Immunological and virological efficacy of a therapeutic immunization combined with interleukin-2 in chronically HIV-1 infected patients.
OBJECTIVE
Several lines of evidence suggest that the immune system may control HIV-1 replication, but that it could fail in the long term. Strategies aimed to elicit specific immune responses may enable patients to contain virus replication.


METHODS
HIV-1-infected patients were randomized to continue either their antiviral therapy alone (controls; n = 37) or with four boosts of vaccination combining ALVAC-HIV (vCP1433) and Lipo-6T vaccines (weeks 0, 4, 8, 12) followed by three cycles of subcutaneous interleukin-2 (weeks 16, 24, 32) (Vac-IL-2 group; n = 34).


RESULTS
Of the Vac-IL-2 group, 15/32 (47%) exhibited a stable HIV p24 antigen-proliferative response compared with 8/33 (24%) controls (P = 0.049). After vaccination, 19/33 (58%) of the Vac-IL-2 group exhibited a multiepitopic HIV-1-specific CD4 cell proliferative response compared with 9/36 (25%) of controls (P = 0.006). The breadth and the magnitude of HIV-specific interferon-gamma-producing CD8 T cells improved in the Vac-IL-2 group. After stopping antiviral drugs, 24% of the Vac-IL-2 group lowered their viral set point compared with 5% of controls (P = 0.027). Logistic-regression analysis demonstrated that vaccine-elicited immunological responses were predictive of virological control (P = 0.046 and 0.014 for stable and multiepitopic CD4 T cell responses, respectively).


CONCLUSIONS
This study provides proof of the concept that therapeutic immunization before antiviral drug cessation may contribute to the containment of HIV replication.
Lévy
Yves
Y
Unité d'Immunologie Clinique, Hôpital Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil Cedex, Paris, France. yves.levy@hmn.ap-hop-paris.fr
Gahéry-Ségard
Hanne
H
Durier
Christine
C
Lascaux
Anne-Sophie
AS
Goujard
Cécile
C
Meiffrédy
Vincent
V
Rouzioux
Christine
C
El Habib
Raphaëlle
R
Beumont-Mauviel
Maria
M
Guillet
Jean-Gérard
JG
Delfraissy
Jean-François
JF
Aboulker
Jean-Pierre
JP
D016915:AIDS Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000276:immunology; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000627:therapeutic use; D017778:Vaccines, Combined / Q000627:therapeutic use; D019562:Viral Load; D014765:Viral Vaccines / Q000009:adverse effects / Q000627:therapeutic use
D016915:AIDS Vaccines; C078788:ALVAC vaccine; D015488:HIV Antigens; D007376:Interleukin-2; D014613:Vaccines, Attenuated; D017778:Vaccines, Combined; D014765:Viral Vaccines; D007371:Interferon-gamma