Immune responses and reconstitution in HIV-1 infected individuals: impact of anti-retroviral therapy, cytokines and therapeutic vaccination.
Most patients with chronic HIV-1 infection lack functional CD4(+) and CD8(+) HIV-1-specific T cells with proliferative and cytolytic capacity, respectively. This is despite being able to produce intracellular cytokines in response to viral antigens. Protease inhibitor (PI)-based highly active anti-retroviral therapy (HAART) is unable to completely eradicate virus and fails to enable total restoration of immunity including induction of anti-HIV-1 responses. We have taken novel approaches towards the treatment of chronic HIV-1 disease with the aim of instigating long-term non-progressor status and depletion of virus reservoirs. HIV-1-specific CD4(+) and CD8(+) T cell responses were measured following the administration of cytokines, during therapeutic vaccination, and following treatment interruption (TI) or drug therapy change. Administration of cytokines, with or without therapeutic vaccination, in HAART treated patients, improved both CD4(+) and CD8(+) HIV-1-specific T cell responses even in late-stage disease. Virus-specific T cell responses were also seen during TI or when transient viraemia was apparent, and following therapy change from a PI- to a non-nucleoside-based HAART regimen. Reconstitution of HIV-1-specific immune responses was found to be transient and reversal to the previous anergic state was rapid. Viral reservoirs in the latently infected resting CD4(+) T cells, on follicular dendritic cells of germinal centers or even in infected thymic epithelium may be involved in clonal suppression and anergy. These may present major obstacles to the maintenance of HIV-1-specific responses and the eventual eradication of HIV-1.
Imami
N
N
Department of Immunology, Imperial College School of Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK. n.imami@ic.ac.uk
Hardy
G
G
Burton
C
C
Pires
A
A
Pido-Lopez
J
J
Moss
R
R
Gazzard
B
B
Gotch
F
F
D016915:AIDS Vaccines / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D016207:Cytokines / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*; D015497:HIV-1; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use; D008213:Lymphocyte Activation; D011994:Recombinant Proteins
D016915:AIDS Vaccines; D016207:Cytokines; D007376:Interleukin-2; D011994:Recombinant Proteins; C105086:remune; D016178:Granulocyte-Macrophage Colony-Stimulating Factor