title: Persistently biased T-cell receptor repertoires in HIV-1-infected combination antiretroviral therapy-treated patients despite sustained suppression of viral replication.
abstract: In most HIV-1-infected patients, highly active antiretroviral therapy (HAART) reduces plasma viral load to <50 copies/mL and increases CD4+ T-cell number and function. However, it is still unclear whether alterations of T-cell receptor (TCR) beta-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.
authors.affiliation: Department of Clinical Medicine, University La Sapienza, Rome, Italy. antonello.giovannetti@uniroma1.it
authors.forename: Antonello
authors.initials: A
authors.lastname: Giovannetti
authors.forename: Marina
authors.initials: M
authors.lastname: Pierdominici
authors.forename: Marco
authors.initials: M
authors.lastname: Marziali
authors.forename: Francesca
authors.initials: F
authors.lastname: Mazzetta
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Caprini
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Russo
authors.forename: Roberto
authors.initials: R
authors.lastname: Bugarini
authors.forename: Maria Livia
authors.initials: ML
authors.lastname: Bernardi
authors.forename: Ivano
authors.initials: I
authors.lastname: Mezzaroma
authors.forename: Fernando
authors.initials: F
authors.lastname: Aiuti
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D019674:Genes, T-Cell Receptor beta; D015497:HIV-1; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014766:Viremia / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D006684:HLA-DR Antigens