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). CONCLUSION: This study provides proof of the concept that therapeutic immunization before antiviral drug cessation may contribute to the containment of HIV replication.
RCT Entities:
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-infectedpatients 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). CONCLUSION: This study provides proof of the concept that therapeutic immunization before antiviral drug cessation may contribute to the containment of HIV replication.
Authors: Lucy Dorrell; Hongbing Yang; Beatrice Ondondo; Tao Dong; Kati di Gleria; Annie Suttill; Christopher Conlon; Denise Brown; Patricia Williams; Paul Bowness; Nilu Goonetilleke; Tim Rostron; Sarah Rowland-Jones; Tomás Hanke; Andrew McMichael Journal: J Virol Date: 2006-05 Impact factor: 5.103
Authors: Antonio Valentin; Agneta von Gegerfelt; Margherita Rosati; Georgios Miteloudis; Candido Alicea; Cristina Bergamaschi; Rashmi Jalah; Vainav Patel; Amir S Khan; Ruxandra Draghia-Akli; George N Pavlakis; Barbara K Felber Journal: Vaccine Date: 2010-02-23 Impact factor: 3.641
Authors: Erin E West; Hyun-Tak Jin; Ata-Ur Rasheed; Pablo Penaloza-Macmaster; Sang-Jun Ha; Wendy G Tan; Ben Youngblood; Gordon J Freeman; Kendall A Smith; Rafi Ahmed Journal: J Clin Invest Date: 2013-05-15 Impact factor: 14.808
Authors: Brian O Porter; Kara B Anthony; Jean Shen; Barbara Hahn; Chris E Keh; Frank Maldarelli; William C Blackwelder; Henry Clifford Lane; Joseph A Kovacs; Richard T Davey; Irini Sereti Journal: AIDS Date: 2009-01-14 Impact factor: 4.177
Authors: Cara C Wilson; Mark J Newman; Brian D Livingston; Samantha MaWhinney; Jeri E Forster; Jim Scott; Robert T Schooley; Constance A Benson Journal: Clin Vaccine Immunol Date: 2008-04-09