title: The presence of anti-Tat antibodies in HIV-infected individuals is associated with containment of CD4+ T-cell decay and viral load, and with delay of disease progression: results of a 3-year cohort study.
abstract: BACKGROUND
  Tat is a key HIV-1 virulence factor, which plays pivotal roles in virus gene expression, replication, transmission and disease progression. After release, extracellular Tat accumulates in tissues and exerts effects on both the virus and the immune system, promoting immune activation and virus spreading while disabling the host immune defense. In particular, Tat binds Env spikes on virus particles forming a virus entry complex, which favors infection of dendritic cells and efficient transmission to T cells via RGD-binding integrins. Tat also shields the CCR5-binding sites of Env rendering ineffective virus neutralization by anti-Env antibodies (Abs). This is reversed by the anti-Tat Abs present in natural infection or induced by vaccination.
  
  
  RESULTS
  Here we present the results of a cohort study, showing that the presence of anti-Tat Abs in asymptomatic and treatment-naïve HIV-infected subjects is associated with containment of CD4+ T-cell loss and viral load and with a delay of disease progression. In fact, no subjects with high anti-Tat Ab titers initiated antiretroviral therapy during the three years of follow-up. In contrast, no significant effects were seen for anti-Env and anti-Gag Abs. The increase of anti-Env Ab titers was associated with a reduced risk of starting therapy only in the presence of anti-Tat Abs, suggesting an effect of combined anti-Tat and anti-Env Abs on the Tat/Env virus entry complex and on virus neutralization.
  
  
  CONCLUSIONS
  Anti-Tat immunity may help delay HIV disease progression, thus, targeting Tat may offer a novel therapeutic intervention to postpone antiretroviral treatment or to increase its efficacy.
authors: Stefania
authors: S
authors: Bellino
authors: Antonella
authors: A
authors: Tripiciano
authors: Orietta
authors: O
authors: Picconi
authors: Vittorio
authors: V
authors: Francavilla
authors: Olimpia
authors: O
authors: Longo
authors: Cecilia
authors: C
authors: Sgadari
authors: Giovanni
authors: G
authors: Paniccia
authors: Angela
authors: A
authors: Arancio
authors: Gioacchino
authors: G
authors: Angarano
authors: Nicoletta
authors: N
authors: Ladisa
authors: Adriano
authors: A
authors: Lazzarin
authors: Giuseppe
authors: G
authors: Tambussi
authors: Silvia
authors: S
authors: Nozza
authors: Carlo
authors: C
authors: Torti
authors: Emanuele
authors: E
authors: Focà
authors: Guido
authors: G
authors: Palamara
authors: Alessandra
authors: A
authors: Latini
authors: Laura
authors: L
authors: Sighinolfi
authors: Francesco
authors: F
authors: Mazzotta
authors: Massimo
authors: M
authors: Di Pietro
authors: Giovanni
authors: G
authors: Di Perri
authors: Stefano
authors: S
authors: Bonora
authors: Vito S
authors: VS
authors: Mercurio
authors: Cristina
authors: C
authors: Mussini
authors: Andrea
authors: A
authors: Gori
authors: Massimo
authors: M
authors: Galli
authors: Paolo
authors: P
authors: Monini
authors: Aurelio
authors: A
authors: Cafaro
authors: Fabrizio
authors: F
authors: Ensoli
authors: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy. barbara.ensoli@iss.it.
authors: Barbara
authors: B
authors: Ensoli
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015686:Gene Products, env / Q000276:immunology; D015752:Genes, env / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D019562:Viral Load; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015686:Gene Products, env; D054322:tat Gene Products, Human Immunodeficiency Virus