title: HIV dynamics and T-cell immunity after three structured treatment interruptions in chronic HIV-1 infection.
abstract: OBJECTIVE
  To evaluate whether controlled re-exposures to autologous HIV-1 could boost HIV-specific immunity and limit virus replication in patients with chronic HIV-1 infection.
  
  
  METHODS
  Subjects with at least 2 years virus suppression during antiretroviral therapy and a CD4 : CD8 ratio > 1 were randomly assigned to interrupt highly active antiretroviral treatment (HAART) three times (n = 12) or to continue their previous HAART (n = 14).
  
  
  RESULTS
  In 10/12 interrupter patients a rebound of HIV-1 RNA was detected in all three structured treatment interruptions (STI). Plasma virus doubling time was shorter during the first STI than in the second and third STI, corresponding to an average 13% reduction in viral basic reproductive rate. However, the mean time before plasma viral load rose to > 50 copies/ml was significantly shorter in the second and third STI. The average frequency of HIV-specific CD8 T cells in the interrupter patients at the end of the third STI cycle was significantly higher compared with the baseline and the end of the first STI. A substantial increase in HIV-specific CD8 T cell frequencies was found in four interrupter patients, whereas there were no changes in all 14 non-interrupter individuals. A weak p24-specific T helper response developed in 5/12 interrupter patients compared with no response in non-interruptors, but these responses were transient and disappeared rapidly.
  
  
  CONCLUSIONS
  The increase in the control of viral replication, and positive effects of STI on immune responses in this population should encourage the further development of HIV-specific immune-based therapeutic strategies.
authors: Retrovirology Laboratory, IrsiCaixa Foundation and HIV Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. lruiz@ns.hugtip.scs.es
authors: L
authors: L
authors: Ruiz
authors: G
authors: G
authors: Carcelain
authors: J
authors: J
authors: Martínez-Picado
authors: S
authors: S
authors: Frost
authors: S
authors: S
authors: Marfil
authors: R
authors: R
authors: Paredes
authors: J
authors: J
authors: Romeu
authors: E
authors: E
authors: Ferrer
authors: K
authors: K
authors: Morales-Lopetegi
authors: B
authors: B
authors: Autran
authors: B
authors: B
authors: Clotet
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D002908:Chronic Disease; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019562:Viral Load
chemical_list: D007376:Interleukin-2; D007371:Interferon-gamma