T cells measured before ART and HIV DNA at 1 year after ART.Conclusions:A higher proportion of terminally differentiated CD8+ T cells and increased PD1 expression were associated with HIV persistence on ART after treatment of primary infection. Thus, the quality of the early CD8+ T-cell immune response may serve as a predictor of HIV persistence on ART.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalJournal of Acquired Immune Deficiency Syndromes
Volume80
Issue number1
DOIs
StatePublished - 1 Jan 2019
Externally publishedYes

Keywords

  • CD8 T cells
  • HIV
  • PD-1
  • immune response
  • viral reservoir

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