Persistently biased T-cell receptor repertoires in HIV-1-infected combination antiretroviral therapy-treated patients despite sustained suppression of viral replication

Antonello Giovannetti, Marina Pierdominici, Marco Marziali, Francesca Mazzetta, Elisabetta Caprini, Giandomenico Russo, Roberto Bugarini, Maria Livia Bernardi, Ivano Mezzaroma, Fernando Aiuti

Research output: Contribution to journalArticle

Abstract

In most HIV-1-infected patients, highly active antiretroviral therapy (HAART) reduces plasma viral load to + T-cell number and function. However, it is still unclear whether alterations of T-cell receptor (TCR) β-chain variable region (BV) repertoire, tightly related to disease progression, can be fully recovered by long-term treatment with HAART. This study analyzed the evolution of both T-cell subset composition and TCRBV perturbations in chronically HIV-1-infected patients with moderate immunodeficiency during 36 months of HAART. Despite persistently suppressed HIV replication, the rate of CD4+ T-cell repopulation, after an initial burst, progressively declined throughout the study period, resulting in a mean CD4+ T-cell count at the end of follow-up that was still significantly lower in HIV patients than in HIV-seronegative controls. This was seen in association with an incomplete restitution of both CD4 and CD8 TCRBV repertoire disruptions and was also demonstrated by the appearance of new TCRBV oligoclonal expansions occurring during HAART. In conclusion, these data indicate that 3 years of fully suppressive HAART may be not adequate to normalize CD4 counts and TCRBV repertoires in patients starting HAART with moderately advanced disease.

Original languageEnglish
Pages (from-to)140-154
Number of pages15
JournalJournal of Acquired Immune Deficiency Syndromes
Volume34
Issue number2
DOIs
Publication statusPublished - Oct 1 2003

Keywords

  • HAART
  • HIV-1
  • T lymphocytes
  • T-cell receptor

ASJC Scopus subject areas

  • Immunology
  • Virology

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